Effect of Salt Substitution on Cardiovascular Events and Death.

BACKGROUND: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain. METHODS: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia. RESULTS: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76). CONCLUSIONS: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).

Configurational Entropy Strategy Enhanced Structure Stability Achieves Robust Cathode for Aluminum Batteries.

Rechargeable aluminum batteries (RABs) are an emerging energy storage device owing to the vast Al resources, low cost, and high safety. However, the poor cyclability and inferior reversible capacity of cathode materials have limited the enhancement of RABs performance. Herein, a high configurational entropy strategy is presented to improve the electrochemical properties of RABs for the first time. The high-entropy (Fe, Mn, Ni, Zn, Mg)3 O4 cathode exhibits an ultra-stable cycling ability (109 mAh g-1 after 3000 cycles), high specific capacity (268 mAh g-1 at 0.5 A g-1 ), and rapid ion diffusion. Ex situ characterizations indicate that the operational mechanism of (Fe, Mn, Ni, Zn, Mg)3 O4 cathode is mainly based on the redox process of Fe, Mn, and Ni. Theoretical calculations demonstrate that the oxygen vacancies make a positive contribution to adjusting the distribution of electronic states, which is crucial for enhancing the reaction kinetics at the electrolyte and cathode interface. These findings not only propose a promising cathode material for RABs, but also provide the first elucidation of the operational mechanism and intrinsic information of high-entropy electrodes in multivalent ion batteries.

Loss-tailoring single-mode high-power supersymmetric lasers.

Diode lasers with high beam quality and high power have many promising applications. However, high beam quality is always in conflict with high power. In this Letter, we theoretically and experimentally confirm the mode instability property of supersymmetric structures at higher operating currents. Meanwhile, we propose a loss-tailoring diode laser based on a supersymmetric structure, which enables the higher-order lateral modes to obtain higher losses, raises the excitation threshold of the higher-order lateral modes, and achieves a stable fundamental-lateral-mode output at higher current operation. The device obtained a quasi-single-lobe lateral far-field distribution with the full width at half maximum (FWHM) of 7.58° at 350 mA under room temperature, which is a 65% reduction compared to the traditional Fabry-Perot (FP) diode lasers. Moreover, the M2 of 2.181@350 mA has an improvement of about 37% over traditional FP and supersymmetric structure lasers.

Exploring the Impact of Visual Heat Conduction Paths on Thermal Conductivity of Polymer Composites and the Practical Applications.

The theory of heat conduction paths has been widely recognized and widely studied in the research about the thermal conductivity of thermal conductive polymer composites at present. Encapsulating polymer pellets with thermally conductive fillers and processing them into thermally conductive polymer composites is a simple and effective method for constructing heat conduction paths. It is meaningful to investigate the related heat conduction mechanism of this method. Otherwise, this approach can significantly preserve the performance of the polymer substrate, making it highly valuable for practical material applications. In this work, polyethylene-octene elastomer (POE) pellets were encapsulated with thermal conductive fillers by physical absorption. Subsequently, the composite films containing heat conduction paths were fabricated using the encapsulated POE pellets through a heating press. Alumina (Al2O3), boron nitride (BN), and alumina/boron nitride hybrid (Al2O3/BN) fillers were used to prepare Al2O3@POE, BN@POE, and BN/Al2O3@POE composite films to investigate the influence of filler shapes on heat conduction path construction. The influence of the constitute and density of heat conduction paths on the thermal conductivity of composite films was analyzed by infrared thermal imaging, finite element analysis, and thermal resistance theory in detail. Owing to the reserved good adhesion and flexibility of the POE substrate, the composite films could be directly used as thermal interface materials for chip cooling, which presented a good heat dissipation effect. Furthermore, a series of integrated composite materials were prepared by the combination of encapsulated pellets with various functional films (copper foil, aluminum foil, and graphite sheet) through a one-pot heating press, exhibiting a good electromagnetic shielding effect. The performance of the composites and the corresponding preparation method demonstrate the strong significance of this research for practical applications.

Regioselective N-Trideuteromethylation of Tautomeric Polyaza Heterocycles.

