LncRNA-Snhg3 regulates mouse hepatic glycogenesis under normal chow diet.

Long noncoding RNAs (lncRNAs) are strongly associated with glucose homeostasis, but their roles remain largely unknown. In this study, the potential role of lncRNA-Snhg3 in glucose metabolism was evaluated both in vitro and in vivo. Here, we found a positive relationship between Snhg3 and hepatic glycogenesis. Glucose tolerance improved in hepatocyte-specific Snhg3 knock-in (Snhg3-HKI) mice, while it worsened in hepatocyte-specific Snhg3 knockout (Snhg3-HKO) mice. Furthermore, hepatic glycogenesis had shown remarkable increase in Snhg3-HKI mice and reduction in Snhg3-HKO mice, respectively. Mechanistically, Snhg3 increased mRNA and protein expression levels of PPP1R3B through inducing chromatin remodeling and promoting the phosphorylation of protein kinase B. Collectively, these results suggested that lncRNA-Snhg3 plays a critical role in hepatic glycogenesis.

Blood Profiles of Community-Dwelling People with Sarcopenia: Analysis Based on the China Health and Retirement Longitudinal Study.

INTRODUCTION: Routine blood factors can be economical and easily accessible candidates for sarcopenia screening and monitoring. The associations between sarcopenia and routine blood factors remain unclear. This study aimed to examine sarcopenia and blood factor associations based on a nation-wide cohort in China. METHODS: A total of 1,307 participants and 17 routine blood indices were selected from two waves (year 2011 and year 2015) of the China Health and Retirement Longitudinal Study (CHARLS). The diagnosis of sarcopenia was based on the criteria proposed by the Asian Working Group for Sarcopenia (AWGS 2019). Generalized mixed-effects models were performed for association analyses. A logistic regression (LR) model was conducted to examine the predictive power of identifying significant blood factors for sarcopenia. RESULTS: A higher sarcopenia risk was cross-sectionally associated with elevated blood concentrations of high-sensitivity C-reactive protein (hsCRP) (OR = 1.030, 95% CI [1.007, 1.053]), glycated hemoglobin (HbA1c) (OR = 1.407, 95% CI [1.126, 1.758]) and blood urea nitrogen (BUN) (OR = 1.044, 95% CI [1.002, 1.089]), and a decreased level of glucose (OR = 0.988, 95% CI [0.979, 0.997]). A higher baseline hsCRP value (OR = 1.034, 95% CI [1.029, 1.039]) and a greater over time change in hsCRP within 4 years (OR = 1.034, 95% CI [1.029, 1.039]) were associated with a higher sarcopenia risk. A higher BUN baseline value was related to a decreased sarcopenia risk over time (OR = 0.981, 95% CI [0.976, 0.986]), while a greater over time changes in BUN (OR = 1.034, 95% CI [1.029, 1.040]) and a smaller over time change in glucose (OR = 0.992, 95% CI [0.984, 0.999]) within 4 years were also related to a higher sarcopenia risk. LR based on significant blood factors (i.e., hsCRP, HbA1c, BUN, and glucose), and sarcopenia status in year 2015 yielded an area under the curve of 0.859 (95% CI: 0.836-0.882). CONCLUSION: Routine blood factors involved in inflammation, protein metabolism, and glucose metabolism are significantly associated with sarcopenia. In clinical practice, plasma hsCRP, BUN, blood sugar levels, sex, age, marital status, height, and weight might be helpful for sarcopenia evaluation and monitoring.

Advances in extraction, utilization, and development of chitin/chitosan and its derivatives from shrimp shell waste.

