UNASSIGNED: This study aimed to evaluate changes in ocular surface parameters among obstructive sleep apnea syndrome (OSAS) patients.
UNASSIGNED: 44 healthy volunteers (88 eyes) and 27 OSAS patients (54 eyes) were recruited in our cross-sectional study. 14 patients were classified as mild&moderate OSAS, and 13 patients were classified as severe OSAS. For evaluating the ocular surface, the following tests were conducted: the height of tear meniscus (TMH), first non-invasive tear break-up time (FNITBUT), mean non-invasive tear break-up time (MNITBUT), the score of Meibomian gland dropout area (Meiboscore), the tear test of anesthesia-free Schirmer I (SIT), corneal fluorescein staining (CFS), partial blinks rate (PBR), the lipid layer thickness (LLT), ocular surface disease index (OSDI). The results obtained from the study were analyzed and compared among the groups.
UNASSIGNED: FNITBUT, MNITBUT, and TMH were lower. OSDI, CFS, Meiboscore and PBR were higher in the OSAS group than those in the control group. The mild&moderate as well as the severe OSAS subgroups had statistically significantly lower TMH, and higher OSDI and PBR than the control group. Meanwhile, we found there were no significant differences between two OSAS subgroups. CFS was higher in the severe OSAS group than the mild&moderate OSAS group. Significantly lower FNITBUT, MNITBUT and higher Meiboscore were observed in the severe OSAS subgroup than in the control group, and MNITBUT was higher in severe OSAS objects than in the mild&moderate OSAS objects. LLT and SIT did not exhibit significant differences among control and OSAS subgroups. FNITBUT and MNITBUT showed significantly negative correlations with BMI, while Meiboscore showed a significant positive correlation with AHI.
UNASSIGNED: Patients with OSAS have a tendence of dry eyes, whereas control subjects do not. This indicates us that the OSAS patients should pay more attention to ocular surface care.

Translocator protein (TSPO) is a neuroinflammation hallmark. Different TSPO affinity compounds have been produced and over time, the techniques of radiolabeling have been refined. The aim of this systematic review is to summarize the development of new radiotracers for dementia and neuroinflammation imaging.
An online search of the literature was conducted in the PubMed, Scopus, Medline, Cochrane Library, and Web of Science databases, selecting published studies from January 2004 to December 2022. The accepted studies considered the synthesis of TSPO tracers for nuclear medicine imaging in dementia and neuroinflammation.
A total of 50 articles was identified. Twelve papers were selected from the included studies\' bibliographies and 34 were excluded. Thus, 28 articles were ultimately selected for quality assessment.
Huge efforts in developing specific and stable tracers for PET/SPECT imaging have been made. The long half-life of 18F makes this isotope a preferable choice to 11C. An emerging limitation to this however is that neuroinflammation involves all of the brain which inhibits the possibility of detecting a slight inflammation status change in patients. A partial solution to this is using the cerebellum as a reference region and developing higher TSPO affinity tracers. Moreover, it is necessary to consider the presence of distomers and racemic compounds interfering with pharmacological tracers\' effects and increasing the noise ratio in images.

The 18 kDa translocator protein (TSPO/PBR) is a multifunctional evolutionary highly conserved outer mitochondrial membrane protein. Decades of research has reported an obligatory role of TSPO/PBR in both mitochondrial cholesterol transport and, thus, steroid production. However, the strict dependency of steroidogenesis on TSPO/PBR has remained controversial. The aim of this study was to provide insight into the steroid profile in complete C57BL/6-Tspotm1GuWu(GuwiyangWurra)-knockout male mice (TSPO-KO) under basal conditions. The steroidome in the brain, adrenal glands, testes and plasma was measured by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS). We found that steroids present in wild-type (WT) mice were also detected in TSPO-KO mice, including pregnenolone (PREG), progestogens, mineralo-glucocorticosteroids and androgens. The concentrations of PREG and most metabolites were similar between genotypes, except a significant decrease in the levels of the 5α-reduced metabolites of progesterone (PROG) in adrenal glands and plasma and of the 5α-reduced metabolites of corticosterone (B) in plasma in TSPO-KO compared to WT animals, suggesting other regulatory functions for the TSPO/PBR. The expression levels of the voltage-dependent anion-selective channel (VDAC-1), CYP11A1 and 5α-reductase were not significantly different between both groups. Thus, the complete deletion of the tspo gene in male mice does not impair de novo steroidogenesis in vivo.

