UNASSIGNED: To assess leukemia risk in occupational populations exposed to low levels of benzene.
UNASSIGNED: Leukemia incidence data from the Chinese Benzene Cohort Study were fitted using the Linearized multistage (LMS) model. Individual benzene exposure levels, urinary S-phenylmercapturic acid (S-PMA) and trans, trans-muconic acid (t, t-MA) were measured among 98 benzene-exposed workers from factories in China. Subjects were categorized into four groups by rounding the quartiles of cumulative benzene concentrations (< 3, 3-5, 5-12, ≥12 mg/m3·year, respectively). The risk of benzene-induced leukemia was assessed using the LMS model, and the results were validated using the EPA model and the Singapore semi-quantitative risk assessment model.
UNASSIGNED: The leukemia risks showed a positive correlation with increasing cumulative concentration in the four exposure groups (excess leukemia risks were 4.34, 4.37, 4.44 and 5.52 × 10-4, respectively; Ptrend < 0.0001) indicated by the LMS model. We also found that the estimated leukemia risk using urinary t, t-MA in the LMS model was more similar to those estimated by airborne benzene compared to S-PMA. The leukemia risk estimated by the LMS model was consistent with both the Singapore semi-quantitative risk assessment model at all concentrations and the EPA model at high concentrations (5-12, ≥12 mg/m3·year), while exceeding the EPA model at low concentrations (< 3 and 3-5 mg/m3·year). However, in all four benzene-exposed groups, the leukemia risks estimated by these three models exceeded the lowest acceptable limit for carcinogenic risk set by the EPA at 1 × 10-6.
UNASSIGNED: This study demonstrates the utility of the LMS model derived from the Chinese benzene cohort in assessing leukemia risk associated with low-level benzene exposure, and suggests that leukemia risk may occur at cumulative concentrations below 3 mg/m3·year.

Harness® is a commercial herbicide that contains acetochlor at a concentration of 84% as an active ingredient. Ubiquitous, persistent, and substantial uses of Harness® in agricultural processes have resulted in the pollution of nearby water sources, posing a threat to various aquatic biotas, including fish. The effects of Harness® toxicity on fish health are little known. So, this study aimed to describe the impact of herbicide Harness® on the oxidative stress and reproductive and thyroid performance of male and female tilapia (Oreochromis niloticus) and also investigate the prospective role of the natural antioxidant lycopene supplementation in dismissing the adverse properties of Harness®. Antioxidant enzyme (catalase, superoxide dismutase, and total antioxidant capacity) and hormone measurements (T, E2, T3, and T4) were carried out, and gonadal and thyroid follicle histological sections were examined as a method to investigate the effects of Harness® toxicity on fish. Male and female tilapia were exposed to 10 μmol/L and 100 μmol/L of Harness® and treated with 10 mg lycopene/kg for 15 days of exposure. Our results demonstrated that the antioxidant enzyme activity was altered by Harness exposure and serum T for both males and females dropped; also, female E2 levels decreased, but male E2 increased. Exposure to higher dose of Harness® induced elevation in both T3 and T4 levels, although the low exposure dose stimulated T4 levels. Harness® exposure prompted histological variations and degenerative changes in testicular, ovarian, and thyroid follicle tissues. Lycopene supplement administration diminished oxidative stress induced by Harness®, alleviating its endocrine disparaging effects by neutralizing T3, T4, T, and E2 and ameliorating the histological structure of gonadal and thyroid tissues. In conclusion, lycopene supplementation was preformed to normalize the alterations and oxidative damage caused by Harness® in Nile tilapia, suggesting that lycopene-supplemented diet functioned as potent antioxidants and had the ability to alleviate oxidative stress and thyroid and reproductive toxicity caused by herbicide Harness®. Moreover, it is crucial to take appropriate care when consuming herbicides to defend the aquatic environment.

