Molecular Modeling of Shockwave-Mediated Blood-Brain Barrier Opening for Targeted Drug Delivery.

Bubble-enhanced shock waves induce the transient opening of the blood-brain barrier (BBB) providing unique advantages for targeted drug delivery of brain tumor therapy, but little is known about the molecular details of this process. Based on our BBB model including 28 000 lipids and 280 tight junction proteins and coarse-grained dynamics simulations, we provided the molecular-level delivery mechanism of three typical drugs for the first time, including the lipophilic paclitaxel, hydrophilic gemcitabine, and siRNA encapsulated in liposome, across the BBB. The results show that the BBB is more difficult to be perforated by shock-induced jets than the human brain plasma membrane (PM), requiring higher shock wave speeds. For the pores formed, the BBB exhibits a greater ability to self-heal than PM. Hydrophobic paclitaxel can cross the BBB and be successfully absorbed, but the amount is only one-third of that of PM; however, the absorption of hydrophilic gemcitabine was almost negligible. Liposome-loaded siRNAs only stayed in the first layer of the BBB. The mechanism analysis shows that increasing the bubble size can promote drug absorption while reducing the risk of higher shock wave overpressure. An exponential function was proposed to describe the relation between bubble and overpressure, which can be extended to the experimental microbubble scale. The calculated overpressure is consistent with the experimental result. These molecular-scale details on shock-assisted BBB opening for targeted drug delivery would guide and assist experimental attempts to promote the application of this strategy in the clinical treatment of brain tumors.

Implications of perceived empathy from spouses during pregnancy for health-related quality of life among pregnant women: a cross-sectional study in Anhui, China.

BACKGROUND: Empathy is a critical component of nursing care, impacting both nurses' and patients' outcomes. However, perceived empathy from spouses during pregnancy and its impact on health-related quality of life (HRQoL) are unclear. This study aimed to examine pregnant women's perceived empathy from their spouses and assess the relation of perceived empathy on HRQoL. METHODS: This cross-sectional study, performed in the obstetric clinics or wards of four well-known hospitals in Anhui Province, China, included 349 pregnant women in the second or third trimester; participants were recruited by convenience sampling and enrolled from October to December 2021. A general information questionnaire, the Interpersonal Reactivity Index (IRI), a purpose-designed empathy questionnaire and the Medical Outcomes Study 12-item Short-Form Health Survey (SF-12) were used to evaluate the pregnant women's general information, perceptions of empathy and HRQoL. Data were analysed using SPSS 22 at a threshold of P < 0.05. Descriptive analysis, Pearson correlation analysis, Student's t test, ANOVA, and multiple regression analysis were used for analysis. RESULTS: The pregnant women's total empathy, physical component summary (PCS) and mental component summary (MCS) scores were 41.6 ± 9.0, 41.6 ± 7.6, and 47.7 ± 9.1, respectively. Correlation analysis revealed that the purpose-designed empathy questionnaire items were significantly positively correlated with perspective taking and empathic concern but were not correlated with the personal distress dimension and were only partially correlated with the fantasy dimension. Maternal physical condition during pregnancy, planned pregnancy, and occupational stress were predictors of the PCS score (ß = 0.281, P < 0.01; ß = 0.132, P = 0.02; ß = -0.128, P = 0.02). The behavioural empathy item of our purpose-designed empathy questionnaire and empathic concern were important predictors of the MCS score (ß = 0.127, P = 0.02; ß = 0.158, P < 0.01), as well as other demographic and obstetric information, explaining 22.0% of the variance in MCS scores totally (F = 12.228, P < 0.01). CONCLUSIONS: Pregnant women perceived lower empathy from their spouses and reported lower HRQoL. Perceived empathy, particularly behavioural empathy, may significantly impact pregnant women's MCS scores but has no effect on their PCS scores. Strategies that foster perceived empathy from spouses among pregnant women are essential for facilitating healthy pregnancies and potentially improving maternal and child health.

Characteristics and risk factors for invasive fungal infection in hospitalized patients with acute-on-chronic hepatitis B liver failure: a retrospective cohort study from 2010 to 2023.