Shrimp consumption is in great demand among the seafood used globally. However, this expansion has resulted in the substantial generation and disposal of shrimp shell waste. Through literature search, it has been observed that since 2020, global scholars have shown unprecedented interest in shrimp shell waste and its chitin/chitosan. However, these new insights lack corresponding and comprehensive summarization and analysis. Therefore, this article provides a detailed review of the extraction methods, applications, and the latest research developments on chitin/chitosan from shrimp shells, including micro-nano derivatives, from 2020 to the present. The results indicate that chemical extraction remains the primary technique for the extraction and preparation of chitin/chitosan from shrimp shells. With further refinement and development, adjusting parameters in the chemical extraction process or employing auxiliary techniques such as microwave and radiation enable the customization of target products with different characteristics (e.g., deacetylation degree, molecular weight, and degree of acetylation) according to specific needs. Additionally, in pursuit of environmentally friendly, efficient, and gentle extraction processes, recent research has shifted toward microbial fermentation and green solvent methods for chitin/chitosan extraction. Beyond the traditional antibacterial, film-forming, and encapsulation functionalities, research into the applications of chitosan in biomedical, food processing, new materials, water treatment, and adsorption fields is gradually deepening. Chitin/chitosan derivatives and their modified products have also been a focal point of research in recent years. However, with the rapid expansion, the future development of chitin/chitosan and its derivatives still faces challenges related to the unclear mechanism of action and the complexities associated with industrial scale-up.

The role of adiponectin for immune cell function in metabolic diseases.

Adiponectin, as an indispensable regulator of the immune system, is the most abundant adipokine and is mainly produced by white adipose tissue. Adiponectin mediates the positive effects on systemic metabolism by regulating associated downstream signalling pathways; however, accumulating evidence shows that adiponectin plays an important role in regulating the function of innate and adaptive immune cells in the development of obesity and its related diseases. In this review, we focus on the biological function of adiponectin in regulating innate and adaptive immunity and outline the key role of adiponectin in various metabolic diseases, which will highlight a potential direction for adiponectin-based therapeutic interventions for metabolic diseases.

The impact of the Covid-19 pandemic on maternal delivery experiences and breastfeeding practices in China: data from a cross-sectional study.

BACKGROUND: The COVID-2019 pandemic has placed extensive pressure on health systems and posed a severe public health challenge worldwide. Lockdown measures implemented in many countries have delayed virus spread. However, a considerable number of people have faced unprecedented pressure, especially pregnant and breast-feeding women, because face-to-face professional support has been reduced during the lockdown in many countries. OBJECTIVES: To compare the delivery and infant feeding experiences of women who delivered before (BL) versus during (DL) the Covid-19 pandemic in Beijing, China and to investigate predictors of breastfeeding at 6-months. METHODS: Women aged ≥18 years with an infant ≤18 months of age completed an anonymous survey. Information/links were shared online and via local clinics in Beijing. Logistic regression was performed to assess predictors of breastfeeding during the first 6-months. RESULTS: One thousand eight hundred seven women provided data; BL 1231 (68.1%), DL 576 (31.9%). Significantly more mothers in DL group reported the lockdown had moderate to high impact to their household income (p = 0.013) and the convenience of purchasing daily necessities(p = 0.014). Compared to BL mothers, significantly more mothers in the DL groups thought their birth location and breastfeeding intention had been effected by the COVID-19 (p < 0.001, p = 0.036 respectively). Mostly breastfeeding (MBF, mainly breastfeeding with few non-formula fluids added) at 6 months was predicted by delivery during the lockdown period (OR1.43, 95% confidence interval (CI) 1.08, 1.90), younger maternal age (OR 0.96, 95%CI 0.93, 0.99), getting support from friends or relatives (OR 1.95, 95%CI 1.06, 3.59), and discussing health issues in online groups > four times a week (OR 1.66, 95%CI 1.09, 2.53). CONCLUSION: The COVID-19 pandemic and lockdown measures influenced mothers' planned birth location and breastfeeding intention. However, breastfeeding practice was maintained during the pandemic. Our results highlight the importance of feeding support as well as potential beneficial effects of increased mother-infant contact during the lockdown period which is relevant even under normal circumstances.

Causal Effect of Honorary Titles on Physicians' Service Volumes in Online Health Communities: Retrospective Study.

