Crowdsourced partner services among men who have sex with men living with HIV: A pilot randomized controlled trial in China.

BACKGROUND: This study aimed to assess the acceptability, feasibility, and preliminary effectiveness of a crowdsourced HIV partner services (PS) intervention among men who have sex with men living with HIV (MLWH) in China. METHODS: A pilot two-arm randomized controlled trial (RCT) was conducted in three HIV testing clinics in China. The control arm received conventional HIV PS while the intervention arm received a crowdsourced intervention, including HIV self-testing kits for secondary distribution (HIVST-SD), digital education materials, and assisted PS. The intervention was developed through two-phase crowdsourcing events including an open call and a Designathon. The primary outcomes were measured by the 3-month follow-up rate (i.e., the proportion of participants who completed the follow-up survey to report HIV PS outcomes three months after enrollment) and the frequency of using intervention components (feasibility), index evaluation of intervention components (acceptability), and the proportion of partners getting HIV testing (preliminary effectiveness). RESULTS: The study enrolled 121 newly diagnosed MLWH between July 2021 and May 2022. The 3-month follow-up rates were 93% (75/81) and 83% (33/40) in the intervention and control arms, respectively. Crowdsourced intervention components demonstrated feasibility, with all indexes utilizing digital educational materials, 23 successfully using HIVST-SD, and six employing provider-referral to notify nine sexual partners. Acceptability was high, with HIVST-SD and digital educational materials rated 4·4 and 4.1 out of 5. The proportion of partners receiving HIV testing was 11% higher in the intervention arm than in the control arm (marginal significance with 95% CI = [-2%, 24%], 38% vs. 27%). CONCLUSION: The crowdsourced HIV PS intervention was acceptable and feasible, suggesting the potential to facilitate partner HIV testing among Chinese MLWH. Further implementation research is recommended to expand HIV PS among key populations in low- and middle-income countries.Clinical trial registration ID: NCT04971967 (Protocol ID: 19-0496).

Comparative characteristics of early-onset vs. late-onset advanced colorectal cancer: a nationwide study in China.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC, diagnosed in patients under the age of 50 years) has been increasing around the world. Here, we aimed to systematically identify distinctive features of EOCRC. METHODS: From 2020 to 2021, we conducted a nationwide survey in 19 hospitals, collecting data on advanced CRC patients' demographics, clinical features, disease knowledge, medical experiences, expenditures, and health-related quality of life (HRQOL). We compared these features between EOCRC and late-onset colorectal cancer (LOCRC, ≥ 50 years old) groups and analyzed the association between EOCRC and HRQOL using multivariate linear regression. FINDINGS: In total, 991 patients with EOCRC and 3581 patients with LOCRC were included. Compared to the LOCRC group, the EOCRC group had higher levels of education, were more informed about the risk factors for CRC, were more likely to have widespread metastases throughout the body, were more inclined to undergo gene testing, and were more likely to opt for targeted therapy, radiotherapy, and chemotherapy. However, HRQOL in the EOCRC group was similar to that of the LOCRC group, and no significant association was observed between EOCRC and HRQOL (beta: -0.753, P value: 0.307). INTERPRETATION: In Chinese patients, EOCRC patients had more aggressive features. Despite undergoing more intensified treatments and gene testing, they had similar HRQOL compared with LOCRC. These findings advocate for a more tailored approach to treatment, especially for young CRC patients with advanced TNM stages and metastasis.

Genome-wide identification of the key kinesin genes during fiber and boll development in upland cotton (Gossypium hirsutum L.).

Kinesin is a kind of motor protein, which interacts with microtubule filaments and regulates cellulose synthesis. Cotton fiber is a natural model for studying the cellular development and cellulose synthesis. Therefore, a systematic research of kinesin gene family in cotton (Gossypium spp.) will be beneficial for both understanding the function of kinesin protein and assisting the fiber improvement. Here, we aimed to identify the key kinesin genes present in cotton by combining genome-wide expression profile data, association mapping, and public quantitative trait loci (QTLs) in upland cotton (G. hirsutum L.). Results showed that 159 kinesin genes, including 15 genes of the kinesin-13 gene subfamily, were identified in upland cotton; of which 157 kinesin genes can be traced back to the diploid ancestors, G. raimondii and G. arboreum. Using a combined analysis of public QTLs and genome-wide expression profile information, there were 29 QTLs co-localized together with 28 kinesin genes in upland cotton, including 10 kinesin-13 subfamily genes. Genome-wide expression profile data indicated that, among the 28 co-localized genes, seven kinesin genes were predominantly expressed in fibers or ovules. By association mapping analysis, 30 kinesin genes were significantly associated with three fiber traits, among which a kinesin-13 gene, Ghir_A11G028430, was found to be associated with both cotton boll length and lint weight, and one kinesin-7 gene, Ghir_D04G017880 (Gh_Kinesin7), was significantly associated with fiber strength. In addition, two missense mutations were identified in the motor domain of the Gh_Kinesin7 protein. Overall, the kinesin gene family seemingly plays an important role in cotton fiber and boll development. The exploited kinesin genes will be beneficial for the genetic improvement of fiber quality and yield.

