Metabolic obesity phenotypes and all-cause mortality among the Chinese oldest-old population: a prospective cohort study.

BACKGROUND: The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population. METHODS: This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models. RESULTS: During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11). CONCLUSIONS: MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults.

Serum 25-hydroxyvitamin D concentrations and colorectal cancer incidence in adults with type 2 diabetes.

BACKGROUND: To examine the association of serum 25-hydroxyvitamin D (25[OH]D) with colorectal cancer (CRC) risk in adults with type 2 diabetes (T2D). METHODS: Using UK Biobank data, this study included 18,453 adults with T2D. Serum 25(OH)D concentrations were determined by the chemiluminescent immunoassay method. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC outcomes. RESULTS: During a median follow-up of 8.8 years, there were 284 incident CRC cases. Compared with adults with serum 25(OH)D concentrations <25.0 nmol/L, the adjusted HRs (95% CIs) for lower to higher serum 25(OH)D concentrations (25.0 to <50.0, 50.0 to <75.0, and ≥75.0 nmol/L) were 0.61 (0.46-0.82), 0.50 (0.34-0.74), and 0.53 (0.30-0.94), respectively (Ptrend = 0.001). The risk of CRC decreased by 19.0% for per 1-SD increment in serum 25(OH)D concentrations. A nonlinear association of serum 25(OH)D concentrations with CRC risk was observed using a restricted cubic spline analysis (P nonlinearity = 0.002). CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly and nonlinearly associated with a lower risk of CRC. These findings highlight the potential benefits of maintaining adequate vitamin D levels in CRC prevention among adults with T2D.

Neutralizing antibody levels associated with injectable and aerosolized Ad5-nCoV boosters and BA.2 infection.

BACKGROUND: Several COVID-19 vaccines are in widespread use in China. Few data exist on comparative immunogenicity of different COVID-19 vaccines given as booster doses. We aimed to assess neutralizing antibody levels raised by injectable and inhaled aerosolized recombinant adenovirus type 5 (Ad5)-vectored COVID-19 vaccine as a heterologous booster after an inactivated COVID-19 vaccine two-dose primary series. METHODS: Using an open-label prospective cohort design, we recruited 136 individuals who had received inactivated vaccine primary series followed by either injectable or inhaled Ad5-vectored vaccine and measured neutralizing antibody titers against ancestral SARS-CoV-2 virus and Omicron BA.1 and BA.5 variants. We also measured neutralizing antibody levels in convalescent sera from 39 patients who recovered from Omicron BA.2 infection. RESULTS: Six months after primary series vaccination, neutralizing immunity against ancestral SARS-CoV-2 was low and neutralizing immunity against Omicron (B.1.1.529) was lower. Boosting with Ad5-vectored vaccines induced a high immune response against ancestral SARS-CoV-2. Neutralizing responses against Omicron BA.5 were ≥ 80% lower than against ancestral SARS-CoV-2 in sera from prime-boost subjects and in convalescent sera from survivors of Omicron BA.2 infection. Inhaled aerosolized Ad5-vectored vaccine was associated with greater neutralizing titers than injectable Ad5-vectored vaccine against ancestral and Omicron SARS-CoV-2 variants. CONCLUSIONS: These findings support the current strategy of heterologous boosting with injectable or inhaled Ad5-vectored SARS-CoV-2 vaccination of individuals primed with inactivated COVID-19 vaccine.

Long-term air pollution exposure, habitual physical activity, and incident chronic kidney disease.