BACKGROUND: An OHC online health community (OHC) is an interactive platform for virtual communication between patients and physicians. Patients can typically search, seek, and share their experience and rate physicians, who may be involved in giving advice. Some OHC providers provide incentives in form of honorary titles to encourage the web-based involvement of physicians, but it is unclear whether the award of honorary titles has an impact on their consultation volume in an OHC. OBJECTIVE: This study is designed to identify the differential treatment effect of the incentive policy on the service volumes for the subgroups of treatment and control in an OHC. This study aims to answer the following questions: Does an honorary title for physicians impact their service volumes in an OHC? During the period of discontinuity, can we identify the sharp effect of the incentive award on the outcomes of physicians' service volumes? METHODS: We acquired the targeted samples based on treatment, namely, physicians with an honorary title or not and outcomes measured before and after the award of the 2 subgroups. A regression discontinuity design was applied to investigate the impact of the honorary titles incentive as a treatment in an OHC. There was a sharply discontinuous effect of treatment on physicians' online health service performance. The experimental data set consisted of 346 physicians in the treatment group (with honorary titles). Applying the propensity score matching method, the same size of physicians (n=346) was matched and selected as the control group. RESULTS: A sharp discontinuity was found at the time of the physician receiving the honorary title. The results showed that the parametric estimates of the coefficient were significantly positively (P<.001) associated with monthly home page views. The jump in the monthly volumes of home page views was much sharper than that of the monthly consultations. CONCLUSIONS: The changes in the volumes of monthly consultations and home page views reflect the differential treatment effect of honorary titles on physicians' service volumes. The effect of the incentive policy with honorary titles is objectively estimated from both the perspective of online and offline medical services in an OHC. Being named with honorary titles significantly multiplied monthly home page views, yet it did not significantly impact monthly consultations. This may be because consultation capacity is limited by the physician's schedule for consultations.

Yishenhuoxue formula regulates TGF-ß/Smad signal transduction to protect rats against Diabetic kidney disease injury.

TGF-ß signal pathway activation is vital in the pathogenesis of DKD. We aim to investigate the role of Yishenhuoxue formula on TGF-ß/Smad signal transduction in DKD rats. 60 male adult Wistar rats were enrolled and randomly allocated into four groups: N group, M group (given STZ 60mg/kg, ip), H group (given Yishenhuoxue formula 1.0g/kg/day, ig) and L group (given Yishenhuoxue formula 0.5g/kg/day, ig). The levels of BW, 24h UV, SCr, UCr, mALB were measured after 8 weeks treatment, while the levels of KW/BW index, CCr and UAER were calculated by relevant formula. The rats' left kidneys were harvested to detect histological changes by PAS staining and right kidneys were harvested to detect the levels of TGF-ß, Smad2/3, phosphorylated Smad 2/3, Smad 7 and CTGF by western blot analysis. We found that Yishenhuoxue formula treatment can protect kidneys from DKD injury, which is illustrated with following criteria: 1) a significant decrement in KW/BW index, 24h UV, SCr, mALB and UAER, while a significant increment in BW, UCr, CCr (p<0.05 vs. M group); 2) minor and segmental changes as slight expansion of the glomerular basement membrane compared with M group; 3) an apparent decrease in levels of TGF-ß1, phosphorylated Smad 2/3 and CTGF, while an apparent increase in levels of Smad 2/3 and Smad7 compared with M group (p<0.05). The studies confirm that Yishenhuoxue formula has strong inhibitory effect on TGF-ß/Smad signal transduction in DKD rats' kidneys by decreasing expression of TGF-ß1, weakening of Smad 2/3 phosphorylation and increasing expression of Smad 7.

The association between apolipoprotein E and gallstone disease: an updated meta-analysis.

BACKGROUND: Gallstone disease (GSD) is a common biliary tract disease worldwide. Previous studies have investigated the association of apolipoprotein E (APOE) E4 with GSD and reported inconsistent results. METHODS: In this paper, we conducted meta-analyses to examine whether APOE E4 is associated with the risk of GSD. A systematic literature search was performed in PubMed, Cochrane Library, EMBASE, and Google Scholar using the following inclusion criteria: 1) Studies on human subjects; 2) subjects in the control group must undergo ultrasound GSD screening, and presence of GSD in the experiment group can be clearly determined, e.g., diagnosis of GSD through ultrasound screening or a previous history of cholecystectomy or cholelithiasis; 3) the studies reported APOE genotype data (APOE E4+ vs. E4-) for subjects with and without GSD. In all the meta-analyses, we used random-effects models to calculate the odds ratios (ORs) as a measure of association as well as the corresponding confidence intervals (CIs). RESULTS: Our literature search found 13 publications with 14 studies, including a total of 1632 GSD patients and 5001 controls, that met the eligibility criteria and were included in the meta-analyses. We did not find a significant association between APOE E4 and risk of GSD (OR = 1.23, 95% CI: 0.89-1.68; p = 0.205). No significant associations were observed in subgroup analyses by gender and mean age. We obtained similar insignificant findings if an additive model was used, if subjects who had E2E4 genotype were excluded, or if low-quality studies were excluded. CONCLUSION: Our meta-analysis found insufficient evidence for the effect of APOE E4 on GSD risk. Future studies with large sample sizes that control for important confounding/risk factors are needed to validate our findings and to explore other genetic loci that might affect GSD risk.