Interfacial "Double-Terminal Binding Sites" Catalysts Synergistically Boosting the Electrocatalytic Li2S Redox for Durable Lithium-Sulfur Batteries.

Catalytic conversion of polysulfides emerges as a promising approach to improve the kinetics and mitigate polysulfide shuttling in lithium-sulfur (Li-S) batteries, especially under conditions of high sulfur loading and lean electrolyte. Herein, we present a separator architecture that incorporates double-terminal binding (DTB) sites within a nitrogen-doped carbon framework, consisting of polar Co0.85Se and Co clusters (Co/Co0.85Se@NC), to enhance the durability of Li-S batteries. The uniformly dispersed clusters of polar Co0.85Se and Co offer abundant active sites for lithium polysulfides (LiPSs), enabling efficient LiPS conversion while also serving as anchors through a combination of chemical interactions. Density functional theory calculations, along with in situ Raman and X-ray diffraction characterizations, reveal that the DTB effect strengthens the binding energy to polysulfides and lowers the energy barriers of polysulfide redox reactions. Li-S batteries utilizing the Co/Co0.85Se@NC-modified separator demonstrate exceptional cycling stability (0.042% per cycle over 1000 cycles at 2 C) and rate capability (849 mAh g-1 at 3 C), as well as deliver an impressive areal capacity of 10.0 mAh cm-2 even in challenging conditions with a high sulfur loading (10.7 mg cm-2) and lean electrolyte environments (5.8 µL mg-1). The DTB site strategy offers valuable insights into the development of high-performance Li-S batteries.

Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

Fundamentally Manipulating the Electronic Structure of Polar Bifunctional Catalysts for Lithium-Sulfur Batteries: Heterojunction Design versus Doping Engineering.

Heterogeneous structures and doping strategies have been intensively used to manipulate the catalytic conversion of polysulfides to enhance reaction kinetics and suppress the shuttle effect in lithium-sulfur (Li-S) batteries. However, understanding how to select suitable strategies for engineering the electronic structure of polar catalysts is lacking. Here, a comparative investigation between heterogeneous structures and doping strategies is conducted to assess their impact on the modulation of the electronic structures and their effectiveness in catalyzing the conversion of polysulfides. These findings reveal that Co0.125 Zn0.875 Se, with metal-cation dopants, exhibits superior performance compared to CoSe2 /ZnSe heterogeneous structures. The incorporation of low Co2+ dopants induces the subtle lattice strain in Co0.125 Zn0.875 Se, resulting in the increased exposure of active sites. As a result, Co0.125 Zn0.875 Se demonstrates enhanced electron accumulation on surface Se sites, improved charge carrier mobility, and optimized both p-band and d-band centers. The Li-S cells employing Co0.125 Zn0.875 Se catalyst demonstrate significantly improved capacity (1261.3 mAh g-1 at 0.5 C) and cycle stability (0.048% capacity delay rate within 1000 cycles at 2 C). This study provides valuable guidance for the modulation of the electronic structure of typical polar catalysts, serving as a design directive to tailor the catalytic activity of advanced Li-S catalysts.

Influence of Crosslink Density on Electrical Performance and Rheological Properties of Crosslinked Polyethylene.