Human-caused mortality of wildlife is a pervasive threat to biodiversity. Assessing the population-level impact of fisheries bycatch and other human-caused mortality of wildlife has typically relied upon deterministic methods. However, population declines are often accelerated by stochastic factors that are not accounted for in such conventional methods. Building on the widely applied potential biological removal (PBR) equation, we devised a new population modeling approach for estimating sustainable limits to human-caused mortality and applied it in a case study of bottlenose dolphins affected by capture in an Australian demersal otter trawl fishery. Our approach, termed sustainable anthropogenic mortality in stochastic environments (SAMSE), incorporates environmental and demographic stochasticity, including the dependency of offspring on their mothers. The SAMSE limit is the maximum number of individuals that can be removed without causing negative stochastic population growth. We calculated a PBR of 16.2 dolphins per year based on the best abundance estimate available. In contrast, the SAMSE model indicated that only 2.3-8.0 dolphins could be removed annually without causing a population decline in a stochastic environment. These results suggest that reported bycatch rates are unsustainable in the long term, unless reproductive rates are consistently higher than average. The difference between the deterministic PBR calculation and the SAMSE limits showed that deterministic approaches may underestimate the true impact of human-caused mortality of wildlife. This highlights the importance of integrating stochasticity when evaluating the impact of bycatch or other human-caused mortality on wildlife, such as hunting, lethal control measures, and wind turbine collisions. Although population viability analysis (PVA) has been used to evaluate the impact of human-caused mortality, SAMSE represents a novel PVA framework that incorporates stochasticity for estimating acceptable levels of human-caused mortality. It offers a broadly applicable, stochastic addition to the demographic toolbox to evaluate the impact of human-caused mortality on wildlife.
La mortalidad de la fauna causada por humanos es una amenaza continua para la biodiversidad. El análisis del impacto a nivel poblacional de la captura pesquera incidental y otras causas humanas de la mortalidad de la fauna comúnmente ha dependido de métodos determinísticos. Sin embargo, las declinaciones poblacionales con frecuencia se aceleran por los factores estocásticos que no son considerados en dichos métodos convencionales. A partir de la ecuación de extirpación biológica potencial (EBP) de extensa aplicación diseñamos una nueva estrategia de modelación poblacional para estimar los límites sustentables de la mortalidad causada por humanos y la aplicamos en un estudio de caso de los delfines nariz de botella afectados por la captura en una pesquería australiana de arrastre demersal. Nuestra estrategia, denominada mortalidad antropogénica sustentable en ambientes estocásticos (MASAM) incorpora la estocasticidad ambiental y demográfica, incluyendo la dependencia que tienen las crías por sus madres. El límite MASAM es el número máximo de individuos que pueden extirparse sin causar un crecimiento poblacional estocástico negativo. Calculamos un EBP de 16.3 delfines por año con base en la mejor estimación de abundancia disponible. Como contraste, el modelo MASAM indicó que sólo podían extirparse entre 2.3 y 8.0 delfines anualmente sin ocasionar una declinación poblacional en un ambiente estocástico. Estos resultados sugieren que las tasas reportadas de captura incidental no son sustentables a largo plazo, a menos que las tasas reproductivas sean sistemáticamente más altas que el promedio. La diferencia entre el cálculo determinístico del EBP y los límites de MASAM mostró que los enfoques determinísticos pueden subestimar el verdadero impacto de la mortalidad de la fauna causada por humanos. Lo anterior resalta la importancia de integrar la estocasticidad al evaluar el impacto de la captura incidental y otras causas humanas de la mortalidad como la caza, las medidas letales de control y las colisiones con turbinas de viento. Aunque el análisis de viabilidad poblacional (AVP) se ha utilizado para evaluar el impacto de la mortalidad causada por humanos, MASAM representa un marco novedoso de AVP que incorpora la estocasticidad para estimar los niveles aceptables de mortalidad causada por humanos. Este enfoque ofrece una adición estocástica de aplicación generalizada para las herramientas demográficas usadas para evaluar el impacto de la mortalidad causada por humanos sobre la fauna.
在不断变化的情景下估计野生动物死亡率的持续性限度的随机模型 人类造成的野生动物死亡是对生物多样性的普遍威胁。目前, 通常依赖于确定性方法来评估渔业副渔获物和其它人为造成的野生动物死亡在种群水平上的影响。然而, 随机因素往往会加速种群数量的下降, 但这种常规方法没有将其纳入考虑。我们在已得到广泛应用的生物可移除潜在量(Potential Biological Removal, PBR)方程的基础上, 设计了一种新的种群建模方法来估计人为造成的死亡的可持续限度, 并将其应用于澳大利亚底层拖网渔业中受影响的瓶鼻海豚的案例研究。我们的方法可以称为“随机环境中的可持续人为影响死亡率(SAMSE)”, 包含了环境和种群的随机性, 还包括了后代对母亲的依赖性。SAMSE的极限是指在不引起负面的种群随机增长的情况下可以移除的最大个体数。我们根据现有最佳的丰度估计, 计算出海豚的生物可移除潜在量为每年16.2头。相比之下, SAMSE模型则显示, 在随机环境中, 为了不引起种群下降, 每年只能移除2.3至8.0头海豚。这些结果表明, 除非繁殖率持续高于平均水平, 否则长期来看报告的副渔获率是不可持续的。确定性的PBR计算和SAMSE限制之间的差异表明, 确定性方法可能低估了人为造成野生动物死亡的真实影响。这突出了整合随机性在评估副渔获或其它人为造成的死亡(如狩猎、灭杀控制措施和风力涡轮机碰撞)对野生动物的影响中的重要性。尽管种群生存力分析(PVA)已被用于评估人为造成死亡的影响, 但SAMSE代表了一个包含随机性的PVA新框架, 可以用于估计人为造成死亡的可接受水平。它为种群统计学工具补充了一种广泛适用的随机性方法, 以评估人类造成的死亡对野生动物的影响。【翻译:胡怡思;审校:聂永刚】.