Methods for regioselective N-trideuteromethylation of tautomeric polyaza heterocycles are highly sought-after. Disclosed herein is an N-trideuterated methylation reaction of imidazoles and pyrazoles with high regioselectivity and deuterium purity using easily available CF3SO3CD3 as the -CD3 source. This method enables the easy synthesis of important deuterium-labeled azoles, including dimetridazole-d3, ipronidazole-d3, hydroxy dimetridazole-d3, and ronidazole-d3.

Design and synthesis of novel site-specific antibody-drug conjugates that target TROP2.

The approval of Trodelvy® validates TROP2 as a druggable but challenging target for antibody-drug conjugates (ADCs) to treat metastatic triple-negative breast cancer (mTNBC). Here, based on the TROP2-targeted antibody sacituzumab, we designed and developed several site-specific ADC candidates, which employ MMAE (monomethyl auristatin E) as the toxin, via IgG glycoengineering or affinity-directed traceless conjugation. Systematic evaluation of these site-specific ADCs in homogeneity, hydrophilicity, stability, and antitumor efficiency was conducted. The results indicate that the site-specific ADCs gsADC 3b made from one-step glycoengineering exhibit good aggregation stability and in vivo efficacy, providing a new format of ADCs that target TROP2.

Abnormalities of regional spontaneous brain activity in poststroke aphasia: a meta-analysis.

Poststroke aphasia is an acquired language disorder and has been proven to have adverse effects on patients' social skills and quality of life. However, there are some inconsistencies in the neuroimaging studies investigating poststroke aphasia from the perspective of regional alterations. A meta-analysis has been employed to examine the common pattern of abnormal regional spontaneous brain activity in poststroke aphasia in the current study. Specifically, the Anisotropic effect-size version of seed-based d mapping was utilized, and 237 poststroke aphasia patients and 242 healthy controls (HCs) from 12 resting-state functional magnetic resonance imaging studies using amplitude of low-frequency fluctuations (ALFF), fractional ALFF, or regional homogeneity were included. The results showed that compared with HCs, patients with poststroke aphasia demonstrated increased regional spontaneous brain activity in the right insula, right postcentral gyrus, left cerebellar lobule IX, left angular gyrus, right caudate nucleus, left parahippocampal gyrus, and right supplementary motor area, and decreased regional spontaneous brain activity in the left cerebellar lobule VI, left median cingulate and paracingulate gyri, right cerebellar crus I, and left supplementary motor area. The study could provide further evidence for pathophysiological mechanism of poststroke aphasia and help find targets for treatment.

Light consistency correction for the liquid crystal tunable filter hyperspectral imaging system.

In hyperspectral images, every pixel encompasses continuous spectral information. Compared with traditional colorimeters, using hyperspectral imaging systems (HIS) for fabric color measurement can result in obtaining richer color information. However, measuring fabric colors with liquid crystal tunable filter HIS can lead to challenges related to light consistency. In this paper, we adopted an innovative approach, integrating gradient boosted decision trees with a sliding window algorithm to develop a uniformity calibration model addressing the illumination uniformity issue. To address the consistency issues across various light sources, we further adopted a deep neural network (DNN) model to correct the reflectance measurements under different light sources. Subsequently, this model was merged with the uniformity calibration model to form a light-consistency correction model. Through calibration, we successfully reduced the color difference of the corrected samples from 3.636 to 0.854, an enhancement of 76.51%. This means that after calibration we can achieve consistency in fabric color measurements under nonuniform lighting and different light sources.

Analysis of risky sexual behaviors among male college students who were sexually active in Sichuan, China: a cross-sectional survey.