To investigate the influence of the crosslinked polyethylene (XLPE) structure on electrical performance, various analytical methods were employed to study polyethylene structures with different degrees of crosslinking. Dynamic rheological analysis was conducted to determine material shear viscosity, dynamic viscosity, storage modulus (G'), loss modulus (G″), and other rheological parameters. Additionally, the electrical performance of the material was analyzed by studying the phenomenon of space charge accumulation under direct current voltage. The results indicate that with an increasing mass fraction of the crosslinking agent, the crosslink density of crosslinked polyethylene initially increases and then decreases. When the dicumyl peroxide (DCP) content exceeds 1.0 wt.%, there is an accumulation of like-polarity space charges. The best rheological processing performance of crosslinked polyethylene is observed when the DCP content is in the range of 1.0-1.5 wt.%.

Evaluation of the psychometrics of the Social Impact Scale and its association with depression among asymptomatic COVID-19 carriers.

BACKGROUND: COVID-19 carriers experience psychological stresses and mental health issues such as varying degrees of stigma. The Social Impact Scale (SIS) can be used to measure the stigmatisation of COVID-19 carriers who experience such problems. AIMS: To evaluate the reliability and validity of the Chinese version of the SIS, and the association between stigma and depression among asymptomatic COVID-19 carriers in Shanghai, China. METHOD: A total of 1283 asymptomatic COVID-19 carriers from Shanghai Ruijin Jiahe Fangcang Shelter Hospital were recruited, with a mean age of 39.64 ± 11.14 years (59.6% male). Participants completed questionnaires, including baseline information and psychological measurements, the SIS and Self-Rating Depression Scale. The psychometrics of the SIS and its association with depression were examined through exploratory factor analysis, confirmatory factor analysis and receiver operating characteristic analysis. RESULTS: The average participant SIS score was 42.66 ± 14.61 (range: 24-96) years. Analyses suggested the model had four factors: social rejection, financial insecurity, internalised shame and social isolation. The model fit statistics of the four-factor SIS were 0.913 for the comparative fit index, 0.902 for the Tucker-Lewis index and 0.088 for root-mean-square error of approximation. Standard estimated factor loadings ranged from 0.509 to 0.836. After controlling for demographic characteristics, the total score of the 23-item SIS predicted depression (odds ratio: 1.087, 95% CI 1.061-1.115; area under the curve: 0.84, 95% CI 0.788-0.892). CONCLUSIONS: The Chinese version of the SIS showed good psychometric properties and can be used to assess the level of perceived stigma experienced by asymptomatic COVID-19 carriers.

ω-transaminase-catalyzed synthesis of (R)-2-(1-aminoethyl)-4-fluorophenol, a chiral intermediate of novel anti-tumor drugs.

The chiral amine (R)-2-(1-aminoethyl)-4-fluorophenol has attracted increasing attentions in recent years in the field of pharmaceuticals because of its important use as a building block in the synthesis of novel anti-tumor drugs targeting tropomyosin receptor kinases. In the present study, a ω-transaminase (ωTA) library consisting of 21 (R)-enantioselective enzymes was constructed and screened for the asymmetric biosynthesis of (R)-2-(1-aminoethyl)-4-fluorophenol from its prochiral ketone. Using (R)-α-methylbenzylamine, D-alanine, or isopropylamine as amino donor, 18 ωTAs were identified with target activity and the enzyme AbTA, which was originally identified from Arthrobacter sp. KNK168, was found to be a potent candidate. The E. coli whole cells expressing AbTA could be used as catalysts. The optimal temperature and pH for the activity were 35-40 °C and pH8.0, respectively. Simple alcohols (such as ethanol, isopropanol, and methanol) and dimethyl sulfoxide were shown to be good cosolvents. High activities were detected when using ethanol and dimethyl sulfoxide at the concentrations of 5-20%. In the scaled-up reaction of 1-liter containing 13 mM ketone substrate, about 50% conversion was achieved in 24 h. 6.4 mM (R)-2-(1-aminoethyl)-4-fluorophenol was generated. After a simple and efficient process of product isolation and purification (with 98.8% recovery), 0.986 g yellowish powder of the product (R)-2-(1-aminoethyl)-4-fluorophenol with high (R)-enantiopurity (up to 100% enantiomeric excess) was obtained. This study established an overall process for the biosynthesis of the high value pharmaceutical chiral amine (R)-2-(1-aminoethyl)-4-fluorophenol by ωTA. Its applicable potential was exemplified by gram-scale production.

Risk-based lung cancer screening in heavy smokers: a benefit-harm and cost-effectiveness modeling study.