Background and aim: The global burden of invasive fungal infections (IFIs) is emerging in immunologic deficiency status from various disease. Patients with acute-on-chronic hepatitis B liver failure (ACHBLF) are prone to IFI and their conditions are commonly exacerbated by IFI. However, little is known about the characteristics and risk factors for IFI in hospitalized ACHBLF patients. Methods: A total of 243 hospitalized ACHBLF patients were retrospectively enrolled from January 2010 to July 2023. We performed restricted cubic spline analysis to determine the non-linear associations between independent variables and IFI. The risk factors for IFI were identified using logistic regression and the extreme gradient boosting (XGBoost) algorithm. The effect values of the risk factors were determined by the SHapley Additive exPlanations (SHAP) method. Results: There were 24 ACHBLF patients (9.84%) who developed IFI on average 17.5 (13.50, 23.00) days after admission. The serum creatinine level showed a non-linear association with the possibility of IFI. Multiple logistic regression revealed that length of hospitalization (OR = 1.05, 95% CI: 1.02-1.08, P = 0.002) and neutrophilic granulocyte percentage (OR = 1.04, 95% CI: 1.00-1.09, P = 0.042) were independent risk factors for IFI. The XGBoost algorithm showed that the use of antibiotics (SHAP value = 0.446), length of hospitalization (SHAP value = 0.406) and log (qHBV DNA) (SHAP value = 0.206) were the top three independent risk factors for IFI. Furthermore, interaction analysis revealed no multiplicative effects between the use of antibiotics and the use of glucocorticoids (P = 0.990). Conclusion: IFI is a rare complication that leads to high mortality in hospitalized ACHBLF patients, and a high neutrophilic granulocyte percentage and length of hospitalization are independent risk factors for the occurrence of IFI.

Comparison of singleton and twin birth weight reference percentile curves by gestational age and sex in extremely preterm infants: a population-based study.

BACKGROUND: With the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth weight percentile curves for singletons and twins in EPIs from China and the USA and compare the differences between them. METHODS: In China, EPIs were from 31 provinces, from 2010 to 2021. The collected information was sex, gestational age, birth weight, singletons and twins. We used the generalised additive models for location scale and shape method to construct the birth weight percentile curves by gestational age and sex for EPIs. The National Vital Statistics System database from 2016 to 2021 was also analysed. We compared the differences between the 50th birth weight percentile curves of the two databases. RESULTS: We identified 8768 neonates in China (5536 singletons and 3232 twins) and 121 933 neonates in the USA (97 329 singletons and 24 604 twins). We established the 3rd, 10th, 25th, 50th, 75th, 90th and 97th birth weight reference curves for China and the USA. The results showed that males had higher birth weights than females. In China, for the same gestational age and sex, birth weights in singletons and twins were found to be similar, though singleton males born in China had slightly higher birth weights than male twins. In the USA, birth weights were also similar for females and males, with the same gestational age in singletons and twins. CONCLUSION: We established birth weight reference percentile curves by gestational age and sex for singletons and twins among EPIs in China and the USA.

Construction of Adaptive Deformation Block: Rational Molecular Editing of the N-Rich Host Molecule to Remove Water from the Energetic Hydrogen-Bonded Organic Frameworks.

Energetic hydrogen-bonded organic frameworks (E-HOFs), as a type of energetic material, spark fresh vitality to the creation of high energy density materials (HEDMs). However, E-HOFs containing cations and anions face challenges such as reduced energy density due to the inclusion of crystal water. In this work, the modification of amino groups in N-rich organic units could form a smart building block of hydrogen-bonded frameworks capable of changing the volume of the void space in the molecule through adaptive deformation of E-MOF blocks, thus enabling the replacement of water. Based on the above strategy, we report an interesting example of a series of hydrogen-bonded organic frameworks (E-HOF 2a and 3a) synthesized using a facile method. The crystal structure data of all of the compounds were also obtained in this work. Anhydrous 2a and 3a exhibit higher density, good thermal stability, and low mechanical sensitivity. The strategy of covalent bond modification for the host molecules of energetic frameworks shows enormous potential in eliminating the crystalline H2O of hydration and exploring high energy density materials.

Double Discrete Cosine Transform-Oriented Multi-View Subspace Clustering.