Both air pollution and physical inactivity contribute to the increased risk of incident chronic kidney disease (CKD). However, the detrimental effects of air pollution exposure could be augmented by an elevated intake of air pollutants during exercise. In the present study, we analyzed 367,978 participants who were CKD-free at baseline (2006-2010) based on the UK Biobank. Air pollutants included fine particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX). Physical activity (PA) was obtained by the self-reported questionnaire. Using Cox proportional hazards models, hazard ratios (HRs) for incident CKD related to air pollution, PA, and incident CKD were evaluated. During a median of 12.4 years of follow-up, 14,191 incident CKD events were documented. High PM2.5, PM10, NO2, and NOX increased CKD risks by 11 %, 15 %, 14 %, and 12 %, respectively, while moderate and high PA reduced CKD risks by 18 % and 22 %, respectively. Participants with high PA and low air pollution exposure had 29 %, 31 %, 30 %, and 30 % risks of incident CKD than those with low PA and high air pollution exposure for the four air pollutants, with multivariable-adjusted HRs of 0.71 (95 % confidence intervals [CI]: 0.65-0.76) for PM2.5, 0.69 (95 % CI: 0.64-0.75) for PM10, 0.70 (95 % CI: 0.64-0.75) for NO2, and 0.70 (95 % CI: 0.64-0.75) for NOX. No clear interactions were observed between each air pollutant exposure and PA (all P for interaction > 0.05). The findings that reducing air pollution exposure and increasing PA were both independently correlated with a diminished risk of incident CKD suggest that PA could be targeted to prevent CKD generally regardless of air pollution levels. Further research is needed in areas polluted moderately and severely to examine our findings.

Electrochemical skin conductance and heart rate variability in patients with non-dialysis chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is very common now and associates with high overall and cardiovascular mortality. Numerous studies have reported that Heart rate variability (HRV) could also be used to detect cardiovascular autonomic dysfunction (CAD). We investigated the association of electrochemical skin conductance (ESC) of EZSCAN results with HRV in non-dialysis CKD patients. METHODS: In a cross-sectional study, we enrolled 248 prevalent non-dialysis CKD patients. Patients underwent a 24-h Holter (CB-2302-A, Bio Instrument, China). A time domain analysis of HRV was performed, and the following parameters were obtained: SDNN, SDANN, rMSSD, pNN50. EZSCAN device (Impeto Medical, Paris, France) measures ESC values of each participants. Mean global skin conductance computed as 0.5 * (reflecting (right + left hand)/2 + (right and left foot)/2). Log transforms data into a normal distribution for statistical analysis. RESULTS: There were 142 males and 106 females included in the present study. Patients' age was 56.6±17.08 years. Logarithm(Log) (global ESC) was independently predicted by age (P<0.01), hypertension history, estimated Glomerular filtration rate (eGFR) and log SDNN (P<0.05). While log SDANN, rMSSD and pNN50 were not independent predictors for log (global ESC). CONCLUSION: Increased global ESC significantly associated with elevated HRV, specifically SDNN in non-dialysis CKD patients. This suggested that global ESC may appear to be an important predictor of CAD, and even could be used as a cardiovascular risk factor in non-dialysis CKD patients.

[Theoretical Verification of Dynamic Lumbar Interspinous Process Stabilization Device with Memory Alloys].

To find an effective method of minimally invasive treatment combining prevention and assistance in the middle zone of conservative treatment and fusion surgery for lumbar degenerative diseases, through the clinical effect observation and the advantage and disadvantage comparison of several commonly used lumbar interspinous dynamic stabilization systems, by analyzing the physiological structure, biomechanics and relevant data of lumbar interspinous processes, based on fully understanding of memory alloy materials, a new dynamic lumbar interspinous fixation device with a memory alloy material has been independently designed and researched, which can not only reconstruct the normal biomechanical characteristics of the lumbar spine and satisfy the normal activities of the human spine, but also avoid damage to the original structure and reduce the incidence of postoperative complications. In addition, the device can be used to optimize the current therapeutic methods. According to our research, the dynamic lumbar interspinous process stabilization device with a memory alloy has theoretically achieved satisfactory results, which can be used to overcome the shortcomings of the existing technology and is superior to the current several dynamic lumbar interspinous process stabilization systems.

THz imaging technique for nondestructive analysis of debonding defects in ceramic matrix composites based on multiple echoes and feature fusion.

We propose a THz nondestructive analysis method based on multiple echoes and feature fusion. Conventionally, it is difficult to identify the debonding defects of the glue layer (II) due to the thin adhesive layer. To this end, a THz propagation model is established, and a quantitative method for determining the thickness of debonding defects based on multiple echoes is presented. The measurement error for preset defect thickness of 500 µm was 4%. Further, for determining the area of debonding defects, a feature fusion imaging algorithm is proposed to realize the lateral recognition of defects and quantitative analysis is used to improve the recognition ability of defects.