BACKGROUND: Annual screening through low-dose computed tomography (LDCT) is recommended for heavy smokers. However, it is questionable whether all individuals require annual screening given the potential harms of LDCT screening. This study examines the benefit-harm and cost-effectiveness of risk-based screening in heavy smokers and determines the optimal risk threshold for screening and risk-stratified screening intervals. METHODS: We conducted a comparative cost-effectiveness analysis in China, using a cohort-based Markov model which simulated a lung cancer screening cohort of 19,146 heavy smokers aged 50 ~ 74 years old, who had a smoking history of at least 30 pack-years and were either current smokers or had quit for < 15 years. A total of 34 risk-based screening strategies, varying by different risk groups for screening eligibility and screening intervals (1-year, 2-year, 3-year, one-off, non-screening), were evaluated and were compared with annual screening for all heavy smokers (the status quo strategy). The analysis was undertaken from the health service perspective with a 30-year time horizon. The willingness-to-pay (WTP) threshold was adopted as three times the gross domestic product (GDP) of China in 2021 (CNY 242,928) per quality-adjusted life year (QALY) gained. RESULTS: Compared with the status quo strategy, nine risk-based screening strategies were found to be cost-effective, with two of them even resulting in cost-saving. The most cost-effective strategy was the risk-based approach of annual screening for individuals with a 5-year risk threshold of ≥ 1.70%, biennial screening for individuals with a 5-year risk threshold of 1.03 ~ 1.69%, and triennial screening for individuals with a 5-year risk threshold of < 1.03%. This strategy had the highest incremental net monetary benefit (iNMB) of CNY 1032. All risk-based screening strategies were more efficient than the status quo strategy, requiring 129 ~ 656 fewer screenings per lung cancer death avoided, and 0.5 ~ 28 fewer screenings per life-year gained. The cost-effectiveness of risk-based screening was further improved when individual adherence to screening improved and individuals quit smoking after being screened. CONCLUSIONS: Risk-based screening strategies are more efficient in reducing lung cancer deaths and gaining life years compared to the status quo strategy. Risk-stratified screening intervals can potentially balance long-term benefit-harm trade-offs and improve the cost-effectiveness of lung cancer screenings.

Genome-wide identification of the key Kinesin genes during fiber and boll development in upland cotton (Gossypium hirsutum L).

Kinesin is a kind of motor protein, which interacts with microtubule filaments and regulates cellulose synthesis. Cotton fiber is a natural model for studying the cellular development and cellulose synthesis. Therefore, a systematic research of Kinesin gene family in cotton (Gossypium spp.) will be beneficial for both understanding the function of Kinesin protein and assisting the fiber improvement. Here, we aimed to identify the key Kinesin genes present in cotton by combining genome-wide expression profile data, association mapping, and public quantitative trait loci (QTLs) in upland cotton (Gossypium hirsutum L.). Results showed that 159 Kinesin genes, including 15 genes of the Kinesin-13 gene subfamily, were identified in upland cotton; of which 157 Kinesin genes can be traced back to the diploid ancestors, G. raimondii and G. arboreum. Using a combined analysis of public QTLs and genome-wide expression profile information, there were 29 QTLs co-localized together with 28 Kinesin genes in upland cotton, including 10 Kinesin-13 subfamily genes. Genome-wide expression profile data indicated that, among the 28 co-localized genes, seven Kinesin genes were predominantly expressed in fibers or ovules. By association mapping analysis, 30 Kinesin genes were significantly associated with three fiber traits, among which a Kinesin-13 gene, Ghir_A11G028430, was found to be associated with both cotton boll length and lint weight, and one Kinesin-7 gene, Ghir_D04G017880 (Gh_Kinesin7), was significantly associated with fiber strength. In addition, two missense mutations were identified in the motor domain of the Gh_Kinesin7 protein. Overall, the Kinesin gene family seemingly plays an important role in cotton fiber and boll development. The exploited Kinesin genes will be beneficial for the genetic improvement of fiber quality and yield.

Trimethylamine-N-oxide (TMAO) and basic fibroblast growth factor (bFGF) are possibly involved in corticosteroid resistance in adult patients with immune thrombocytopenia.