Protocol registration or development may benefit the design, conduct and reporting of dose-response meta-analysis: empirical evidence from a literature survey.

BACKGROUND: To investigate the prevalence of protocol registration (or development) among published dose-response meta-analyses (DRMAs), and whether DRMAs with a protocol are better than those not. METHODS: Three databases were searched for eligible DRMAs. The modified AMSTAR (14 items) and PRISMA checklists (26 items) were used to assess the methodological and reporting quality, with each item assigned 1 point if it met the requirement or 0 if not. We matched (1,2) DRMAs with registered or published protocol to those not, by region and publication years. The summarized quality score and compliance rate of each item were compared between the two groups. Multivariable regression was employed to see if protocol registration or development was associated with total quality score. RESULTS: We included 529 DRMAs, with 45 (8.51%) completed protocol registration or development. We observed a higher methodological score for DRMAs with protocol than the matched controls (9.47 versus 8.58, P <  0.01); this embodied in 4 out of 14 items of AMSTAR [e.g., Duplicate data extraction (rate difference, RD = 0.17, 95% CI: 0.04, 0.30; P = 0.01). A higher reporting score (cubic transformed) for DRMAs with protocol than the matched controls was also observed (11,875.00 versus 10,229.53, P <  0.01); which embodied in 6 out of 26 items of PRISMA [e.g. Describe methods for publication bias (RD = 0.08, 95% CI: 0.01, 0.14; P = 0.02)]. Regression analysis suggested positive association between protocol registration or development and total reporting score (P = 0.012) while not for methodological score (P = 0.87). CONCLUSIONS: Only a small proportion of DRMAs completed protocol registration or development, and those with protocol were better reported than those not. Protocol registration or development is highly desirable.

Evaluation of salinomycin isolated from Streptomyces albus JSY-2 against the ciliate, Ichthyophthirius multifiliis.

The present study was undertaken to investigate the antiparasitic activity of extracellular products of Streptomyces albus. Bioactivity-guided isolation of chloroform extracts affording a compound showing potent activity. The structure of the compound was elucidated as salinomycin (SAL) by EI-MS, 1H NMR and 13C NMR. In vitro test showed that SAL has potent anti-parasitic efficacy against theronts of Ichthyophthirius multifiliis with 10 min, 1, 2, 3 and 4 h (effective concentration) EC50 (95% confidence intervals) of 2.12 (2.22-2.02), 1.93 (1.98-1.88), 1.42 (1.47-1.37), 1.35 (1.41-1.31) and 1.11 (1.21-1.01) mg L-1. In vitro antiparasitic assays revealed that SAL could be 100% effective against I. multifiliis encysted tomonts at a concentration of 8.0 mg L-1. In vivo test demonstrated that the number of I. multifiliis trophonts on Erythroculter ilishaeformis treated with SAL was markedly lower than that of control group at 10 days after exposed to theronts (P < 0.05). In the control group, 80% mortality was observed owing to heavy I. multifiliis infection at 10 days. On the other hand, only 30.0% mortality was recorded in the group treated with 8.0 mg L-1 SAL. The median lethal dose (LD50) of SAL for E. ilishaeformis was 32.9 mg L-1.

Spermidine ameliorates non-alcoholic fatty liver disease through regulating lipid metabolism via AMPK.

