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Background Checkpoint-blockade immunotherapy targeting programmed cell death protein 1 (PD-1) has recently shown promising efficacy in hepatocellular carcinoma (HCC). However, the factors affecting and predicting the response to anti-PD-1 immunotherapy in HCC are still unclear. Herein, we report the dynamic variation characteristics and specificities of the gut microbiome during anti-PD-1 immunotherapy in HCC using metagenomic sequencing. Results Fecal samples from patients responding to immunotherapy showed higher taxa richness and more gene counts than those of non-responders. For dynamic analysis during anti-PD-1 immunotherapy, the dissimilarity of beta diversity became prominent across patients as early as Week 6. In non-responders, Proteobacteria increased from Week 3, and became predominant at Week 12. Twenty responder-enriched species, including Akkermansia muciniphila and Ruminococcaceae spp., were further identified. The related functional genes and metabolic pathway analysis, such as carbohydrate metabolism and methanogenesis, verified the potential bioactivities of responder-enriched species. Conclusions Gut microbiome may have a critical impact on the responses of HCC patients treated with anti-PD-1 immunotherapy. The dynamic variation characteristics of the gut microbiome may provide early predictions of the outcomes of immunotherapy in HCC, which is critical for disease-monitoring and treatment decision-making.

AbstractMesenchymal stem cells (MSCs) can sense and convert mechanical stimuli signals into a chemical response. Integrins are involved in the mechanotransduction from inside to outside and from outside to inside, and ultimately affect the fate of MSCs responding to different mechanical signals. Different integrins participate in different signaling pathways to regulate MSCs multi-differentiation. In this review, we summarize the latest advances in the effects of mechanical signals on the differentiation of MSCs, the importance of integrins in mechanotransduction, the relationship between integrin heterodimers and different mechanical signals, and the interaction among mechanical signals. We put forward our views on the prospect and challenges of developing mechanical biology in tissue engineering and regenerative medicine.

Background Microbial flocculation is a good choice for harvest of microalgae biomass, which has gained extensive attention. There have been carried out massive studies in bacterial flocculation, many bacterial strains with flocculation activity were isolated and different types of bioflocculants were produced. However, harvest of algal biomass by bioflocculants which produced from actinomycete are deficiency. In this study, the bioflocculant from an actinomycete Streptomyces sp. hsn06 could be used to harvest Chlorella vulgaris biomass. Results Consecutive treatment with 20 mg·L − 1 bioflocculant and 5 mM CaCl 2 for 5 min showed the highest flocculating activity. The bioflocculant was a nonprotein substance with thermal stability and pH stability, which can be used in comprehensive applications. Chemical analysis of the bioflocculant indicated that it is a small molecule substance of moderate polarity with containing triple bond and cumulated double bonds. Algal temperature, pH, and metal ions showed great effects on the flocculation efficiency of the bioflocculant. Conclusions The bioflocculant produced by Streptomyces sp. hsn06 possesses the potential to harvest algal biomass with high-efficiency.

Background Prospective longitudinal studies have shown inconsistent effects of obesity phenotypes on the risk of cardiovascular disease (CVD) mortality. Also, longitudinal evidence from Chinese populations remained scarce. We aimed to investigate the association of obesity phenotypes assessed by body mass index (BMI) and metabolic syndrome (MetS) with risk of CVD mortality, leveraging the unique adiposity patterns and metabolic vulnerability of Asian populations. Methods A subset of 26,884 participants (aged 49.30 ± 10.37 years, 39.23% men) from Taizhou longitudinal study were followed up to 8 years. Obesity phenotypes were categorized into 4 groups including metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO) and metabolically unhealthy obese (MUO), using BMI categories from Chinese criteria (obesity: ≥28.0 kg/m²) and MetS defined by International Diabetes Federation (IDF) consensus. The death caused by CVD were identified based on international classification of diseases-10th Revision (ICD-10). Data were analyzed using the Cox regression models and Laplace regression models. Results Of 26,884 participants, 15,462 (57.5%), 1,702 (6.3%), 3,656 (13.6%) and 2,064 (7.7%) subjects were classified into the MHNO, MHO, MUNO and MUO group, respectively. At the end of the follow-up, 113 (0.39%) participants died because of CVD. Compared with the MHNO group, the hazards ratios (HRs) and 95% confidence intervals (CIs) of CVD mortality were 1.73 (1.03–2.91) and 1.97 (1.11–3.52) respectively in MUNO and MUO group. The multi-adjusted 50th percentile differences (50th PDs) (95% CIs) of time at incident CVD mortality in MUNO and MUO group were 0.97 (0.00-1.93) and 1.35 (0.31–2.39) years earlier respectively than those in MHNO group. MHO group showed no significant risk elevation (HR = 1.21, 0.68–2.17) despite the earlier 50th percentile differences of CVD mortality years (50th PD = 0.94, 95%CI: 0.38–2.25). Conclusions Metabolic abnormalities increased the risk of CVD mortality especially in participants with obesity.