Low-rank tensor representation with the tensor nuclear norm has been rising in popularity in multi-view subspace clustering (MVSC), in which the tensor nuclear norm is commonly implemented using discrete Fourier transform (DFT). Unfortunately, existing DFT-oriented MVSC methods may provide unsatisfactory results since (1) DFT exploits complex arithmetic in the Fourier domain, usually resulting in high tubal tensor rank, and (2) local structural information is rarely considered. To solve these problems, in this paper, we propose a novel double discrete cosine transform (DCT)-oriented multi-view subspace clustering (D2CTMSC) method, in which the first DCT aims to derive the tensor nuclear norm without complex arithmetic while the second DCT aims to explore the local structure of the self-representation tensor, such that the essential low-rankness and sparsity embedding in multi-view features can be thoroughly exploited. Moreover, we design an effective alternating iteration strategy to solve the proposed model. Experimental results on four types of multi-view datasets (News stories, Face images, Scene images, and Generic objects) demonstrate the superiority of the D2CTMSC method compared with DFT-based methods and other state-of-the-art clustering methods.

Impact of delayed diagnosis and treatment on tuberculosis infection within families: A case report.

BACKGROUND: A 32-year-old male patient was diagnosed with a 30% left pneumothorax on November 5, 2020, during which chest imaging indicated abnormalities. Despite this, pulmonary tuberculosis (TB) was not diagnosed or treated at that time due to a negative result in the MGIT960 culture. The patient experienced symptoms of cough and expectoration on April 24, 2022. Upon repeating the chest imaging, the condition had worsened, confirming the presence of pulmonary TB, leading to the patient's hospitalization. On September 1, 2022, the 11-year-old daughter of the patient was diagnosed with pulmonary tuberculosis accompanied by bronchial tuberculosis and tuberculous pleurisy. METHODS: The diagnosis of pulmonary tuberculosis was confirmed through sputum smears and Gene Xpert MTB/RIF testing, for the patient and his 11-year-old daughter in 2022. The patient underwent a 6-month combination therapy (2HRZE/4HR) comprising isoniazid, rifampicin, pyrazinamide, and ethambutol. His daughter with pulmonary tuberculosis accompanied by bronchial tuberculosis and tuberculous pleurisy underwent a 12-month combination therapy. RESULTS: Late diagnosis and treatment delays contribute to tuberculosis infections within families. Fortunately, after more than 3 months of antituberculosis treatment, the patient experienced relief from cough and sputum secretion, and there was improvement observed in the chest CT scan. Six months later, the patient was successfully cured of TB. 12 months later, his daughter also was successfully cured of TB. CONCLUSION SUBSECTIONS: Early diagnosis and treatment of tuberculosis (TB) is vital to reduce transmission, morbidity, and mortality.

RCUMP: Residual Completion Unrolling With Mixed Priors for Snapshot Compressive Imaging.

Deep unrolling-based snapshot compressive imaging (SCI) methods, which employ iterative formulas to construct interpretable iterative frameworks and embedded learnable modules, have achieved remarkable success in reconstructing 3-dimensional (3D) hyperspectral images (HSIs) from 2D measurement induced by coded aperture snapshot spectral imaging (CASSI). However, the existing deep unrolling-based methods are limited by the residuals associated with Taylor approximations and the poor representation ability of single hand-craft priors. To address these issues, we propose a novel HSI construction method named residual completion unrolling with mixed priors (RCUMP). RCUMP exploits a residual completion branch to solve the residual problem and incorporates mixed priors composed of a novel deep sparse prior and mask prior to enhance the representation ability. Our proposed CNN-based model can significantly reduce memory cost, which is an obvious improvement over previous CNN methods, and achieves better performance compared with the state-of-the-art transformer and RNN methods. In this work, our method is compared with the 9 most recent baselines on 10 scenes. The results show that our method consistently outperforms all the other methods while decreasing memory consumption by up to 80%.

Hyperglycemia in pregnancy did not worsen the short-term outcomes of very preterm infants: a propensity score matching study.