PURPOSE: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by accelerated platelet clearance. Gut dysbiosis was associated with its pathogenesis, but the underlying mechanisms have not been fully elucidated. Patients with ITP exhibit varying degrees of responsiveness to corticosteroid treatment. Therefore, prognostic indexes for corticosteroid responsiveness in ITP could offer valuable guidance for clinical practices. METHODS: The present study examined the signature of six types of gut-microbiota metabolites and forty-eight types of cytokines, chemokines, and growth factors and their clinical significance in patients with ITP. RESULTS: Both patients with good and poor corticosteroid responsiveness exhibited significantly elevated/suppressed secretion of twenty-two cyto(chemo)kins/growth factors in comparison to healthy controls. Additionally, patients with ITP demonstrated a significant decrease in plasma levels of trimethylamine-N-oxide (TMAO), which was found to be negatively correlated to circulating platelet counts, and positively correlated with Interleukin (IL)-1ß and IL-18. Notably, patients who exhibited poor response to corticosteroid treatment displayed elevated levels of TMAO and basic fibroblast growth factor (bFGF) in comparison to responders. Additionally, we found that the amalgamation of TMAO, bFGF and interleukin (IL)-13 could serve as a valuable prognostic tool for predicting CS responsiveness. CONCLUSION: Patients with ITP were characterized overall by an imbalanced secretion of cyto(cheo)kins/growth factors and inadequate levels of TMAO. The varying degrees of responsiveness to corticosteroid treatment can be attributed to different profiles of basic FGF and TMAO that might be related to overburdened oxidative stress and inflammasome overactivation, and ultimately mediate corticosteroid resistance.

Shoot-to-root communication via GmUVR8-GmSTF3 photosignaling and flavonoid biosynthesis fine-tunes soybean nodulation under UV-B light.

Legume nodulation requires light perception by plant shoots and precise long-distance communication between shoot and root. Recent studies have revealed that TGACG-motif binding factors (GmSTFs) integrate light signals to promote root nodulation; however, the regulatory mechanisms underlying nodule formation in changing light conditions remain elusive. Here, we applied genetic engineering, metabolite measurement, and transcriptional analysis to study soybean (Glycine max) nodules. We clarify a fine-tuning mechanism in response to ultraviolet B (UV-B) irradiation and rhizobia infection, involving GmUVR8-dependent UV-B perception and GmSTF3/4-GmMYB12-GmCHS-mediated (iso)flavonoid biosynthesis for soybean nodule formation. GmUVR8 receptor-perceived UV-B signal triggered R2R3-MYB transcription factors GmMYB12-dependent flavonoid biosynthesis separately in shoot and root. In shoot, UV-B-triggered flavonoid biosynthesis relied on GmUVR8a, b, c receptor-dependent activation of GmMYB12L-GmCHS8 (chalcone synthase) module. In root, UV-B signaling distinctly promotes the accumulation of the isoflavones, daidzein, and its derivative coumestrol, via GmMYB12B2-GmCHS9 module, resulting in hypernodulation. The mobile transcription factors, GmSTF3/4, bind to cis-regulatory elements in the GmMYB12L, GmMYB12B2, and GmCHS9 promoters, to coordinate UV-B light perception in shoot and (iso)flavonoid biosynthesis in root. Our findings establish a novel shoot-to-root communication module involved in soybean nodulation and reveal an adaptive strategy employed by soybean roots in response to UV-B light.

Hepatitis C Knowledge and Self-Reported Testing Behavior in the General Population in China: Online Cross-Sectional Survey.