Accumulation of Pollutants in Proglacial Lake Sediments: Impacts of Glacial Meltwater and Anthropogenic Activities.

With global warming, the melting of glaciers can result in the release of pollutants into the environment. For remote Alpine lakes, both atmosphere-deposited anthropogenic pollutants and glacier-released pollutants can eventually sink in the sediment. To date, there has, to the best of our knowledge, been no attempt at quantifying the contributions of these processes to the accumulation of pollutants in glacial lake sediment. To fill this gap, a semi-enclosed proglacial lake located in the southern Tibetan Plateau was chosen and a 28 cm sediment core, which can be dated back to 1836, was used to explore the temporal trends of trace elements, Hg, and black carbon (BC) during the past two centuries. Geochemical indicators (Rb/Sr, Ti-Zr-Hf, and sedimentary rate) in sediment showed an overall continuous warming of the lake, while the temporal trends of fluxes of toxic elements and BC were broadly associated with their emission patterns. By using a positive matrix factorization model, the contribution of the anthropogenic source rose from <10% in the 1850s to >40% after the 1980s. However, the signal of glacial meltwater release was also distinct, and the greatest contribution of ice-snow meltwater reached up to 61% in the 1950s. Regarding the most recent two decades, 90% of pollutant deposition in the Tibetan sediment can be attributed to the combined forces of primary emissions and glacial release.

Molecular Evidence of Human Monkeypox Virus Infection, Sierra Leone.

Monkeypox virus is a zoonotic disease endemic to Africa. In 2017, we confirmed a case of human monkeypox virus in Sierra Leone by molecular and serologic methods. Sequencing analysis indicated the virus belongs to the West African clade and data suggest it was likely transmitted by wild animals.

Characterization of Tibetan Soil As a Source or Sink of Atmospheric Persistent Organic Pollutants: Seasonal Shift and Impact of Global Warming.

Background soils are reservoirs of persistent organic pollutants (POPs). After decades of reduced primary emissions, it is now possible that the POPs contained in these reservoirs are being remobilized because of climate warming. However, a comprehensive investigation into the remobilization of POPs from background soil on the largest and highest plateau on Earth, the Tibetan Plateau (TP), is lacking. In this study, a sampling campaign was carried out on the TP at three background sites with different land cover types (forest, meadow and desert). Field measurements of the air-soil exchange of POPs showed that previous prediction using empirical models overestimated the values of the soil-air partitioning coefficient ( KSA), especially for chemicals with KOA > 9. The direction of exchange for γ-HCH, HCB, and PCB-28 overlapped with the air-soil equilibrium range, but with a tendency for volatilization. Their emission fluxes were 720, 2935, and 538 pg m-2 day-1, respectively, and were similar in extent to those observed for background Arctic soil in Norway. Nam Co and Ngari are also permafrost regions, and most chemicals at these two sites exhibited volatilization. This is the first result showing that permafrost can also emit POPs. Seasonally, we found that chemicals tended to be re-emitted from soils to the atmosphere in winter and deposited from the air to the soil in summer. This finding is opposite to most previous results, possibly because of the higher air-soil concentration gradient caused by the prevailing transport of POPs in summer. Climate warming exerts a strong influence on air-soil exchange, with an increase of 1 °C in ambient temperature likely leading to an increase of Tibetan atmospheric inventories of POPs by 60-400%.

Methionine Regulates mTORC1 via the T1R1/T1R3-PLCß-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells.

The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca2+ stimulation and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCß-Ca2+-ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

Hijacking of the jasmonate pathway by the mycotoxin fumonisin B1 (FB1) to initiate programmed cell death in Arabidopsis is modulated by RGLG3 and RGLG4.