Background: Hyperglycemia in pregnancy (HGP) has generally been considered a risk factor associated with adverse outcomes in offspring, but its impact on the short-term outcomes of very preterm infants remains unclear. Methods: A secondary analysis was performed based on clinical data collected prospectively from 28 hospitals in seven regions of China from September 2019 to December 2020. According to maternal HGP, all infants were divided into the HGP group or the non-HGP group. A propensity score matching analysis was used to adjust for confounding factors, including gestational age, twin or multiple births, sex, antenatal steroid administration, delivery mode and hypertensive disorders of pregnancy. The main complications and the short-term growth status during hospitalization were evaluated in the HGP and non-HGP groups. Results: A total of 2,514 infants were eligible for analysis. After matching, there were 437 infants in the HGP group and 874 infants in the non-HGP group. There was no significant difference between the two groups in main complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, culture positive sepsis, intraventricular hemorrhage, periventricular leukomalacia, anemia, feeding intolerance, metabolic bone disease of prematurity, or parenteral nutrition-associated cholestasis. The incidences of extrauterine growth retardation and increased growth retardation for weight and head circumference in the non-HGP group were all higher than those in the HGP group after matching (P < 0.05). Conclusions: HGP did not worsen the short-term outcomes of the surviving very preterm infants, as it did not lead to a higher risk of the main neonatal complications, and the infants' growth improved during hospitalization.

How Microbubble-Enhanced Shock Waves Promote the Delivery of Lipid-siRNA across Neuronal Plasma Membrane: A Computational Study.

In this computational study, we examine the potential of microbubble-enhanced shock waves to improve the delivery of lipid-siRNA nanoparticles across neuronal plasma membranes with the ultimate aim of enhancing brain tumor treatment. We critically evaluate several variables related to experiments, including the bubble size, the shock speed and action time, and the amount of siRNA encapsulated in the liposome. Our findings reveal that microbubble-enhanced shock waves are essential for the high delivery of small lipid vesicles (under 30 nm diameter); its corresponding variables significantly impact drug penetration and absorption rates and influence the overall efficacy of the drug delivery system. Long-time recovery simulations further provide valuable insights into the self-healing ability of the plasma membrane following shock wave exposure and the subsequent absorption dynamics of siRNA. This work provides the dynamic process of siRNA released from lipid vesicles with shock wave and nanobubbles, thereby serving as a molecular mechanism support for developing tunable delivery systems for RNA-based therapy in brain tumors.

A longitudinal study on the change in sleep across three waves of the COVID-19 outbreaks in Hong Kong.

In the year 2020, Hong Kong experienced four COVID-19 epidemic waves. The present study aimed to examine the transition of sleep disturbances and explore its associated factors across the later three epidemic waves. Among the 1138 respondents who participated in an online survey at the second wave (T1, April 2020), 338 and 378 participants also completed a follow-up at the third (T2, August 2020) and fourth waves (T3, December 2020), respectively. Participants completed the Insomnia Severity Index and an investigator-designed questionnaire regarding potential factors associated with sleep change such as perceived risk of being infected, economic stress, and confidence in the government and health care professional. Sample of this study were mainly female (67.7%), married (50.3%), young adults (54.2%) with tertiary education (81.6%). Maintaining normal sleep was the most prevalent trajectory of sleep of all three waves (50.5%), followed by persistent insomnia (17.2%) and remitted insomnia (9.0%). Besides female, older-age and lower education level, the results showed that increment in worry about family being infected (adjusted risk ratio, RR = 1.28), perceived interference of daily lives (adjusted RR = 1.19), and economic distress (adjusted RR = 1.24) were significantly associated with the development of clinical insomnia during the three epidemic waves. These factors were also associated with worsening of other sleep parameters. Insomnia being persistent across the three waves of COVID-19 outbreaks was common. Increasing economic distress, daily interference, and worry about family members being infected were associated with an increasing risk of clinical insomnia across the three COVID-19 outbreaks. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00486-w.

Comparable prognosis of early gastric cancer between intestinal type and diffuse type in patients of age 75 and older: a SEER-based cohort study.

Background: The prognostic significance of Lauren's classification in elderly early gastric cancer (EGC) patients remains largely unknown. We aim to investigate the characteristics and clinical implications of Lauren's classification in elderly EGC patients. Methods: Patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database based on the inclusion and exclusion criteria. Univariate and multivariate Cox regression, propensity score matching, inverse-probability-weighted analysis, and propensity-score adjustment were utilized to evaluate the association between Lauren's classification and cancer-specific survival (CSS) in elderly EGC patients. Stratification and interaction analyses were used to reveal the effects of confounding factors on the association between Lauren's classification and CSS. Results: The diffuse type (median, 41.0 months) showed a similar survival (37.0 months), and was mainly distributed in female group (62.5% vs. 42.2%) with poorly differentiated or undifferentiated components (89.1% vs. 27.0%) compared with intestinal type in elderly EGC patients. Analyses of univariate and multivariate Cox regression, propensity score matching, inverse-probability-weighted analysis, and propensity-score adjustment showed that Lauren's classification was not significantly CSS in elderly EGC patients (P>0.05). Subgroup and interaction analyses confirmed the stability of the results. Conclusions: Diffuse type was mainly distributed in female patients with more poorly differentiated/undifferentiated components and similar prognosis compared with intestinal type in age 75 and older EGC patients. No significant association was observed between diffuse type and CSS of the elderly EGC patients.