BACKGROUND: The World Health Organization has proposed a worldwide target of eliminating hepatitis C virus (HCV) by 2030. A better understanding of HCV, testing behaviors, and associated factors in the general population is essential. OBJECTIVE: This study aimed to assess HCV knowledge, self-reported HCV testing behavior, and willingness to undergo HCV screening in the general Chinese population. METHODS: A cross-sectional online survey of the general Chinese population aged ≥15 years was conducted from November 2021 to May 2023. Participant characteristics were assessed based on their knowledge level and uptake of HCV testing. Participants ever having heard of HCV were recognized as being aware of HCV and asked additional HCV knowledge questions using a brief, validated 9-item scale. Participants with 0-3 points and who were unaware of HCV were categorized as having poor knowledge, and those with 4-6 points and 7 points were categorized as having fair and good knowledge, respectively. Participant uptake of HCV testing, testing results, reasons for undergoing or not undergoing HCV testing, and willingness to undergo HCV screening were collected through self-reports. Ordinal and binary logistic regression analyses were used to assess factors associated with the HCV knowledge level and the uptake of HCV testing, respectively. RESULTS: A total of 1491 valid participants' questionnaires were included. Of these, 714 (47.6%) participants were aware of HCV. The proportion of participants with poor, fair, and good HCV knowledge was 63.4% (945/1491), 9.3% (139/1491), and 27.3% (407/1491), respectively. A total of 465 (31.2%) participants reported ever undergoing HCV testing, and 4 (0.9%) were anti-HCV antibody positive. Most participants were tested for HCV following blood donation (353/465, 75.9%). The most common reasons for not undergoing HCV screening were a lack of HCV awareness (665/1026, 64.8%), followed by a low self-perceived risk of infection (176/1026, 17.2%). Of 1026 participants who had never undergone HCV testing, 937 (91.3%) were willing to undergo HCV screening if universal screening was provided at no cost. The HCV knowledge level was positively associated with the HCV testing rate. Participants who were less educated, lived in rural areas, resided in West China, and were currently alcohol drinkers had lower HCV knowledge and reduced odds of having undergone HCV testing. In contrast, participants with a blood donation history and a family history of hepatitis B virus or HCV infection had higher HCV knowledge and increased odds of prior testing. Participants aged ≥60 years had lower knowledge, and women had reduced odds of having undergone previous HCV testing. CONCLUSIONS: The general population of China has low HCV knowledge and testing rate. There is an urgent need for enhanced HCV awareness and scaled-up HCV screening and treatment. Individuals who are less well educated, reside in less-developed areas, currently drink alcohol, and are female should be prioritized for health education and interventions.

Self-Assembly of Palmitic Acid in the Presence of Choline Hydroxide.

To disperse fatty acids in aqueous solution, choline, a quaternary ammonium ion, has been used recently. So far, only the self-assembly of myristic acid (MA) in the presence of choline hydroxide as a function of the molar ratio has been investigated, and, thus, the current understanding of these fatty acid systems is still limited. We investigated the self-assembly of palmitic acid (PA) in the presence of choline hydroxide (ChOH) as a function of the molar ratio (R) between ChOH and PA. The self-assemblies were characterized by phase contrast microscopy, cryo-TEM, small-angle X-ray scattering, and 2H NMR. The ionization state of PA was determined by pH, conductivity, and FT-IR measurements. With increase in R, various self-assembled structures, including vesicles, lamellar phase, rigid membranes (large sheets, tubules, cones, and polyhedrals), and micelles, form in the PA/ChOH system, different from those of the MA/ChOH system. The change in R induces pH variation and, consequently, a change in the PA ionization state, which, in turn, regulates the molecular interactions, including hydrogen bonding and electrostatic interaction, leading to various self-assemblies. Temperature is an important factor used to tune the self-assembly transitions. The fatty acid choline systems studied here potentially may be applicable in medicine, chemical engineering, and biotechnology.

A Delta-Omicron Bivalent Subunit Vaccine Elicited Antibody Responses in Mice against Both Ancestral and Variant Strains of SARS-CoV-2.

Continued mutation of the SARS-CoV-2 genome has led to multiple waves of COVID-19 infections, and new variants have continued to emerge and dominate. The emergence of Omicron and its subvariants has substantially increased the infectivity of SARS-CoV-2. RBD genes of the wild-type SARS-CoV-2 strain and the Delta, Omicron BA.1 and Omicron BA.2 variants were used to construct plasmids and express the proteins in glycoengineered Pichia pastoris. A stable 4 L-scale yeast fermentation and purification process was established to obtain high-purity RBD proteins with a complex glycoform N-glycosyl structure that was fucose-free. The RBD glycoproteins were combined with two adjuvants, Al(OH)3 and CpG, which mitigated the typical disadvantage of low immunogenicity associated with recombinant subunit vaccines. To improve the broad-spectrum antiviral activity of the candidate vaccine, Delta RBD proteins were mixed with BA.2 RBD proteins at a ratio of 1:1 and then combined with two adjuvants-Al(OH)3 and CpG-to prepare a bivalent vaccine. The bivalent vaccine effectively induced mice to produce pseudovirus-neutralizing antibodies against SARS-CoV-2 variants, Delta, Beta, and Omicron sublineages BA.1, BA.2, BA.5. The bivalent vaccine could neutralize the authentic wild-type SARS-CoV-2 strain, Delta, BA.1.1, BA.2.2, BA2.3, and BA.2.12.1 viruses, providing a new approach for improving population immunity and delivering broad-spectrum protection under the current epidemic conditions.