The mycotoxin fumonisin B1 (FB1) is a strong inducer of programmed cell death (PCD) in plants, but its underlying mechanism remains unclear. Here, we describe two ubiquitin ligases, RING DOMAIN LIGASE3 (RGLG3) and RGLG4, which control FB1-triggered PCD by modulating the jasmonate (JA) signalling pathway in Arabidopsis thaliana. RGLG3 and RGLG4 transcription was sensitive to FB1. Arabidopsis FB1 sensitivity was suppressed by loss of function of RGLG3 and RGLG4 and was increased by their overexpression. Thus RGLG3 and RGLG4 have coordinated and positive roles in FB1-elicited PCD. Mutated JA perception by coi1 disrupted the RGLG3- and RGLG4-related response to FB1 and interfered with their roles in cell death. Although FB1 induced JA-responsive defence genes, it repressed growth-related, as well as JA biosynthesis-related, genes. Consistently, FB1 application reduced JA content in wild-type plants. Furthermore, exogenously applied salicylic acid additively suppressed JA signalling with FB1 treatment, suggesting that FB1-induced salicylic acid inhibits the JA pathway during this process. All of these effects were attenuated in rglg3 rglg4 plants. Altogether, these data suggest that the JA pathway is hijacked by the toxin FB1 to elicit PCD, which is coordinated by Arabidopsis RGLG3 and RGLG4.

Nano-Enhanced Phase Reinforced Magnesium Matrix Composites: A Review of the Matrix, Reinforcement, Interface Design, Properties and Potential Applications.

Magnesium matrix composites are essential lightweight metal matrix composites, following aluminum matrix composites, with outstanding application prospects in automotive, aerospace lightweight and biomedical materials because of their high specific strength, low density and specific stiffness, good casting performance and rich resources. However, the inherent low plasticity and poor fatigue resistance of magnesium hamper its further application to a certain extent. Many researchers have tried many strengthening methods to improve the properties of magnesium alloys, while the relationship between wear resistance and plasticity still needs to be further improved. The nanoparticles added exhibit a good strengthening effect, especially the ceramic nanoparticles. Nanoparticle-reinforced magnesium matrix composites not only exhibit a high impact toughness, but also maintain the high strength and wear resistance of ceramic materials, effectively balancing the restriction between the strength and toughness. Therefore, this work aims to provide a review of the state of the art of research on the matrix, reinforcement, design, properties and potential applications of nano-reinforced phase-reinforced magnesium matrix composites (especially ceramic nanoparticle-reinforced ones). The conventional and potential matrices for the fabrication of magnesium matrix composites are introduced. The classification and influence of ceramic reinforcements are assessed, and the factors influencing interface bonding strength between reinforcements and matrix, regulation and design, performance and application are analyzed. Finally, the scope of future research in this field is discussed.

Cognitive dysfunction in schizophrenia patients caused by down-regulation of γ-aminobutyric acid receptor subunits.

BACKGROUND: The expression pattern of gamma aminobutyric acid (GABA) receptor subunits are commonly altered in patients with schizophrenia, which may lead to nerve excitation/inhibition problems, affecting cognition, emotion, and behavior. AIM: To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments. METHODS: This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period. The expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance spectroscopy. The recognized cognitive battery tool, the MATRICS Consensus Cognitive Battery, was used to evaluate the scores for various dimensions of cognitive function. The correlation between GABA receptor subunit downregulation and schizophrenia was also analyzed. RESULTS: Significant differences in GABA receptor subunit levels were found between the case and control groups (P < 0.05). A significant difference was also found between the case and control groups in terms of cognitive function measures, including attention/alertness and learning ability (P < 0.05). Specifically, as the expression levels of GABRA1 (α1 subunit gene), GABRB2 (ß2 subunit gene), GABRD (δ subunit), and GABRE (ε subunit) decreased, the severity of the patients' condition increased gradually, indicating a positive correlation between the downregulation of these 4 receptor subunits and schizophrenia (P < 0.05). However, the expression levels of GABRA5 (α5 subunit gene) and GABRA6 (α6 subunit gene) showed no significant correlation with schizophrenia (P > 0.05). CONCLUSION: Downregulation of the GABA receptor subunits is positively correlated with schizophrenia. In other words, when GABA receptor subunits are downregulated in patients, cognitive impairment becomes more severe.

S-9-PAHSA's neuroprotective effect mediated by CAIII suppresses apoptosis and oxidative stress in a mouse model of type 2 diabetes.