In this study, treatment of high-fat diet-induced obesity (DIO) C57BL/6J mice with spermidine decreased body weight and subcutaneous and visceral fat content, reversed the apparent hepatosteatosis, and reduced hepatic intracellular and serum triglyceride and total cholesterol concentrations. Moreover, spermidine treatment improved glucose tolerance and insulin sensitivity in DIO mice. The mechanism studies indicated that spermidine indeed increased the phosphorylation of hepatic AMP-activated protein kinase (AMPK), and inhibited the expression of lipogenic genes in vivo and in vitro. Moreover, these spermidine-mediated molecular effects were also abolished by compound C, an inhibitor of AMPK, in primary hepatocytes. In summary, spermidine protected against DIO-induced hepatosteatosis by decreasing lipogenic genes expression through an AMPK-mediated mechanism.

The time trends of cognitive impairment incidence among older Chinese people in the community: based on the CLHLS cohorts from 1998 to 2014.

Objective: to examine a 16-year trend in cognitive impairment (CI) incidence and associated factors among older Chinese people. Subjects: aged 60 and above whose cognitive function were normal at their first test. Methods: a secondary analysis that identified subjects from the database of Chinese Longitudinal Healthy Longevity Survey (CLHLS). The database contained mixed longitudinal cohorts of older Chinese people surveyed in 1998, 2000, 2002, 2005, 2008-09, 2011-12 and 2014. The cognitive function of subjects was tested using the Chinese Mini-Mental State Examination (CMMSE) in each wave. The unique individual code identified a mixed cohort of 17,896 subjects who had multiple CMMSE measures over a 16-year period and available covariates for the analysis. CI was defined as the CMMSE score below 18 points. Crude and age-standardised incidence of CI by gender were calculated by year of survey. Risk factor adjusted time trends in the incidence were examined using multilevel regression models. Results: age-standardised CI incidence decreased from 58.77‰ to 10.09‰ (P < 0.001) from 1998 to 2014, and this decrease remained after adjusting for covariates. About 15.8% in the observed decline was explained by higher education, and 7.9% was due to health practice (regular exercise, physical activity and cognitive activity), beyond age and gender effects. Conclusion: the CI incidence among older Chinese people decreased from 1998 to 2014. Lower education level and less frequent health practices mentioned above were important risk factors in CI prevention.

[Clinical analysis of cervus and cucumis polypeptide injection for lumbar vertebrae diseases based on real world hospital information system].

To analyze the clinical drug use characteristics and medication rules of cervus and cucumis polypeptide injection (CCP injection) for the patients with lumbar vertebra diseases. Based on the electronic medical data of 6 990 patients with CCP injection for lumbar vertebra diseases from 25 first-class hospitals over the whole country from 2004, statistical analysis was conducted for their general information, diagnostic information, orders information, laboratory test information and treatment results. The results showed that the age distribution was highest in patients aged 45 to 64 (3 883, 55.55%); protrusion of lumbar intervertebral disc was most common among lumbar vertebra diseases (5 519, 82.50%); and TCM syndrome mainly included hemostasis. The daily dose was most between 8-12 mL, with a usual treatment course of 1-3 d. Commonly used western medicines in combined drug use included hypertonic dehydrating agent, antibiotics and nutrition nerve medicines, and the commonly used traditional Chinese medicines in combined drug use included the drugs with promoting blood circulation to remove blood stasis, kidney-tonifying and bone-building agents, and formula for clearing heat and removing toxicity, etc. The most commonly used western medicines are methylamine, adenosine, lidocaine injection, mannitol, et al, and the most commonly used Chinese medicines included Jintiange capsules, Qianggu capsules, et al. It is suggested that CCP injection for lumbar vertebrae diseases is mainly used in middle-aged and elderly patients, and is frequently used in combination with kidney-tonifying and bone-building agents, drugs with promoting blood circulation to remove blood stasis, analgesic agents and antibiotics.

[Intranasal absorption of rivastigmine hydrogen tartrate and brain targeting evaluation].