High-efficiency propeller design is essential for reducing the total mass of near-space airships under low-Reynolds-number conditions. This study optimizes the overall design parameters of near-space airships by integrating an efficient engineering propeller design method based on characteristic blade elements. This overall configuration yields results close to those obtained from single-objective optimization of the propellers. Through analysis of the overall configuration, it is evident that there is limited room for optimization in terms of propeller efficiency improvement. Therefore, a variable-speed strategy that accounts for different flight speeds during day and night is proposed. The variable-speed strategy achieves a 29.6% reduction in total airship mass compared to the constant-speed baseline. These findings verify that optimizing flight speeds and propeller efficiency is effective for achieving lightweight airship designs.

The menstrual cycle is regulated by reproductive hormones such as estrogen which has been implicated in the pathogenesis of hypertension and is associated with obesity. However, to date there has scant study of hypertension in relation to menstrual characteristics and abnormalities. We hypothesize that adverse menstrual characteristics are associated with an increase the prevalence of hypertension and that this relationship is exacerbated by obesity. Our study leverages 178,205 healthy female participants (mean age = 29) in a population-based cross-sectional study in Tianjin, China. Menstrual characteristics including menstrual cycle length and regularity, menstrual bleeding length, menstrual blood loss and dysmenorrhea were assessed by self-reported questionnaires, and hypertension was diagnosed by physician. Multiple logistic regression models were used to assess the relationships between menstrual characteristics and hypertension. Normal length menstrual cycle (OR = 1.21, 95% CI: 1.03-1.41), oligomenorrhea (OR = 1.54, 95% CI: 1.12-2.07), irregular cycle (OR = 1.54, 95% CI: 1.22-1.93), and light menstrual blood loss (OR = 1.36, 95% CI: 1.06-1.72) were associated with hypertension among women who are overweight or obese, but not among women who are normal weight. Longer menstrual bleeding duration (OR = 1.44, 95% CI: 1.24-1.67) and dysmenorrhea were associated with increased prevalence of hypertension (OR = 1.20, 95% CI: 1.14-1.41) in all young women. The prevalence of hypertension is higher among women with menstrual abnormalities, and this association is modified by overweight and obesity.

ObjectivesTo examine the association between low birth weight (LBW) and cardiometabolic diseases (CMDs, including heart disease, stroke and type 2 diabetes mellitus) in adulthood, and to explore whether genetic, early-life environmental and healthy lifestyle factors play a role in this association.DesignA population-based twin study.SettingTwins from the Swedish Twin Registry who were born in 1958 or earlier participated in the Screening Across the Lifespan Twin (SALT) study for a full-scale screening during 1998–2002 and were followed up until 2014.Participants19 779 twin individuals in Sweden with birthweight data available (mean age: 55.45 years).Primary and secondary outcome measuresCMDs were assessed based on self-reported medical records, medication use and records from the National Patient Registry. A lifestyle index encompassing smoking status, alcohol consumption, exercise levels and Body Mass Index was derived from the SALT survey and categorised as unfavourable, intermediate or favourable. Data were analysed using generalised estimating equation (GEE) models and conditional logistic regression models.ResultsOf all participants, 3998 (20.2%) had LBW and 5335 (27.0%) had incident CMDs (mean age at onset: 63.64±13.26 years). In GEE models, the OR of any CMD was 1.39 (95% CI 1.27 to 1.52) for LBW. In conditional logistic regression models, the LBW–CMD association became non-significant (OR=1.21, 95% CI 0.94 to 1.56). The difference in ORs from the two models was statistically significant (p<0.001). In the joint effect analysis, the multiadjusted OR of CMDs was 3.47 (95% CI 2.72 to 4.43) for participants with LBW plus an unfavourable lifestyle and 1.25 (95% CI 0.96 to 1.62) for those with LBW plus a favourable lifestyle.ConclusionLBW is associated with an increased risk of adult CMDs, and genetic and early-life environmental factors may account for this association. However, a favourable lifestyle profile may modify this risk.