BACKGROUND: With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S-9-PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S-9-PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear. METHODS: This in vivo study in mice fed a high-fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S-9-PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S-9-PAHSA on cognition in the mice, while the neuroprotective effect of S-9-PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an in vitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S-9-PAHSA. RESULTS: S-9-PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S-9-PAHSA protected both neuronal cells and microvascular endothelial cells in in vivo and in vitro diabetic environments. Interestingly, this protective effect of S-9-PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S-9-PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S-9-PAHSA. CONCLUSION: S-9-PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S-9-PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.

Two novel RING-type ubiquitin ligases, RGLG3 and RGLG4, are essential for jasmonate-mediated responses in Arabidopsis.

Jasmonates (JAs) regulate various stress responses and development processes in plants, and the JA pathway is tightly controlled. In this study, we report the functional characterization of two novel RING-type ubiquitin ligases, RING DOMAIN LIGASE3 (RGLG3) and RGLG4, in modulating JA signaling. Both RGLG3 and RGLG4 possessed ubiquitin ligase activities and were widely distributed in Arabidopsis (Arabidopsis thaliana) tissues. Altered expression of RGLG3 and RGLG4 affected methyl JA-inhibited root growth and JA-inductive gene expression, which could be suppressed by the coronatine insensitive1 (coi1) mutant. rglg3 rglg4 also attenuated the inhibitory effect of JA-isoleucine-mimicking coronatine on root elongation, and consistently, rglg3 rglg4 was resistant to the coronatine-secreting pathogen Pseudomonas syringae pv tomato DC3000, suggesting that RGLG3 and RGLG4 acted in response to the coronatine and promoted JA-mediated pathogen susceptibility. In addition, rglg3 rglg4 repressed wound-stunted plant growth, wound-stimulated expression of JA-responsive genes, and wound-induced JA biosynthesis, indicating their roles in JA-dependent wound response. Furthermore, both RGLG3 and RGLG4 responded to methyl JA, P. syringae pv tomato DC3000, and wounding in a COI1-dependent manner. Taken together, these results indicate that the ubiquitin ligases RGLG3 and RGLG4 are essential upstream modulators of JA signaling in response to various stimuli.

Comparison of clinical outcomes and prognosis between total pancreatectomy and pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis.

BACKGROUND: To compare the clinical outcomes and prognosis of total pancreatectomy (TP) and pancreaticoduodenectomy (PD) for the treatment of pancreatic ductal adenocarcinoma (PDAC), and to explore the safety and indications of TP. METHODS: A systematic search was conducted on PubMed, Web of Science, and Embase databases from January 1943 to March 2023 for literatures comparing TP and PD in the treatment of PDAC. The primary outcome was postoperative overall survival (OS), and secondary outcomes included surgery time, blood loss, readmission, hospital stay, perioperative mortality, and overall morbidity. Fixed-effect or random-effect models were selected based on heterogeneity, and odds ratio (OR), mean difference (MD), or hazard ratio (HR) with 95% confidence intervals (CI) were calculated. RESULTS: A total of six studies involving 8396 patients were included in the meta-analysis. There was no statistically significant difference in OS after surgery between the two groups (HR = 1.08, 95% CI: 0.91-1.27; P = 0.38). The TP group had a longer surgery time (MD = 13.66, 95% CI: 4.57-22.75; P = 0.003) and more blood loss (MD = 133.17, 95% CI: 8.00-258.33; P = 0.04) than the PD group. There were no significant differences between the two groups in terms of hospital stay (MD = 0.09, 95% CI: -2.04 to 2.22; P = 0.93), readmission rate (OR = 1.39; 95% CI: 1.00-1.92; P = 0.05), perioperative mortality (OR = 1.29, 95% CI: 0.98-1.69; P = 0.07), and overall morbidity (OR = 0.80, 95% CI: 0.50-1.26; P = 0.33). CONCLUSION: The surgical process of TP is relatively complex, but there is no difference in short-term clinical outcomes and OS compared to PD, making it a safe and reliable procedure. Indications and treatment outcomes for planned TP and salvage TP may differ, and more research is needed in the future for further classification and verification.