The role of nutrition in analysis of risk factors and short-term outcomes for late-onset necrotizing enterocolitis among very preterm infants: a nationwide, multicenter study in China.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. METHOD: Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. RESULTS: Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation. CONCLUSION: Actively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs. TRIAL REGISTRATION: ChiCTR1900023418 (26/05/2019).

MRI-Based Machine Learning Fusion Models to Distinguish Encephalitis and Gliomas.

This paper aims to compare the performance of the classical machine learning (CML) model and the deep learning (DL) model, and to assess the effectiveness of utilizing fusion radiomics from both CML and DL in distinguishing encephalitis from glioma in atypical cases. We analysed the axial FLAIR images of preoperative MRI in 116 patients pathologically confirmed as gliomas and clinically diagnosed with encephalitis. The 3 CML models (logistic regression (LR), support vector machine (SVM) and multi-layer perceptron (MLP)), 3 DL models (DenseNet 121, ResNet 50 and ResNet 18) and a deep learning radiomic (DLR) model were established, respectively. The area under the receiver operating curve (AUC) and sensitivity, specificity, accuracy, negative predictive value (NPV) and positive predictive value (PPV) were calculated for the training and validation sets. In addition, a deep learning radiomic nomogram (DLRN) and a web calculator were designed as a tool to aid clinical decision-making. The best DL model (ResNet50) consistently outperformed the best CML model (LR). The DLR model had the best predictive performance, with AUC, sensitivity, specificity, accuracy, NPV and PPV of 0.879, 0.929, 0.800, 0.875, 0.867 and 0.889 in the validation sets, respectively. Calibration curve of DLR model shows good agreement between prediction and observation, and the decision curve analysis (DCA) indicated that the DLR model had higher overall net benefit than the other two models (ResNet50 and LR). Meanwhile, the DLRN and web calculator can provide dynamic assessments. Machine learning (ML) models have the potential to non-invasively differentiate between encephalitis and glioma in atypical cases. Furthermore, combining DL and CML techniques could enhance the performance of the ML models.

A simple and effective method to enrich endogenous DNA from mammalian faeces.

Utilization of faeces has long been a popular approach for genetic and ecological studies of wildlife. However, the success of molecular marker genotyping and genome resequencing is often unpredictable due to insufficient enrichment of endogenous DNA in the total faecal DNA that is dominated by bacterial DNA. Here, we report a simple and cheap method named PEERS to predominantly lyse animal cells over bacteria by using sodium dodecyl sulphate so as to discharge endogenous DNA into liquid phase before bacterial DNA. By brief centrifugation, total DNA with enriched endogenous fraction can be extracted from the supernatant using routine methods. Our assessments showed that the endogenous DNA extracted by PEERS was significantly enriched for various types of faeces from different species, preservation time and conditions. It significantly improves the genotyping correctness and efficiency of genome resequencing with the total additional cost of $ 0.1 and a short incubation step to treat a faecal sample. We also provide methods to assess the enrichment efficiency of mitochondrial and nuclear DNA and models to predict the usability of faecal DNA for genotyping of short tandem repeat, single-nucleotide polymorphism and whole-genome resequencing.

Gene-based association tests in family samples using GWAS summary statistics.