To investigate factors influencing the intranasal absorption of rivastigmine hydrogen tartrate (RHT), we studied the pharmacokinetics of RHT after intranasal administration and evaluated its brain targeting behavior. In situ rat nasal perfusion model was used in the study and pH impact was examined on the intranasal absorption of RHT. High performance liquid chromatography (HPLC) method was established to measure RHT concentration in the plasma and brain tissue after intranasal and intravenous administration. The pharmacokinetic parameters, drug targeting index(DTI), and nose-to-brain direct transport percentage (DTP) were calculated. It was demonstrated that the intranasal absorption mechanism of RHT was passive diffusion. The absorption rate was highest at pH 6.0. The absolute bioavailability of intranasally administrated RHT was 73.58%. Compared with that of intravenous administration, RHT absorption into the brain was faster and more efficient after intranasal delivery, and the DTI value was 195.27% of intravenous injection. Moreover, 48.79% of the drug can be absorbed directly from the nose into the brain without systematic circulation. Meanwhile, drug elimination half-time in the brain was prolonged by 1.4 fold compared to that of intravenous injection. In conclusion, intranasal administration of RHT not only improves drug absorption into the system, but also enhances drug absorption rate and content in the brain remarkably, which is an advantage in the treatment of central nervous system-related diseases.

[Optimization and in vitro characterization of resveratrol-loaded poloxamer 403/407 mixed micelles].

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.

[Factors and validity analysis of Mini-Mental State Examination in Chinese elderly people].

OBJECTIVE: To examine factors that may have impact on the Mini-Mental State Examination (MMSE) screening validity, which could lead to further establishing the general model of the MMSE score in Chinese health elderly and to improve the screening accuracy of the existing MMSE reference. METHODS: Based on the data of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), the MMSE scores of 19,117 normal elderly and 137 dementia patients who met the inclusion criteria were used for the analysis. The area under the curve (AUC) and validity indexes were used to compare the screening accuracy of various criteria. Multiple linear regression was used to identify factors that had impact on the MMSE score for both the normal and dementia elderly. Descriptive analysis was performed for differences in the MMSE scores by age trends and gender between the normal and dementia elderly. RESULTS: The AUC of MMSE was ≥0.75(P<0.05). The MMSE score of the normal elderly declined nonlinearly as the age grew older(male: R2=0.924, P<0.05; female: R2=0.951, P<0.05), and increased nonlinearly as the education level rose(male: R2=0.948, P<0.05; female: R2=0.859, P< 0.05). The females had significantly lower MMSE scores than the males, with a faster decline trend with age than the males (95%CI of female partial regression coefficient was not overlapped with 95%CI of male partial regression coefficient). The dementia elderly showed a much lower MMSE score (male: difference of Z score:-1.573, P<0.05; female: difference of Z score:-1.222, P<0.05) and tended to with a faster decline speed than that of the normal elderly (95%CI of dementia partial regression coefficient included 95%CI of normal partial regression coefficient). CONCLUSION: The screening validity of MMSE in CLHLS is not affected by educational level. The analysis of factors that may impact on the MMSE screening validity are gender, age, vision and residence which with validity identification. These four factors can be used as assist tool of MMSE in the screening of dementia to improve the screening accuracy.

Beneficial effect of sequential treatment with high-dose steroids and short-course oral glucocorticoids in patients with severe influenza virus-associated pneumonia.

Accumulating evidence supports that glucocorticoid treatment for viral pneumonia (VPA) can shorten the disease course and improve survival. However, currently, the use of glucocorticoids in treating VPA remains controversial. Moreover, a unified standard for the dosage and duration of glucocorticoid therapy has not been presented in published articles. A retrospective analysis was conducted in patients who were hospitalized for severe influenza virus-associated pneumonia, and they received sequential treatment with high-dose glucocorticoids and short-course oral glucocorticoids. Patients were followed up for 3 months. A total of 11 patients were included in the study (average age 56 years). There was no gender difference, but age and underlying diseases could be risk factors for severe influenza virus-associated pneumonia. The types of viruses causing pneumonia included influenza A/B. The main clinical symptoms of patients were fever, cough, sputum production, and dyspnea. Chest computed tomography showed multiple ground-glass shadows in the lobes, and the presence of bacterial and fungal infections was accompanied by consolidation shadows. After glucocorticoid therapy, the symptoms improved. None of the patients underwent tracheal intubation, and all survived. After a 3-month follow-up, lung CT absorption in all patients had reached more than 80%, and lung imaging absorption in 20% patients was complete. No serious complications occurred in any of the patients. Sequential treatment with high-dose steroids and short-course oral glucocorticoids may be helpful for reducing the tracheal intubation rate and mortality rate in patients with severe influenza virus-associated pneumonia. Additionally, short-course oral glucocorticoids may reduce pulmonary fibrosis in patients with severe influenza virus-associated pneumonia without any serious complications.