Fish oil supplementation modifies the genetic potential for blood lipids.

Background: Dyslipidemia is a well-known risk factor for cardiovascular disease, which has been the leading cause of mortality worldwide. Although habitual intake of fish oil has been implicated in offering cardioprotective effects through triglyceride reduction, the interactions of fish oil with the genetic predisposition to dysregulated lipids remain elusive. Objectives: We examined whether fish oil supplementation can modify the genetic potential for the circulating levels of four lipids, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Methods: A total of 441,985 participants with complete genetic and phenotypic data from the UK Biobank were included in our study. Polygenic scores (PGS) were calculated in participants of diverse ancestries. Multivariable linear regression models were used to assess associations with adjustment for relevant risk factors. Results: Fish oil supplementation mitigated genetic susceptibility to elevated levels of total cholesterol, LDL-C, and triglycerides, while amplifying genetic potential for increased HDL-C among 424,090 participants of European ancestry Pinteraction<0.05. Consistent significant findings were obtained using PGS calculated based on multiple genome-wide association studies or alternative PGS methods. We also showed that fish oil significantly attenuated genetic predisposition to high triglycerides in African-ancestry participants. Conclusions: Fish oil supplementation attenuated the genetic susceptibility to elevated blood levels of total cholesterol, LDL-C, and triglycerides, while accentuating genetic potential for higher HDL-C. These results suggest that fish oil may have a beneficial impact on modifying genome-wide genetic effects on elevated lipid levels in the general population.

Shared genetic basis informs the roles of polyunsaturated fatty acids in brain disorders.

The neural tissue is rich in polyunsaturated fatty acids (PUFAs), components that are indispensable for the proper functioning of neurons, such as neurotransmission. PUFA nutritional deficiency and imbalance have been linked to a variety of chronic brain disorders, including major depressive disorder (MDD), anxiety, and anorexia. However, the effects of PUFAs on brain disorders remain inconclusive, and the extent of their shared genetic determinants is largely unknown. Here, we used genome-wide association summary statistics to systematically examine the shared genetic basis between six phenotypes of circulating PUFAs (N = 114,999) and 20 brain disorders (N = 9,725-762,917), infer their potential causal relationships, identify colocalized regions, and pinpoint shared genetic variants. Genetic correlation and polygenic overlap analyses revealed a widespread shared genetic basis for 77 trait pairs between six PUFA phenotypes and 16 brain disorders. Two-sample Mendelian randomization analysis indicated potential causal relationships for 16 pairs of PUFAs and brain disorders, including alcohol consumption, bipolar disorder (BIP), and MDD. Colocalization analysis identified 40 shared loci (13 unique) among six PUFAs and ten brain disorders. Twenty-two unique variants were statistically inferred as candidate shared causal variants, including rs1260326 (GCKR), rs174564 (FADS2) and rs4818766 (ADARB1). These findings reveal a widespread shared genetic basis between PUFAs and brain disorders, pinpoint specific shared variants, and provide support for the potential effects of PUFAs on certain brain disorders, especially MDD, BIP, and alcohol consumption.

Factors associated with afebrile presentation and delayed defervescence of bacterial meningitis in children under 3 years of age: a multi-centre retrospective analysis.

BACKGROUND: This multi-center study aimed to identify factors affecting fever and delayed defervescence in bacterial meningitis (BM) patients under 3 years of age because of the variability of fever in this patient population. METHODS: Only BM patients under 3 years treated at 49 centers in China from November 2018 to end-April 2021 were included in the study. Univariate and multivariate logistic regression analyses were performed to determine factors associated with afebrile presentation and fever of delayed defervescence. RESULTS: A total of 863 BM patients under 3 years were included in the study. Coagulase negative staphylococcus was associated with afebrile presentation (OR = 1.176), while septicaemia and ear-nose-throat infections were associated with fever (P < 0.05). The patients with fever were assigned into early and delayed defervescence groups based on defervescence time (less than and more than or equal to one week). Furthermore, Streptococcus agalactiae meningitis (OR = 1.124), concomitant gastrointestinal infection (OR = 1.276), encephalomalacia (or = 1.339), and subdural effusion (OR = 1.454) were independently associated with delayed defervescence (all P < 0.05). CONCLUSIONS: The findings can aid in the efficient utilization of fever in auxiliary diagnosis and evaluating the condition of the disease.