BACKGROUND: Males have accounted for a significant share of new HIV infections among young people in the recent years. This study aimed to identify the factors associated with risky sexual behaviors, including early sexual debut, multiple sexual partnership and condomless sex, among sexually active male college students and provide implications for tailored health interventions. METHODS: The cross-sectional study was conducted from December 2020 to December 2021 in 16 colleges that were located in Sichuan Province, one of the high-risk areas in China. Overall 1640 male college students who reported sexually experienced were analyzed in this study. Multivariable logistic regression analysis was applied to determine factors associated with early sexual debut, multiple sexual partnership and condomless sex. RESULTS: The average age of included male students was 19.95 ± 1.56. Of them, 27.74% initiated sexual behavior early, 48.60% reported multiple sexual partnership, and 16.52% did not use condoms at the latest sexual intercourse. Students who were younger (age ≤ 19, AOR = 7.60, 95%CI: 4.84-11.93; age20-21, AOR = 3.26, 95%CI: 2.04-5.21) and self-identified as sexual minorities (AOR = 2.38, 95%CI: 1.69-3.36) were more likely to have early sexual debut. The odds of having multiple sexual partners were higher among those who were ethnic minorities (AOR = 1.79, 95%CI: 1.33-2.41) and accepted extramarital sex (AOR = 1.33, 95%CI: 1.03-1.71). The likelihood of engaging in condomless sex at the latest sexual intercourse was lower among those who had sufficient knowledgeable about HIV (AOR = 0.63, 95%CI: 0.44-0.89), were very confident in condom use efficacy (AOR = 0.26, 95%CI: 0.16-0.43) and confident (AOR = 0.48, 95%CI: 0.34-0.69). Early sexual debut was positively associated with multiple sexual partnership (AOR = 3.64, 95%CI: 2.82-4.71) and condomless sex at the latest intercourse (AOR = 1.53, 95%CI: 1.07-2.20), respectively. CONCLUSION: Early sexual debut, multiple sexual partnership and condomless sex were of considerable concern among male college students. Comprehensive sex education curricula were advised by developing customized information on HIV prevention, sexuality and empowering students with assertiveness and negotiation skills with regard to condom use during and before college.

Marital quality improves self- and partner-reported psychopathy among Chinese couples: A longitudinal study.

BACKGROUND: Psychopathy is closely related to many negative interpersonal outcomes in daily life, including violence. Therefore, psychopathy intervention in subclinical individuals has significant application value. OBJECTIVE: Guided by the personality-relationship transaction model and social investment theory, this study examined how marital quality affects self- and partner-rated psychopathy. We also used the actor-partner interdependence mediation model to explore the mediating effect of communication. METHODS: We examined self-reports and partner reports of psychopathy, marital quality, and communication among 260 married Chinese couples. RESULTS: The results indicated that marital quality directly influenced couples' self-rated psychopathy, with both actor and partner effects on husbands' psychopathy and actor effects on wives' psychopathy. Moreover, verbal communication had mediating effects at time 2 between marital quality at time 1 and partner-reported psychopathy at time 3. Meanwhile, the mediating effect of nonverbal communication was not significant. CONCLUSION: Our investigation of relationship effects on psychopathy revealed that the underlying mechanisms differed between self- and partner-rated psychopathy. The findings can highlight directions for exploring potential intervention strategies for subclinical psychopathy.

Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

Plant uptake of CO2 outpaces losses from permafrost and plant respiration on the Tibetan Plateau.

High-latitude and high-altitude regions contain vast stores of permafrost carbon. Climate warming may result in the release of CO2 from both the thawing of permafrost and accelerated autotrophic respiration, but it may also increase the fixation of CO2 by plants, which could relieve or even offset the CO2 losses. The Tibetan Plateau contains the largest area of alpine permafrost on Earth. However, the current status of the net CO2 balance and feedbacks to warming remain unclear, given that the region has recently experienced an atmospheric warming rate of over 0.3 °C decade-1 We examined 32 eddy covariance sites and found an unexpected net CO2 sink during 2002 to 2020 (26 of the sites yielded a net CO2 sink) that was four times the amount previously estimated. The CO2 sink peaked at an altitude of roughly 4,000 m, with the sink at lower and higher altitudes limited by a low carbon use efficiency and a cold, dry climate, respectively. The fixation of CO2 in summer is more dependent on temperature than the loss of CO2 than it is in the winter months, especially at higher altitudes. Consistently, 16 manipulative experiments and 18 model simulations showed that the fixation of CO2 by plants will outpace the loss of CO2 under a wetting-warming climate until the 2090s (178 to 318 Tg C y-1). We therefore suggest that there is a plant-dominated negative feedback to climate warming on the Tibetan Plateau.

Linc00511 Promotes Thyroid Cancer Through the miR-4739/RNF38 Pathway.