The lack of T cell infiltrates is a major obstacle to effective immunotherapy in cancer. Conversely, the formation of tumor-associated tertiary-lymphoid-like structures (TA-TLLSs), which are the local site of humoral and cellular immune responses against cancers, is associated with good prognosis, and they have recently been detected in immune checkpoint blockade (ICB)-responding patients. However, how these lymphoid aggregates develop remains poorly understood. By employing single-cell transcriptomics, endothelial fate mapping, and functional multiplex immune profiling, we demonstrate that antiangiogenic immune-modulating therapies evoke transdifferentiation of postcapillary venules into inflamed high-endothelial venules (HEVs) via lymphotoxin/lymphotoxin beta receptor (LT/LTβR) signaling. In turn, tumor HEVs boost intratumoral lymphocyte influx and foster permissive lymphocyte niches for PD1- and PD1+TCF1+ CD8 T cell progenitors that differentiate into GrzB+PD1+ CD8 T effector cells. Tumor-HEVs require continuous CD8 and NK cell-derived signals revealing that tumor HEV maintenance is actively sculpted by the adaptive immune system through a feed-forward loop.

Acute diarrhea is the most frequent diagnosis among ill travelers. Sleep loss may weaken the body\'s defense against pathogens and increase susceptibility to infection. The relationship between sleep and infectious diarrhea has not been studied and was assessed utilizing data from a controlled human infection model (CHIM) for enterotoxigenic Escherichia coli (ETEC).
During a CHIM assessing the efficacy of an immunoprophylactic targeting ETEC against moderate-to-severe diarrhea (MSD) following challenge, we measured sleep via actigraphy over an 8-day inpatient period. We hypothesized better sleep pre-challenge would predict illness symptomatology following challenge.
Among 57 participants (aged 34.4 ± 8.1 years, 64% male), there was no relationship between sleep metrics and incidence of MSD. However, longer total sleep time the night preceding ETEC challenge was associated with lower maximum 24 h diarrhea volume (B = -1.80, p = 0.01) and total diarrhea volume (B = -2.45, p = 0.01).
This novel study showed that shorter sleep duration predicted diarrhea severity over the course of an ETEC infection. Future work should experimentally manipulate sleep to further clarify its impact on diarrhea-related outcomes for ETEC and other important enteric pathogens.

Cell-based immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has revolutionized the treatment of hematological malignancies, especially in patients who are refractory to other therapies. However, there are critical obstacles that hinder the widespread clinical applications of current autologous therapies, such as high cost, challenging large-scale manufacturing, and inaccessibility to the therapy for lymphopenia patients. Therefore, it is in great demand to generate the universal off-the-shelf cell products with significant scalability. Human induced pluripotent stem cells (iPSCs) provide an \"unlimited supply\" for cell therapy because of their unique self-renewal properties and the capacity to be genetically engineered. iPSCs can be differentiated into different immune cells, such as T cells, natural killer (NK) cells, invariant natural killer T (iNKT) cells, gamma delta T (γδ T), mucosal-associated invariant T (MAIT) cells, and macrophages (Mφs). In this review, we describe iPSC-based allogeneic cell therapy, the different culture methods of generating iPSC-derived immune cells (e.g., iPSC-T, iPSC-NK, iPSC-iNKT, iPSC-γδT, iPSC-MAIT and iPSC-Mφ), as well as the recent advances in iPSC-T and iPSC-NK cell therapies, particularly in combinations with CAR-engineering. We also discuss the current challenges and the future perspectives in this field towards the foreseeable applications of iPSC-based immune therapy.