BACKGROUND: This is a prospective cohort study of partial breast reconstruction (PBR) with a lateral chest wall perforator flap (LCWPF) to facilitate breast conservation surgery (BCS) for women undergoing surgery for breast cancer. The study was undertaken to study the clinical and cancer outcomes.
METHODS: Patients diagnosed with ductal carcinoma in situ (DCIS) or breast cancer who consented to undergo BCS with PBR with LCWPF were included in the study. A prospective database has been maintained to collect information on clinico-pathological features, complications, and follow-up. Patients were asked to complete an anonymised PROM questionnaire over the years. The hospital electronic records were interrogated for women who have completed 5 years follow-up to assess for development of recurrence/events.
RESULTS: A total of 105 patients underwent PBR with LCWPFs between 2011 and 2018. Of these, 74% underwent cancer resection and PBR as one operation whilst 26% underwent PBR as a two-stage approach. The median tumor size on pre-op imaging was 30 mm for the one-stage approach and 39.5 mm for the two-stage approach (p-value=0.003). The complication rates were low and the re-operation rate for close margins was 10%, with 4% eventually requiring mastectomy. Good-to-excellent esthetic outcomes were reported in more than 80% of cases by patients and clinicians. The local recurrence rate (LR) was 2%, distant recurrence rate 10.5%, disease free survival (DFS) 86%, distant disease-free survival (DDFS) 89% and overall survival (OS) 94.8% at 4.5 years median follow-up. This procedure provides an effective oncological approach, avoiding mastectomy with a good-to-excellent cosmetic outcome. The follow-up data establishes the safety of this approach.
CONCLUSIONS: This is the first published series of recurrence and survival data in patients undergoing PBR. We intend to continue with data collection to assess long-term outcomes beyond 10 years. The authors would recommend consideration of this technique to facilitate BCS and avoid mastectomy.
BACKGROUND: Not applicable.

