UNASSIGNED: To investigate the efficacy and safety differences between the cisplatin + paclitaxel (TP) and cisplatin + fluorouracil (PF) regimens in combination with or without immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC) first-line treatment and prognostic factors.
UNASSIGNED: We selected the medical records of patients with late stage ESCC admitted to the hospital between 2019 and 2021. Based on the first-line treatment regimen, control groups were divided into chemotherapy plus ICIs (n = 243) and non-ICIs (n = 171), 119 (49%) in the TP + ICIs group, 124 (51%) in the PF + ICIs group, 83 (48.5%) in the TP group, and 88 (51.5%) in the PF group in the control group. We analyzed and compared factors related to efficacy, safety, or response to toxicity and prognosis across four subgroups.
UNASSIGNED: The overall objective response rate (ORR) and disease control rate (DCR) of the TP plus ICIs group were 42.1% (50/119) and 97.5% (116/119), respectively, which were 6.6% and 7.2% higher than those of the PF plus ICIs group. Patients in the TP combined with ICIs group had higher overall survival (OS) and progression-free survival (PFS) than those in the PF combined with ICIs group [hazard ratio (HR) = 1.702, 95% confidence interval (CI): 0.767-1.499, p = 0.0167 and HR = 1.158, 95% CI: 0.828-1.619, p = 0.0055] ORR and DCR were 15.7% (13/83) and 85.5% (71/83) in the TP chemotherapy alone group, significantly higher than the PF group [13.6% (12/88) and 72.2% (64/88)] (p < 0.05), OS and PFS were also better in patients treated with TP regimen chemotherapy than PF (HR = 1.173, 95% CI: 0.748-1.839, p = 0.0014 and HR = 0.1.245, 95% CI: 0.711-2.183, p = 0.0061). Furthermore, following the combination of TP and PF diets with ICIs, the OS of the patients was higher than that of the group treated with chemotherapy alone (HR = 0.526, 95% CI: 0.348-0.796, p = 0.0023 and HR = 0.781, 95% CI: 0.0.491-1.244, p < 0.001). Regression analysis showed that the neutrophil-to-lymphocyte ratio (NLR), the control nuclear status score (CONUT), and the systematic immune inflammation index (SII) were independent prognostic factors for the efficacy of immunotherapy (p < 0.05). The overall incidence of treatment-associated adverse events (TRAEs) was 79.4% (193/243) and 60.8% (104/171) in the experimental and control groups, respectively, and there was no statistically significant difference in TRAEs between TP + ICIs (80.6%) and PF + ICIs (78.2%) (61.4%) and PF groups (60.2%) (p > 0.05). Overall, 21.0% (51/243) of patients in the experimental group experienced immune-related adverse events (irAEs), and all of these adverse effects were tolerated or remitted following drug treatment without affecting follow-up.
UNASSIGNED: The TP regimen was associated with better PFS and OS with or without ICIs. Furthermore, high CONUT scores, high NLR ratios, and high SII were found to be associated with poor prognosis in combination immunotherapy.

Antimicrobial peptides (AMPs) have attracted extensive attention because of their broad-spectrum antibacterial activity and low level of induced bacterial resistance. However, the development of some natural AMPs does not consider the perfect balance of structural characteristics, resulting in some empirical and controversial practices still existing. To further explore and complete the relationship between parameters and function of α-helix peptide, in this study, the natural antimicrobial peptide TP secreted from Bacillus strain of Tibetan pigs was selected as a template to investigate the effect of systematic mutations in the hydrogen bond formation site of the α-helical antimicrobial peptide on the activity and cell selectivity of the antimicrobial peptide. The target peptide TP(i+4) 1&2&5 with modification of two pairs of positively charged amino acids and a pair of hydrophobic amino acids showed excellent antibacterial ability and the best selectivity index (SI = 64) in vitro. At the same time, TP(i+4) 1&2&5 remained active in the presence of physiological salts and serum. The results of fluorescence, flow cytometry, and electron microscopy showed that the optimized sequences showed good antibacterial activity by membrane infiltration and membrane destruction. The potential of TP(i+4) 1&2&5 in vivo was tested in a mouse peritonitis model. Organ bacterial loads in the liver, kidney, spleen, and lungs of mice treated with TP(i+4) 1&2&5 were significantly lower compared to the infected group (p < 0.05). Overall, these findings contribute to the design and optimization of antimicrobial peptides with high activity and low toxicity and may accelerate the clinical application of antimicrobial peptides.

Erhai Lake is the second largest freshwater lake in Yunnan Province but suffers from the deterioration of water quality and agricultural non-point source pollution (ANPSP). However, little is known about the influence of ANPSP on the water quality of Erhai Lake. The export coefficient model (ECM) was used to obtain the total nitrogen (TN) and total phosphorus (TP) loads from ANPSP in Erhai Lake Basin (ELB). The trophic status of Erhai Lake as influenced by such sources of nutrient input was also been assessed. Results indicated that the TN and TP loads in ELB increased from 1985 to 2005 due to sustainable agricultural development; thereafter, the TN and TP loads decreased from 2005 to 2020, indicating that agricultural pollution prevention improved in ELB. The northern part of ELB had higher pollution intensity than the southern part and the central part, indicating that the ecosystem in the northern part of ELB appeared to be vulnerable. Driving force analysis showed that cattle breeding was the main reason for the exported TN loads in most watersheds, and intensive agricultural planting was the major contributor to TP loads. The mean annual Chl-a concentration had a strong correlation with the TN and TP loads exported from north of ELB, and this finding suggested that ANPSP could lead to eutrophication. The results of this study demonstrate the impacts of agricultural activities on water quality at the watershed scale and provide a scientific foundation for lake management decision-making.