Parameter-Efficient Fine-Tuning Enhances Adaptation of Single Cell Large Language Model for Cell Type Identification.

Single-cell sequencing transformed biology and medicine, providing an unprecedented high-resolution view at the cellular level. However, the vast variability inherent in single-cell sequencing data impedes its utility for in-depth downstream analysis. Inspired by the foundation models in natural language processing, recent advancements have led to the development of single-cell Large Language Models (scLLMs). These models are designed to discern universal patterns across diverse single-cell datasets, thereby enhancing the signal-to-noise ratio. Despite their potential, multiple studies indicate existing scLLMs do not perform well in zero-short settings, highlighting a pressing need for more effective adaptation techniques. This research proposes several adaptation techniques for scLLMs by preserving the original model parameters while selectively updating newly introduced tensors. This approach aims to overcome the limitations associated with traditional fine-tuning practices, such as catastrophic forgetting and computational inefficiencies. We introduce two Parameter-Efficient Fine-Tuning (PEFT) strategies specifically tailored to refine scLLMs for cell type identification. Our investigations utilizing scGPT demonstrate that PEFT can enhance performance, with the added benefit of up to a 90% reduction in parameter training compared to conventional fine-tuning methodologies. This work paves the way for a new direction in leveraging single-cell models with greater efficiency and efficacy in single-cell biology.

Dynamic selection of high-affinity aptamers using a magnetically activated continuous deflection microfluidic chip.

To accelerate the discovery of high-affinity aptamers, a magnetically activated continuous deflection (MACD) chip was designed. The MACD chip could achieve dynamic selection in a continuous flow, which meant that the binding and separation were carried out consecutively. Dynamic selection could make selection efficient. Low-affinity sequences could be eluted in time and high-affinity sequences could be enriched via dynamic selection. The stringency of the conditions could be further increased by lowering the target concentration in the dynamic selection. Finally, a C.al3 aptamer with high-affinity and high-specificity for Candida albicans (C. albicans) was obtained through six rounds of selection. Its dissociation constant (Kd) was 7.9 nM. This demonstrated that dynamic selection using a MACD chip was an effective method for high-affinity aptamer selection.

LncRNA Snhg3 aggravates hepatic steatosis via PPARγ signaling.

LncRNAs are involved in modulating the individual risk and the severity of progression in metabolic dysfunction-associated fatty liver disease (MASLD), but their precise roles remain largely unknown. This study aimed to investigate the role of lncRNA Snhg3 in the development and progression of MASLD, along with the underlying mechanisms. The result showed that Snhg3 was significantly downregulated in the liver of high-fat diet-induced obesity (DIO) mice. Notably, palmitic acid promoted the expression of Snhg3 and overexpression of Snhg3 increased lipid accumulation in primary hepatocytes. Furthermore, hepatocyte-specific Snhg3 deficiency decreased body and liver weight, alleviated hepatic steatosis and promoted hepatic fatty acid metabolism in DIO mice, whereas overexpression induced the opposite effect. Mechanistically, Snhg3 promoted the expression, stability and nuclear localization of SND1 protein via interacting with SND1, thereby inducing K63-linked ubiquitination modification of SND1. Moreover, Snhg3 decreased the H3K27me3 level and induced SND1-mediated chromatin loose remodeling, thus reducing H3K27me3 enrichment at the Pparg promoter and enhancing PPARγ expression. The administration of PPARγ antagonist T0070907 improved Snhg3-aggravated hepatic steatosis. Our study revealed a new signaling pathway, Snhg3/SND1/H3K27me3/PPARγ, responsible for mice MASLD and indicates that lncRNA-mediated epigenetic modification has a crucial role in the pathology of MASLD.