This paper presents a description of recent research and the multi-target tracking in experimental passive bistatic radar (PBR) system taking advantage of numerous non-cooperative AM radio signals via multi-static doppler shifts. However, it raises challenges for use by multiple spatially distributed AM radio illuminators for multi-target tracking in PBR system due to complex data association hypotheses and no directly used tracking algorithm in the practical scenario. To solve these problems, after a series of key array signal processing techniques in the self-developed system, by constructing a nonlinear measurement model, the novel method is proposed to accommodate nonlinear model by using the unscented transformation (UT) in Gaussian mixture (GM) implementation of iterated-corrector cardinality-balanced multi-target multi-Bernoulli (CBMeMBer). Simulation and experimental results analysis verify the feasibility of this approach used in a practical PBR system for moving multi-target tracking.

Swine leukocyte antigen (SLA) plays a central role in controlling the immune response by discriminating self and foreign antigens and initiating an immune response. Studies on SLA polymorphism have demonstrated associations between SLA allelic variants, immune response, and disease resistance. The SLA polymorphism is due to host-pathogen co-evolution resulting in improved adaptation to diverse environments making SLA a crucial genomic region for comparative diversity studies. Although locally-adapted African pigs have small body sizes, they possess increased resilience under harsh environmental conditions and robust immune systems with reported tolerance to some diseases, including African swine fever. However, data on the SLA diversity in these pigs are not available. We characterized the SLA of unrelated locally-adapted domestic pigs from Homa Bay, Kenya, alongside exotic pigs and warthogs. We undertook SLA comparative diversity of the functionally expressed SLA class I (SLA-1, SLA-2) and II (DQB1) repertoires in these three suids using the reverse transcription polymerase chain reaction (RT-PCR) sequence-based typing (SBT) method. Our data revealed higher genetic diversity in the locally-adapted pigs and warthogs compared to the exotic pigs. The nucleotide substitution rates were higher in the peptide-binding regions of the SLA-1, SLA-2, and DQB1 loci, indicative of adaptive evolution. We obtained high allele frequencies in the three SLA loci, including some breed-specific private alleles, which could guide breeders to increase their frequency through selection if confirmed to be associated with enhanced resilience. Our study contributes to the growing body of knowledge on genetic diversity in free-ranging animal populations in their natural environment, availing the first DQB1 gene data from locally-adapted Kenyan pigs.

BACKGROUND: The translocator protein 18 kDa is recognised as an important biomarker for neuroinflammation due to its soaring expression in microglia. This process is common for various neurological disorders. DPA-714 is a potent TSPO-specific ligand which found its use in Positron Emission Tomography following substitution of fluorine-19 with fluorine-18, a positron-emitting radionuclide. [18F]DPA-714 enables visualisation of inflammatory processes in vivo non-invasively. Radiolabelling of this tracer is well described in literature, including validation for clinical use. Here, we report significant enhancements to the process which resulted in the design of a fully GMP-compliant robust synthesis of [18F]DPA-714 on a popular cassette-based system, Trasis AllinOne, boosting reliability, throughput, and introducing a significant degree of simplicity.
RESULTS: [18F]DPA-714 was synthesised using the classic nucleophilic aliphatic substitution on a good leaving group, tosylate, with [18F]fluoride using tetraethylammonium bicarbonate in acetonitrile at 100∘C. The process was fully automated on a Trasis AllinOne synthesiser using an in-house designed cassette and sequence. With a relatively small precursor load of 4 mg, [18F]DPA-714 was obtained with consistently high radiochemical yields of 55-71% (n=6) and molar activities of 117-350 GBq/µmol at end of synthesis. With a single production batch, starting with 31-42 GBq of [18F]fluoride, between 13-20 GBq of the tracer can be produced, enabling multi-centre studies.
CONCLUSIONS: To the best of our knowledge, the process presented herein is the most efficient [18F]DPA-714 synthesis, with advantageous GMP compliance. The use of a Trasis AllinOne synthesiser increases reliability and allows rapid training of production staff.