Objective: To analyze the effect of Linc00511 on thyroid cancer through the miR-4739/RNF38 pathway. Methods: A total of 78 patients in our hospital from July 2020 to July 2021 were collected, which were diagnosed with thyroid cancer after clinicopathological examination. Their cancer tissue samples were included in the thyroid cancer tissue group, and the fat 2 cm tissue samples were included in the para-cancer tissue group. Real-time quantitative PCR was used to detect the expression of Linc00511, miR-4739 and RNF38 in tissue samples from the two groups. Statistical analysis of data was performed using SPSS26.0. The correlation between Linc00511, miR-4739 and RNF38 were analyzed by Pearson's correlation coefficient. The expression of Linc00511 in thyroid cancer tissues with different clinicopathological characteristics were compared. Results: The expression levels of Linc00511 and RNF38 in thyroid cancer group were significantly higher than paracancer group, while miR-4739 levels were significantly lower (P < .05). Pearson correlation coefficient analysis showed that there was significant negative correlation between Linc00511 and miR-4739 expression and significant positive correlation between Linc00511 and RNF38 expression (P < .05). There was no significant difference in the expression of Linc00511 among different ages, sexes, and cancer types (P > .05). The expression of Linc00511 in patients with TNM stages I, II, and III were increased with the increase of TNM stage (P < .05). The expression of Linc00511 in patients with tumor diameter ≥1 cm was higher than that in patients with tumor diameter <1 cm and the difference was statistically significant (P < .05). Conclusion: Linc00511 and RNF38 were significantly overexpressed in thyroid cancer tissues, while miR-4739 was significantly underexpressed. In thyroid cancer, Linc00511 can promote the invasion and metastasis of thyroid cancer cells by targeting miR-4739 and RNF38, and its expression level may reflect the progression of thyroid cancer, which can provide target reference for the clinical treatment of thyroid cancer.

Environmental cadmium exposure perturbs systemic iron homeostasis via hemolysis and inflammation, leading to hepatic ferroptosis in common carp (Cyprinus carpio L.).

Cadmium (Cd) pollution is considered a pressing challenge to eco-environment and public health worldwide. Although it has been well-documented that Cd exhibits various adverse effects on aquatic animals, it is still largely unknown whether and how Cd at environmentally relevant concentrations affects iron metabolism. Here, we studied the effects of environmental Cd exposure (5 and 50 µg/L) on iron homeostasis and possible mechanisms in common carp. The data revealed that Cd elevated serum iron, transferrin saturation and iron deposition in livers and spleens, leading to the disruption of systemic iron homeostasis. Mechanistic investigations substantiated that Cd drove hemolysis by compromising the osmotic fragility and inducing defective morphology of erythrocytes. Cd concurrently exacerbated hepatic inflammatory responses, resulting in the activation of IL6-Stat3 signaling and subsequent hepcidin transcription. Notably, Cd elicited ferroptosis through increased iron burden and oxidative stress in livers. Taken together, our findings provide evidence and mechanistic insight that environmental Cd exposure could undermine iron homeostasis via erythrotoxicity and hepatotoxicity. Further investigation and ecological risk assessment of Cd and other pollutants on metabolism-related effects is warranted, especially under the realistic exposure scenarios.

Subsidence Characteristics in North Anhui Coal Mining Areas Using Space-Air-Ground Collaborative Observations.

To fully comprehend the patterns of land and ecological damage caused by coal mining subsidence, and to scientifically carry out ecological mine restoration and management, it is urgent to accurately grasp the information of coal mining, particularly in complex coaling areas, such as North Anhui, China. In this paper, a space-air-ground collaborative monitoring system was constructed for coal mining areas based on multi-source remote sensing data and subsidence characteristics of coaling areas were investigated in North Anhui. It was found that from 2019 to 2022, 16 new coal mining subsidence areas were found in northern Anhui, with the total area increasing by 8.1%. In terms of land use, water areas were increased by 101.9 km2 from 2012 to 2022, cultivated land was decreased by 99.3 km2, and residence land was decreased by 11.8 km2. The depth of land subsidence in the subsidence areas is divided into 307.9 km2 of light subsidence areas with a subsidence depth of less than 500 mm; 161.8 km2 of medium subsidence areas with a subsidence depth between 500 mm and 1500 mm; and 281.2 km2 of heavy subsidence areas with a subsidence depth greater than 1500 mm. The total subsidence governance area is 191.2 km2, accounting for 26.5% of the total subsidence area. From the perspective of prefecture-level cities, the governance rate reaches 51.3% in Huaibei, 10.1% in Huainan, and 13.6% in Fuyang. The total reclamation area is 68.8 km2, accounting for 34.5% of the subsidence governance area. At present, 276.1 km2 within the subsidence area has reached stable subsidence conditions, mainly distributed in the Huaibei mining area, which accounts for about 60% of the total stable subsidence area.