Maternal sevoflurane exposure during pregnancy is associated with increased risk for behavioral deficits in offspring. Several studies indicated that neurogenesis abnormality may be responsible for the sevoflurane-induced neurotoxicity, but the concrete impact of sevoflurane on fetal brain development remains poorly understood. We aimed to investigate whether maternal sevoflurane exposure caused learning and memory impairment in offspring through inducing abnormal development of the fetal prefrontal cortex (PFC). Pregnant mice at gestational day 15.5 received 2.5% sevoflurane for 6 h. Learning function of the offspring was evaluated with the Morris water maze test at postnatal day 30. Brain tissues of fetal mice were subjected to immunofluorescence staining to assess differentiation, proliferation, and cell cycle dynamics of the fetal PFC. We found that maternal sevoflurane anesthesia impaired learning ability in offspring through inhibiting deep-layer immature neuron output and neuronal progenitor replication. With the assessment of cell cycle dynamics, we established that these effects were mediated through cell cycle arrest in neural progenitors. Our research has provided insights into the cell cycle-related mechanisms by which maternal sevoflurane exposure can induce neurodevelopmental abnormalities and learning dysfunction and appeals people to consider the neurotoxicity of anesthetics when considering the benefits and risks of nonobstetric surgical procedures.

HIV-infected individuals are susceptible to Mycobacterium tuberculosis ( M.tb ) infection and are at high risk of developing active tuberculosis (TB). Interferon-gamma release assays (IGRAs) are auxiliary tools in the diagnosis of TB. However, the performance of IGRAs in HIV-infected individuals is suboptimal, which limits clinical application. Interferon-inducible protein 10 (IP-10) is an alternative biomarker for identifying M.tb infection due to its high expression after stimulation with M.tb antigens. However, whether IP-10 mRNA constitutes a target for the diagnosis of TB in HIV-infected individuals is unknown. Thus, we prospectively enrolled HIV-infected patients with suspected active TB from five hospitals between May 2021 and May 2022, and performed the IGRA test (QFT-GIT) alongside the IP-10 mRNA release assay on peripheral blood. Of the 216 participants, 152 TB patients and 48 non-TB patients with a conclusive diagnosis were included in the final analysis. The number of indeterminate results of IP-10 mRNA release assay (13/200, 6.5%) was significantly lower than that of the QFT-GIT test (42/200, 21.0%) ( P = 0.000026). IP-10 mRNA release assay had a sensitivity of 65.3% (95%CI 55.9% – 73.8%) and a specificity of 74.2% (95%CI 55.4% – 88.1%), respectively; while the QFT-GIT test had a sensitivity of 43.2% (95%CI 34.1% – 52.7%) and a specificity of 87.1% (95%CI 70.2% – 96.4%), respectively. The sensitivity of the IP-10 mRNA release assay was significantly higher than that of QFT-GIT test ( P = 0.00062), while no significant difference was detected between the specificities of these two tests ( P = 0.198). The IP-10 mRNA release assay showed a lower dependence on CD4 + T cells than that of QFT-GIT test. This was evidenced by the fact that the QFT-GIT test had a higher number of indeterminate results and a lower sensitivity when the CD4 + T cells counts were decreased ( P < 0.05), while no significant difference in the number of indeterminate results and sensitivity were observed for the IP-10 mRNA release assay among HIV-infected individuals with varied CD4 + T cells counts ( P > 0.05). Therefore, our study suggested that M.tb specific IP-10 mRNA is a better biomarker for diagnosis of TB in HIV-infected individuals.

This study aimed to investigate the association of the cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) with the trajectories of motor function over time and to assess the mediating effects of cardiovascular diseases (CVDs) accumulation and cognitive decline in such association. In Rush Memory and Aging Project, a total of 1,378 physical health participants (mean age: 79.3 ± 7.3 years) were followed up for up to 22 years. FGCRS at baseline was assessed and categorized into tertiles (lowest, middle, and highest). Global motor function (including dexterity, gait, and hand strength) was assessed annually with 10 motor tests. CVDs (including stroke, congestive heart failure, and other heart diseases) were ascertained at baseline and follow-ups, and the number of CVDs accumulation over time was assessed. Global cognitive function was tested annually by 19 tests. Data were analyzed using the linear mixed-effects models and mediation analysis. At baseline, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Over the follow-up (median: 5.3 years; interquartile range: 2.9-9.0 years), in multi-adjusted mixed-effects models, the highest FGCRS was associated with faster decline in global motor function (β = -0.0038; 95% confidence interval [CI]: -0.0069 to -0.0008), dexterity (β = -0.0056; 95% CI: -0.0093 to -0.0020), gait (β = -0.0039; 95% CI: -0.0077 to -0.0001), and hand strength (β = -0.0053; 95% CI: -0.0098 to -0.0008) compared with the lowest tertile. In mediation analysis, CVDs accumulation and cognitive decline mediated 8.4% and 42.9% of the association between FGCRS and global motor function over time, respectively. Higher cardiovascular risk burden is associated with a faster decline in motor function including dexterity, gait, and hand strength. CVDs accumulation and cognitive decline may partially mediate the association between cardiovascular risk burden and global motor function decline.