Despite significant evidence that Rac1 is localized to the nucleus, little is known regarding the function and biological significance of nuclear Rac1. Here, we showed that in response to EGF Rac1 was translocated to nuclear speckles and co-localized with the nuclear speckle marker Serine/arginine-rich splicing factor 2 (SRSF2) in Cos-7 cells. We also showed that the nuclear speckle localization of Rac1 was dependent on its T108 phosphorylation and facilitated by Rac1 polybasic region (PBR) that contains a nuclear localization signal and Rac1 GTPase activity. To gain insight into the function of Rac1 in nuclear speckles, we searched for Rac1 binding proteins in the nucleus. We isolated nuclear fraction of HEK 293 cells and incubated with GST-Rac1 and the phosphomimetic GST-Rac1T108E. We identified 463 proteins that were associated with GST-Rac1T108E, but not with GST-Rac1 by LC-MS/MS. Three notable groups of these proteins are: the heterogeneous nuclear ribonucleoproteins (hnRNPs), small nuclear ribonucleoproteins (snRNPs), and SRSFs, all of which are involved in pre-mRNA splicing and associated with nuclear speckles. We further showed by co-immunoprecipitation that Rac1 interacts with SRSF2, hnRNPA1, and U2A\' in response to EGF. The interaction is dependent on T108 phosphorylation and facilitated by Rac1 PBR and GTPase activity. We showed that hnRNPA1 translocated in and out of nucleus in response to EGF in a similar pattern to Rac1. Rac1 only partially colocalized with U2A\' that localizes to the actual splicing sites adjacent to nuclear speckle. Finally, we showed that Rac1 regulated EGF-induced pre-mRNA splicing and this is mediated by T108 phosphorylation. We conclude that in response to EGF, T108 phosphorylated Rac1 is targeted to nuclear speckles, interacts with multiple groups of proteins involved in pre-mRNA splicing, and regulates EGF-induced pre-mRNA splicing.

Polysialic acid (polySia) is an unusual glycan that posttranslational modifies neural cell adhesion molecule (NCAM) proteins in mammalian cells. The up-regulated expression of polySia-NCAM is associated with tumor progression in many metastatic human cancers and in neurocognitive processes. Two members of the ST8Sia family of α2,8-polysialyltransferases (polySTs), ST8Sia II (STX) and ST8Sia IV (PST) both catalyze synthesis of polySia when activated cytidine monophosphate(CMP)-Sialic acid (CMP-Sia) is translocate into the lumen of the Golgi apparatus. Two key polybasic domains in the polySTs, the polybasic region (PBR) and the polysialyltransferase domain (PSTD) areessential forpolysialylation of the NCAM proteins. However, the precise molecular details to describe the interactions required for polysialylation remain unknown. In this study, we hypothesize that PSTD interacts with both CMP-Sia and polySia to catalyze polysialylation of the NCAM proteins. To test this hypothesis, we synthesized a 35-amino acid-PSTD peptide derived from the ST8Sia IV gene sequence and used it to study its interaction with CMP-Sia, and polySia. Our results showed for the PSTD-CMP-Sia interaction,the largest chemical-shift perturbations (CSP) were in amino acid residues V251 to A254 in the short H1 helix, located near the N-terminus of PSTD. However, larger CSP values for the PSTD-polySia interaction were observed in amino acid residues R259 to T270 in the long H2 helix. These differences suggest that CMP-Sia preferentially binds to the domain between the short H1 helix and the longer H2 helix. In contrast, polySia was principally bound to the long H2 helix of PSTD. For the PSTD-polySia interaction, a significant decrease in peak intensity was observed in the 20 amino acid residues located between the N-and C-termini of the long H2 helix in PSTD, suggesting a slower motion in these residues when polySia bound to PSTD. Specific features of the interactions between PSTD-CMP-Sia, and PSTD-polySia were further confirmed by comparing their 800 MHz-derived HSQC spectra with that of PSTD-Sia, PSTD-TriSia (DP 3) and PSTD-polySia. Based on the interactions between PSTD-CMP-Sia, PSTD-polySia, PBR-NCAM and PSTD-PBR, these findingsprovide a greater understanding of the molecular mechanisms underlying polySia-NCAM polysialylation, and thus provides a new perspective for translational pharmacological applications and development by targeting the two polysialyltransferases.