BACKGROUND: Although cisplatin-based chemotherapy has been used as the first-line treatment for ovarian cancer (OC), tumor cells develop resistance to cisplatin during treatment, causing poor prognosis in OC patients. Studies have demonstrated that overactivation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is involved in tumor chemoresistance and that overexpression of microRNA-497 (miR497) may overcome OC chemotherapy resistance by inhibiting the mTOR pathway. However, the low transcriptional efficiency and unstable chemical properties of miR497 limit its clinical application. Additionally, triptolide (TP) was confirmed to possess a superior killing effect on cisplatin-resistant cell lines, partially through inhibiting the mTOR pathway. Even so, the clinical applications of TP are restricted by serious systemic toxicity and weak water solubility.
RESULTS: Herein, whether the combined application of miR497 and TP could further overcome OC chemoresistance by synergically suppressing the mTOR signaling pathway was investigated. Bioinspired hybrid nanoparticles formed by the fusion of CD47-expressing tumor exosomes and cRGD-modified liposomes (miR497/TP-HENPs) were prepared to codeliver miR497 and TP. In vitro results indicated that the nanoparticles were efficiently taken up by tumor cells, thus significantly enhancing tumor cell apoptosis. Similarly, the hybrid nanoparticles were effectively enriched in the tumor areas and exerted significant anticancer activity without any negative effects in vivo. Mechanistically, they promoted dephosphorylation of the overactivated PI3K/AKT/mTOR signaling pathway, boosted reactive oxygen species (ROS) generation and upregulated the polarization of macrophages from M2 to M1 macrophages.
CONCLUSIONS: Overall, our findings may provide a translational strategy to overcome cisplatin-resistant OC and offer a potential solution for the treatment of other cisplatin-resistant tumors.

OBJECTIVE: This study was aimed at exploring the effects of hepatitis B envelope antigen (HBeAg) status on the cellular immune function of patients with hepatitis B virus/treponema pallidum (HBV/TP) co-infection.
METHODS: The clinical data of 79 patients with HBV/TP co-infection admitted to our hospital from January 2019 to January 2020 were retrospectively analyzed. These patients were divided into two groups according to the different HBeAg statuses before the treatment: 41 HBeAg+ patients were included in the HBeAg+ group, while 38 HBeAg- patients were included in the HBeAg- group. The levels of HBV-DNA, T lymphocyte subsets represented by NK cells and cytokines associated with T cells in the peripheral blood (PB) of the patients were compared between both groups.
RESULTS: The HBV-DNA levels in the HBeAg+ group were significantly higher than those in the HBeAg- group (P < 0.05). The levels of CD3+, CD4+, CD4+/CD8+ and natural killer (NK) cells in the HBeAg+ group were higher than those in the HBeAg- group (P < 0.05), while the levels of CD8+ cells were lower than those in the HBeAg- group (P < 0.05). Moreover, the levels of interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-β (TGF-β) in the HBeAg+ group were all significantly higher than those in the HBeAg- group (P < 0.05), but there was no significant difference in the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) between the HBeAg+ group and the HBeAg- group (P > 0.05).
CONCLUSIONS: HBeAg+ can increase the HBV-DNA levels in the PB of patients with HBV/TP co-infection, in turn triggering the body to initiate cellular immunity, increasing the levels of T lymphocyte subsets, and promote the secretion of cytokines.

This study aimed to investigatethe mechanism of stewing with tea polyphenols (TP) on the properties of boiled egg white gel (BEWG). The results indicated that, during the stewing process, soluble protein and hardness showed an overall increasing trend, while surface hydrophobicity showed a decreasing trend with blue-shift. The free sulfhydryl group showed that TP could promote the formation of disulfide bonds, and the position of immobilized water at T2 showed a decreasing trend. Environmental scanning electron microscopy and SDS-PAGE showed that the protein gel aggregation degree increased. Moreover, Fourier transform infrared spectrometry showed that protein polarity increased and that α-helices, β-turn, intramolecular β-sheets, as well as intermolecular antiparallel β-sheets showed an increasing trend. Generally, TP strengthened protein aggregation by promoting the formation of disulfide and hydrogen bonds, thus enhancing the gel strength of BEWG. Moreover, the secondary structure of proteins became more stable under the action of TP, and the higher the concentration of TP, the greater the effect on BEWG. PRACTICAL APPLICATION: TP, an ideal, cheap, and safe natural food additive, can be applied to the processing of egg products because the addition of TP can significantly improve the gel strength of egg white.