Occurrence, spatial heterogeneity, and risk assessment of perfluoroalkyl acids (PFAAs) in the major rivers of the Tibetan Plateau.

The Tibetan Plateau (TP) is home to the headwaters of major rivers in Asia, yet their water quality security on a large spatial scale is scarcely studied, especially in regard to emerging organic pollutants. In this study, a systematic field campaign was carried out along Yarlung Tsangpo River, Nu River, Lancang River and Jinsha River, and 13 perfluoroalkyl acids (PFAAs) were analyzed. The total concentrations of PFAAs in the river waters of the TP were in the range of 0.58-7.46 ng/L, containing a high proportion of perfluorobutanoic acid (PFBA) and perfluorobutane sulfonate (PFBS) with average values of 56.7 %. Elevated PFAA loadings were found for the midstream of Yarlung Tsangpo River in central Tibet. Geodetector results indicated that precipitation, solar radiation and vegetation type were the top three influential factors contributing to the observed spatial heterogeneity. When interactions with human activities were taken into account, the explanatory power was significantly enhanced and rose above 0.70, highlighting the increased risks for TP rivers from the combined effects of natural environments and anthropogenic activities. Risk assessments suggest a low risk is posed to the alpine aquatic ecosystems and human health. The discharge fluxes of PFAAs via riverine export were estimated at 94-425 kg/year, which is one to two orders of magnitude lower than their mass loadings in major rivers worldwide. Our study underlined the need for further attention to the increased risk of water resource quality on the central TP in the context of long-range transport, increased cryosphere melting and local emission.

Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice.

Current COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a replication-competent recombinant chimeric influenza A virus (IAV) expressing the receptor-binding domain (RBD) of a SARS-CoV-2 prototype in the C-terminus of the neuraminidase (NA) of A/Puerto Rico/08/1934 H1N1 (PR8). The remaining seven segments from A/WSN/1933 H1N1 (WSN) were named PR8NARBD/WSN. We observed that the recombinant virus with the WSN backbone demonstrated improved expression of NA and RBD. A single intranasal dose of PR8NARBD/WSN(103PFU) in mice generated robust mucosal immunity, neutralising antibodies, cellular immunity, and tissue-resident memory T cells specific to SARS-CoV-2 and IAV. Importantly, immunisation with PR8NARBD/WSN viruses effectively protected mice against lethal challenges with H1N1, H3N2 IAV, and SARS-CoV-2 Beta variant and significantly reduced lung viral loads. Overall, our research demonstrates the promising potential of PR8NARBD/WSN as an attractive vaccine against emerging SARS-CoV-2 variants and influenza A virus infections.

Association of Night Shifts and Lifestyle Risks With Incident Dementia.

BACKGROUND: Little is known about the combined relationship between night shifts and lifestyle risks with incident dementia or their potential interactions. To evaluate the association of night shifts and lifestyle risks with incident dementia and further analyze their interactions. METHODS: A total of 276 059 participants were included in this study from the UK Biobank cohort. Cox proportional hazards models were used to investigate the combined association of night shifts and lifestyle risks with incident dementia. RESULTS: Participants with always night shifts and 3 or 4 unhealthy lifestyle factors had the highest risk of incident all-cause dementia (hazard ratio: 3.15, 95% confidence interval [CI]: 1.74-5.69). An additive interaction was found between night shifts and lifestyle risks for incident all-cause dementia (p < .001), with a relative excess risk due to the interaction of 0.14 (95% CI: 0.11-0.45). The attributable proportions of the combined effect on the incidence of all-cause dementia were 22.6% (95% CI: 20.91%-26.75%) for night shift work, 65.0% (95% CI: 63.12%-69.80%) for unhealthy lifestyle factors, and 12.1% (95% CI: 8.67%-18.04%) for their interaction. CONCLUSIONS: Both night shifts and lifestyle risks were associated with a higher risk of incident dementia. The combined impact was higher than the increase in the risks related to each single factor. Our results indicated that most incident dementia cases might be prevented by a healthy lifestyle, and the benefits would be greater among night shift workers. Further studies are needed to confirm our results and explore the underlying mechanisms.