Insights into the complementation potential of the extreme acidophile's orthologue in replacing Escherichia coli hfq gene-particularly in bacterial resistance to environmental stress.

Acidithiobacillus caldus is a typical extreme acidophile widely used in the biohydrometallurgical industry, which often experiences extreme environmental stress in its natural habitat. Hfq, an RNA-binding protein, typically functions as a global regulator involved in various cellular physiological processes. Yet, the biological functions of Hfq derived from such extreme acidophile have not been extensively investigated. In this study, the recombinant strain Δhfq/Achfq, constructed by CRISPR/Cas9-mediated chromosome integration, fully or partially restored the phenotypic defects caused by hfq deletion in Escherichia coli, including impaired growth performance, abnormal cell morphology, impaired swarming motility, decreased stress resistance, decreased intracellular ATP and free amino acid levels, and attenuated biofilm formation. Particularly noteworthy, the intracellular ATP level and biofilm production of the recombinant strain were increased by 12.2% and 7.0%, respectively, compared to the Δhfq mutant. Transcriptomic analysis revealed that even under heterologous expression, AcHfq exerted global regulatory effects on multiple cellular processes, including metabolism, environmental signal processing, and motility. Finally, we established a potential working model to illustrate the regulatory mechanism of AcHfq in bacterial resistance to environmental stress.

Cost-Effectiveness of a Household Salt Substitution Intervention: Findings From 20 995 Participants of the Salt Substitute and Stroke Study.

BACKGROUND: SSaSS (Salt Substitute and Stroke Study), a 5-year cluster randomized controlled trial, demonstrated that replacing regular salt with a reduced-sodium, added-potassium salt substitute reduced the risks of stroke, major adverse cardiovascular events, and premature death among individuals with previous stroke or uncontrolled high blood pressure living in rural China. This study assessed the cost-effectiveness profile of the intervention. METHODS: A within-trial economic evaluation of SSaSS was conducted from the perspective of the health care system and consumers. The primary health outcome assessed was stroke. We also quantified the effect on quality-adjusted life-years (QALYs). Health care costs were identified from participant health insurance records and the literature. All costs (in Chinese yuan [¥]) and QALYs were discounted at 5% per annum. Incremental costs, stroke events averted, and QALYs gained were estimated using bivariate multilevel models. RESULTS: Mean follow-up of the 20 995 participants was 4.7 years. Over this period, replacing regular salt with salt substitute reduced the risk of stroke by 14% (rate ratio, 0.86 [95% CI, 0.77-0.96]; P=0.006), and the salt substitute group had on average 0.054 more QALYs per person. The average costs (¥1538 for the intervention group and ¥1649 for the control group) were lower in the salt substitute group (¥110 less). The intervention was dominant (better outcomes at lower cost) for prevention of stroke as well as for QALYs gained. Sensitivity analyses showed that these conclusions were robust, except when the price of salt substitute was increased to the median and highest market prices identified in China. The salt substitute intervention had a 95.0% probability of being cost-saving and a >99.9% probability of being cost-effective. CONCLUSIONS: Replacing regular salt with salt substitute was a cost-saving intervention for the prevention of stroke and improvement of quality of life among SSaSS participants.

Characteristics of vaginal microbiota in various cervical intraepithelial neoplasia: a cross-sectional study.