UNASSIGNED: The present research aimed to study the relationship between body mass index (BMI), sex hormones, leptin, and irisin in children and adolescents with different body types.
UNASSIGNED: In this study, a stratified cluster random sampling method was used to select students aged 8-15 years from two 9-year schools as the research subjects. Based on a case-control study, 183 overweight/obese students were selected. After using sex and age matching to create a matched sample of normal-weighted students, a total of 366 students, including 214 boys (58.5%) and 152 girls (41.5%) were included. We measured their height and weight and calculated their body mass index BMI. Afterward, their concentrations of leptin, irisin, oestradiol (E2), and testosterone (T) in the serum were detected.
UNASSIGNED: There were significant differences in T, E2, leptin, and irisin between normal-weighted boys and girls (p < 0.05). There were statistically significant differences in T, E2, and irisin between overweight/obese boys and girls (p < 0.05). Overweight/obese students had higher concentrations of irisin and leptin than normal-weight students (p < 0.05). The direct effect of BMI on irisin was not statistically significant in either normal or overweight/obese students, but their indirect effects via leptin were statistically significant (for normal-weight boys and girls, standardized indirect effect coefficient: 0.29 and 0.38, respectively; for overweight/obese boys and girls, standardized indirect effect coefficient: 0.36 and 0.34, respectively). There was a negative pathway of E2 → leptin → irisin in normal-weight boys (standardized indirect effect coefficient: -0.24) and a negative pathway of T → leptin → irisin in overweight/obese boys (standardized indirect effect coefficient: -0.27).
UNASSIGNED: The indirect effects of BMI on irisin via leptin exist in children and adolescents of different body types. E2 was negatively correlated with leptin in normal-weight boys, whereas T was negatively correlated with leptin in overweight/obese boys.

T is the founding member of the T-box family of transcription factors; family members are critical for cell fate decisions and tissue morphogenesis throughout the animal kingdom. T is expressed in the primitive streak and notochord with mouse mutant studies revealing its critical role in mesoderm formation in the primitive streak and notochord integrity. We previously demonstrated that misexpression of Tbx6 in the paraxial and lateral plate mesoderm results in embryos resembling Tbx15 and Tbx18 nulls. This, together with results from in vitro transcriptional assays, suggested that ectopically expressed Tbx6 can compete with endogenously expressed Tbx15 and Tbx18 at the binding sites of target genes. Since T-box proteins share a similar DNA binding domain, we hypothesized that misexpressing T in the paraxial and lateral plate mesoderm would also interfere with the endogenous Tbx15 and Tbx18, causing embryonic phenotypes resembling those seen upon Tbx6 expression in the somites and limbs. Interestingly, ectopic T expression led to distinct embryonic phenotypes, specifically, reduced-sized somites in embryos expressing the highest levels of T, which ultimately affects axis length and neural tube morphogenesis. We further demonstrate that ectopic T leads to ectopic expression of Tbx6 and Mesogenin 1, known targets of T. These results suggests that ectopic T expression contributes to the phenotype by activating its own targets rather than via a straight competition with endogenous T-box factors.

Prostate cancer (PCa) is the most common non-cutaneous cancer in men in Europe and is predicted to exhibit declining mortality in the European Union (EU) due to various recent improvements in treatment. The goal of this short review is to give insight into the European treatment landscape of PCa, while focusing on improvements in care.

Human herpesvirus 6 (HHV-6) reactivation can occur in patients who are highly immunosuppressed, including those who have undergone hematopoietic stem cell transplantation (HSCT). HHV-6 encephalitis is a severe manifestation that is well described in the HSCT population. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel cancer-directed immunotherapy that results in severe immunosuppression. Patients undergoing CAR-T therapy may be at risk for HHV-6 encephalitis, which can be difficult to distinguish from a common adverse effect of CAR-T therapy, neurotoxicity. Herein, we describe 2 patients diagnosed with HHV-6 encephalitis after CAR-T therapy and discuss the diagnostic approach and differential diagnosis for altered mental status after CAR-T therapy. Diagnosing HHV-6 encephalitis can be difficult in this patient population as altered mental status is common after CAR-T therapy and may be attributed to CAR-T-associated neurotoxicity.

Schuurs-Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopmental disorder is a rare disorder characterized by intellectual disability, abnormal craniofacial features and congenital malformations. SHMS is an autosomal dominant hereditary disease caused by pathogenic variants in the PACS1 gene. PACS1 is a trans-Golgi-membrane traffic regulator that directs protein cargo and several viral envelope proteins. It is upregulated during human embryonic brain development and has low expression after birth. So far, only 54 patients with SHMS have been reported. In this work, we report on seven new identified SHMS individuals with the classical c.607C > T: p.Arg206Trp PACS1 pathogenic variant and review clinical and molecular aspects of all the patients reported in the literature, providing a summary of clinical findings grouped as very frequent (≥75% of patients), frequent (50-74%), infrequent (26-49%) and rare (less than ≤25%).