Genome-wide association studies (GWAS) have led to rapid growth in detecting genetic variants associated with various phenotypes. Owing to a great number of publicly accessible GWAS summary statistics, and the difficulty in obtaining individual-level genotype data, many existing gene-based association tests have been adapted to require only GWAS summary statistics rather than individual-level data. However, these association tests are restricted to unrelated individuals and thus do not apply to family samples directly. Moreover, due to its flexibility and effectiveness, the linear mixed model has been increasingly utilized in GWAS to handle correlated data, such as family samples. However, it remains unknown how to perform gene-based association tests in family samples using the GWAS summary statistics estimated from the linear mixed model. In this study, we show that, when family size is negligible compared to the total sample size, the diagonal block structure of the kinship matrix makes it possible to approximate the correlation matrix of marginal Z scores by linkage disequilibrium matrix. Based on this result, current methods utilizing summary statistics for unrelated individuals can be directly applied to family data without any modifications. Our simulation results demonstrate that this proposed strategy controls the type 1 error rate well in various situations. Finally, we exemplify the usefulness of the proposed approach with a dental caries GWAS data set.

A genome and gene catalog of the aquatic microbiomes of the Tibetan Plateau.

The Tibetan Plateau supplies water to nearly 2 billion people in Asia, but climate change poses threats to its aquatic microbial resources. Here, we construct the Tibetan Plateau Microbial Catalog by sequencing 498 metagenomes from six water ecosystems (saline lakes, freshwater lakes, rivers, hot springs, wetlands and glaciers). Our catalog expands knowledge of regional genomic diversity by presenting 32,355 metagenome-assembled genomes that de-replicated into 10,723 representative genome-based species, of which 88% were unannotated. The catalog contains nearly 300 million non-redundant gene clusters, of which 15% novel, and 73,864 biosynthetic gene clusters, of which 50% novel, thus expanding known functional diversity. Using these data, we investigate the Tibetan Plateau aquatic microbiome's biogeography along a distance of 2,500 km and >5 km in altitude. Microbial compositional similarity and the shared gene count with the Tibetan Plateau microbiome decline along with distance and altitude difference, suggesting a dispersal pattern. The Tibetan Plateau Microbial Catalog stands as a substantial repository for high-altitude aquatic microbiome resources, providing potential for discovering novel lineages and functions, and bridging knowledge gaps in microbiome biogeography.

A seven-sex species recognizes self and non-self mating-type via a novel protein complex.

Although most species have two sexes, multisexual (or multi-mating type) species are also widespread. However, it is unclear how mating-type recognition is achieved at the molecular level in multisexual species. The unicellular ciliate Tetrahymena thermophila has seven mating types, which are determined by the MTA and MTB proteins. In this study, we found that both proteins are essential for cells to send or receive complete mating-type information, and transmission of the mating-type signal requires both proteins to be expressed in the same cell. We found that MTA and MTB form a mating-type recognition complex that localizes to the plasma membrane, but not to the cilia. Stimulation experiments showed that the mating-type-specific regions of MTA and MTB mediate both self- and non-self-recognition, indicating that T. thermophila uses a dual approach to achieve mating-type recognition. Our results suggest that MTA and MTB form an elaborate multifunctional protein complex that can identify cells of both self and non-self mating types in order to inhibit or activate mating, respectively.

Healthy aging trajectories and their predictors among Chinese older adults: Evidence from a 7-year nationwide prospective cohort study.

OBJECTIVES: This study aimed to identify healthy aging trajectories of Chinese older adults, and explore the factors contributing to these trajectories. METHODS: We used data from four waves (2011-2018) of China Health and Retirement Longitudinal Study. We developed a healthy aging metric based on the healthy aging framework of World Health Organization (WHO) and Bayesian multilevel item response theory (IRT) method. The healthy aging trajectories were identified using the latent class growth analysis. The predictors of trajectories were explored using multinomial logistic regression analysis. Additionally, we developed two alternative metrics for healthy aging based on the Chinese Healthy Ageing Index (CHAI) and Rowe and Kahn's model of successful aging, respectively. We compared these metrics to the one developed based on the WHO's healthy aging framework. RESULTS: We identified three distinct healthy aging trajectories with varying scores and decline rates. Individuals who were female, had lower educational levels, resided in rural areas, experienced depression, had more chronic diseases, participated in fewer social activities, had fewer childhood friends, experienced more adverse childhood events, and had worse family financial status in childhood were more likely to experience a worse healthy aging trajectory compared to their counterparts. Supplementary analysis showed that healthy aging metric based on WHO definition and IRT method had the strongest association with health outcomes compared to the metrics based on CHAI, as well as Rowe and Kahn model. CONCLUSIONS: Our findings provide a foundation for the development of tailored interventions to enhance and sustain healthy aging among Chinese older adults.