BACKGROUND: Precancerous lesions of cervical cancer exhibit characteristics indicative of natural progression. To prevent overtreatment of patients whose cervical intraepithelial neoplasia (CIN) in regression and to predict the onset of invasive cervical cancer at an early stage, we've identified the vaginal microbiome as a potential key factor, which is associated with both HPV infection and the various cervical intraepithelial neoplasia. This study aims to investigate the microbiome characteristics of patients with various cervical intraepithelial neoplasia. METHODS: Utilizing high-throughput 16S ribosomal RNA (16S rRNA) sequencing technology, a description of the characteristics and community composition of Vaginal Microbiota (VMB) was conducted among 692 Chinese women infected with the High-risk Human Papillomavirus (HR-HPV). RESULTS: As the grade of the lesions increased, the proportions of Lactobacillus and Pseudomonas demonstrated a significant declining trend, while the proportions of Gardnerella, Dialister, and Prevotella significantly increased. The diversity of the VMB was more significant in high-grade CIN. Furthermore, KEGG pathway enrichment analysis indicates that high-grade cervical intraepithelial neoplasia can inhibit various pathways, including those of phosphotransferase system, transcription factors, Fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism, which may contribute to the development of early cervical cancer symptoms. CONCLUSION: Patients with CIN exhibit a distinct vaginal microbial profile characterized by a decrease in Lactobacillus and Pseudomonas, and an increase in Gardnerella, Prevotella, and Dialister. The proliferation and diminution of these two types of microbial communities are interrelated, suggesting a mutual restraint and balance among them. Disruption of this regulatory balance could potentially lead to the onset of cervical lesions and carcinogenesis. Retrospectively registered: This study was approved by the Ethics Committee of the Beijing Chaoyang Hospital affiliated with the Capital Medical University (NO.2023-S-415).

One-Pot Assembly of Dual-Site-Specific Antibody-Drug Conjugates via Glycan Remodeling and Affinity-Directed Traceless Conjugation.

The drug-to-antibody ratio (DAR) value and dual-drug combination greatly influence the therapeutic index of antibody-drug conjugates (ADCs). The reported approaches usually require multifunctional branched linkers, a combination of complicated technologies, or protein-protein ligation, which may incorporate multihydrophobic fragments or result in low coupling efficiency. Herein, we developed a facile and efficient one-pot method to assemble dual-site-specific ADCs with defined DARs at both the N-glycosylation site and K248 site, either with the same payloads or with two types of payloads. The constructed dual-site ADCs showed acceptable homogeneity, excellent buffer stability, and enhanced in vitro and in vivo efficiency.

Dietary Bacillus velezensis R-71003 and sodium gluconate improve antioxidant capacity, immune response and resistance against Aeromonas hydrophila in common carp.

This study aimed to evaluate the effects of dietary supplementation with Bacillus velezensis R-71003 combined with sodium gluconate on antioxidant capacity, immune response and resistance against Aeromonas hydrophila in common carp. In addition, the biocontrol potential of the secondary metabolites of B. velezensis R-71003 was also evaluated to analyze the possible mechanism of B. velezensis R-71003 against A. hydrophila. The results indicated that the antibacterial crude extract of B. velezensis R-71003 can destroy the cell wall of A. hydrophila. Moreover, the results showed that dietary B. velezensis R-71003 could promote antioxidant capacity, which significantly increased the activities of CAT and SOD and decreased the content of MDA. Additionally, B. velezensis R-71003 supplementation significantly enhanced the immunity of common carp, as measured by the mRNA expression levels of cytokine-related genes (TNF-α, TGF-ß, IL-1ß and IL-10). In addition, dietary B. velezensis R-71003 exhibited an upregulation of IL-10 and a downregulation of IL-1ß, coupled with higher survival rates when challenged with A. hydrophila compared to the positive group. Furthermore, compared to prechallenge, the mRNA expression levels of TLR-4, MyD88, IRAK1, TRAF6, TRIF and NF-κB in the head kidney of common carp were significantly increased after challenge. The fish fed the B. velezensis R-71003 diet showed lower expression of TLR-4, MyD88, IRAK1, TRAF6, TRIF and NF-κB after the challenge than those fed the control diet. Thus, this study revealed that B. velezensis R-71003 can improve the resistance of common carp to pathogenic bacteria by destroying bacterial cell walls and improving fish immunity by activating the TLR4 signaling pathway. Importantly, this study indicated that sodium gluconate has a positive effect on B. velezensis R-71003 in enhancing the anti-infection ability of common carp. The results of this study will lay the foundation for the application of B. velezensis R-71003 in combination with sodium gluconate as an alternative to antibiotics in aquaculture.