Although commonly thought to produce prostacyclin (prostaglandin I2 ; PGI2 ) that evokes vasodilatation and protects vessels from the development of diseases, the endothelial cyclooxygenase (COX)-mediated metabolism has also been found to release substance(s) called endothelium-derived contracting factor(s) (EDCF) that causes endothelium-dependent contraction and implicates in endothelial dysfunction of disease conditions. Various mechanisms have been proposed for the process; however, the major endothelial COX metabolite PGI2 , which has been classically considered to activate the I prostanoid receptor (IP) that mediates vasodilatation and opposes the effects of thromboxane (Tx) A2 produced by COX in platelets, emerges as a major EDCF in health and disease conditions. Our recent studies from genetically altered mice further suggest that vasomotor reactions to PGI2 are collectively modulated by IP, the vasoconstrictor Tx-prostanoid receptor (TP; the prototype receptor of TxA2 ) and E prostanoid receptor-3 (EP3; a vasoconstrictor receptor of PGE2 ) although with differences in potency and efficacy; a contraction to PGI2 reflects activities of TP and/or EP3 outweighing that of the concurrently activated IP. Here, we discuss the history of endothelium-dependent contraction, evidences that support the above hypothesis, proposed mechanisms for the varied reactions to endothelial PGI2 synthesis as well as the relation of its dilator activity to the effect of another NO-independent vasodilator mechanism, the endothelium-derived hyperpolarizing factor. Also, we address the possible pathological and therapeutic implications as well as questions remaining to be resolved or limitations of our above findings obtained from genetically altered mouse models.

Infectious diseases, such as HCV infection, HBV infection and syphilis, put a huge burden on public health. Accurate and fast testing is required for clinical usage.
This study aimed to evaluate the clinical performance of Elecsys® Anti-HCV II, Elecsys® HBsAg II and Elecsys® Syphilis using samples from routine diagnosis in China.
Specificity was tested in approximately 3000 unselected pseudonymized samples from routine clinical patients for each assay. Sensitivity of HCV and HBsAg assays was tested in 2 seroconversion panels, respectively.
The 3 investigational assays on cobas e 801 were showed to have excellent sensitivity and specificity which is comparable to existing assays.
They are suitable for routine clinical diagnostic use, including pre-operative assessment in China.

A high concentration of suspended solids (SS) in swine wastewater reduces the efficiency of the biological treatment process. The current study developed a short-cut combined magnetic coagulation (MC)-sequence batch membrane bioreactor (SMBR) process to treat swine wastewater. Compared with the single SMBR process, the combined process successfully achieved similarly high removal efficiencies of chemical oxygen demand (COD), total nitrogen (TN), ammonium nitrogen (NH4+-N), and total phosphorous (TP) of 96.0%, 97.6%, 99.0%, and 69.1%, respectively, at dosages of 0.5 g/L of poly aluminium chloride (PAC), 2 mg/L of polyacrylamide (PAM), and 1 g/L of magnetic seeds in Stage II, and concentrations of TN, COD, and NH4+-N in effluent can meet the discharge standards for pollutants for livestock and poultry breeding (GB18596-2001, China). The nitrogen removal loading (NRL) was increased from 0.21 to 0.28 kg/(m3·d), and the hydraulic retention time (HRT) was shortened from 5.0 days to 4.3 days. High-throughput sequencing analysis was carried out to investigate microbial community evolution, and the results showed that the relative abundance of ammonia-oxidizing bacteria (AOB) in the SMBR increased from 0.1% without pre-treatment to 1.78% with the pre-treatment of MC.

Vasomotor reactions of prostacyclin (prostaglandin I2 ; PGI2 ) can be collectively modulated by thromboxane prostanoid receptor (TP), E-prostanoid receptor-3 (EP3), and the vasodilator I prostanoid receptor (IP). This study aimed to determine the direct effect of PGI2 on renal arteries and/or the whole renal vasculature and how each of these receptors is involved. Experiments were performed on vessels or perfused kidneys of wild-type mice and/or mice with deficiency in TP (TP-/- ) and/or EP3. Here we show that PGI2 did not evoke relaxation, but instead resulted in contraction of main renal arteries (from ~0.001-0.01 µM) or reduction of flow in perfused kidneys (from ~1 µM); either of them was reversed into a dilator response in TP-/- /EP3-/- counterparts. Also, we found that in renal arteries although it has a lesser effect than TP-/- on the maximal contraction to PGI2 (10 µM), EP3-/- but not TP-/- resulted in relaxation to the prostanoid at 0.01-1 µM. Meanwhile, TP-/- only significantly reduced the contractile activity evoked by PGI2 at ≥0.1 µM. These results demonstrate that PGI2 may evoke an overall vasoconstrictor response in the mouse renal vasculature, reflecting activities of TP and EP3 outweighing that of the vasodilator IP. Also, our results suggest that EP3, on which PGI2 can have a potency similar to that on IP, plays a major role in the vasoconstrictor effect of the prostanoid of low concentrations (≤1 µM), while TP, on which PGI2 has a lower potency but higher efficacy, accounts for a larger part of its maximal contractile activity.