Targeted regulation of autophagy using sorafenib-loaded biomineralization nanoenzyme for enhanced photodynamic therapy of hepatoma.

Sorafenib (SF), a multi-targeted tyrosine kinase inhibitor, serves as a primary therapeutic modality for advanced liver cancer. Nonetheless, its clinical efficacy is hindered by various obstacles, such as limited bioavailability and inadequate accumulation. This study introduces a novel biomimetic mineralization enzyme, known as BSA@Pt/Ce6/SF@M (PCFM). The PCFM incorporates platinum (Pt) as a catalytic agent, SF as a molecular-targeted therapeutic agent, and Ce6 as a photosensitizer within liver cancer cell membranes. This strategy enables the combination of various anti-tumor treatments, such as photodynamic therapy (PDT) and autophagy induction, leading to increased bioavailability of SF and achieving a multidimensional synergistic anticancer effect. The PDT effect produced by Ce6 in PCFM greatly enhances SF-induced autophagy, effectively promoting autophagic cell death. Furthermore, Pt dissociates from the biomineralization process, acquiring peroxidase properties through chemokinetic reactions. This facilitates the catalysis of significant oxygen generation, addressing the challenge of hypoxia in the tumor microenvironment and improving the efficacy of PDT. Moreover, the SF further enhances therapeutic efficacy by inducing autophagy in response to energy deprivation, as indicated by the reduced levels of HIF-1α, p62, along with increased levels of ROS and LC3-Ⅱ/Ι. This biomineralization-based nanoenzyme exhibits strong anti-tumor characteristics, offering a novel strategy for overcoming challenges in liver cancer treatment.

The Interplay between nighttime/midday sleep duration and the number of new-onset chronic diseases: A decade-long prospective study in China.

OBJECTIVE: To investigate the interplay between individual nighttime and midday sleep duration and the number of new-onset chronic diseases and determine the optimal sleep duration associated with lowest number of new-onset chronic diseases. METHODS: We used data from the China Health and Retirement Longitudinal Study (CHARLS) covering a decade and involving 10,828 participants. A random intercept cross-lagged model was used to explore the interplay between nighttime/midday sleep durations and new-onset chronic diseases at both the within-individual and between-individual levels, followed by a dose-response analysis at the between-individual level to determine the optimal sleep duration. New-onset chronic diseases include 14 types of self-reported diseases diagnosed by doctors. RESULTS: Within-individual analysis revealed that increased nighttime/midday sleep duration led to a higher number of new-onset chronic diseases, and an increased number of new-onset chronic diseases resulted in decreased nighttime sleep duration. Between nighttime and midday sleep, one type of sleep duration increase was likely to lead to an increase in another type. Between-individual analysis found a nonlinear relationship between the number of new-onset chronic diseases and nighttime sleep duration, identifying the optimal nighttime sleep duration as 7.46 h. CONCLUSIONS: These findings elucidate the interplay between sleep duration and number of new-onset chronic diseases and underscore the need for public awareness and comprehensive interventions. Future studies should focus on refining sleep monitoring and exploring the sleep-chronic diseases nexus in greater depth.

Real-world effectiveness of influenza vaccine against medical-attended influenza infection during 2023/24 season in Ili Kazakh Autonomous Prefecture, China: A test-negative, case-control study.

In the post-COVID-19 pandemic era, influenza virus infections continuously lead to a global disease burden. Evaluating vaccine effectiveness against influenza infection is crucial to inform vaccine design and vaccination strategy. In this study, we recruited 1120 patients with influenza-like illness (ILI) who attended fever clinics of 4 sentinel hospitals in the Ili Kazakh Autonomous Prefecture, Xinjiang Uygur Autonomous Region, China, from January 1 to April 7, 2024. Using a test-negative design, we estimated influenza vaccine effectiveness (VE) of 54.7% (95% CrI: 23.7, 73.1) against medical-attended influenza infection, with 62.3% (95% CrI: 29.3, 79.8) against influenza A, and 51.2% (95% CrI: 28.7, 83.0) against influenza B. Despite the moderate VE estimated in this study, influenza vaccination remains the most important approach to prevent influenza at the community level.

Sequential dual-locking strategy using photoactivated Pt(IV)-based metallo-nano prodrug for enhanced chemotherapy and photodynamic efficacy by triggering ferroptosis and macrophage polarization.

Selective activation of Pt(IV) prodrugs within tumors has emerged as a promising strategy in tumor treatment. Although progress has been made with photo- and ultrasound-activated Pt(IV) prodrugs, concerns remain over the non-specific activation of photosensitizers (PS) and the potential for phototoxicity and chemical toxicity. In this study, a sequential dual-locked Pt(IV) nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed. The Pt(IV) prodrug was prepared by conjugating PS-locked Pt(IV) to a polymeric core, which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug. Under acidic tumor microenvironment conditions, the metallo-nano prodrug undergoes dissociation of iron, triggering a reduction process in oxaliplatin under light irradiation, resulting in the activation of both chemotherapy and photodynamic therapy (PDT). Additionally, the prodrug could induce metallo-triggered ferroptosis and polarization of tumor-associated macrophages (TAM), thereby enhancing tumor inhibition. The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs, making it a promising new direction in cancer treatment.

Mediation effect of sleep time on the association between outdoor activity and myopia in Chinese children and adolescents: a cross-sectional study.

BACKGROUND: This study aimed to assess the association between outdoor activity and myopia among children and adolescents and investigate whether sleep time could mediate this relationship. METHODS: This cross-sectional study was performed on students aged 4-16 years in China, from August 2021 to January 2022. Outdoor activity was assessed by the Assessment Questionnaire of Exposure to Sunlight Activities for Students (AQESAS). Binary logistic regression combined with the mediation analysis was used to analyze the association of AQESAS with myopia and the mediating effect of sleep time on this relationship. RESULTS: The prevalence of myopia was 53.51% (N = 1609). Multivariate logistic regression analysis showed that more sleep time (OR = 0.794, 95%CI: 0.707-0.893) and a higher score of AQESAS (OR = 0.989, 95%CI: 0.981-0.996) were significantly associated with a decreased risk of myopia. Mediation analysis revealed that sleep time plays a mediating role in the association between outdoor activity and myopia (ACME = -0.0006, P < 0.001), and the mediation proportion was 19.7%. CONCLUSION: Outdoor activity affects myopia directly and indirectly through sleep time. The result suggested that children may be able to reduce the risk of myopia by promoting sleep through increased awareness of outdoor activity and exposure to sunlight.

Effectiveness of azvudine against severe outcomes among hospitalized COVID-19 patients in Xinjiang, China: a single-center, retrospective, matched cohort study.

BACKGROUND: Since the end of 2022, Azvudine was widely used to treat hospitalized coronavirus disease 2019 (COVID-19) patients in China. However, data on the real-world effectiveness of Azvudine against severe outcomes and post-COVID-19-conditions (PCC) among patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants was limited. This study evaluates the effectiveness of Azvudine in hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominance period. METHODS: From 1 November 2022 to 1 July 2023, an SARS-CoV-2 Omicron BA.5 dominant period, we conducted a single-center retrospective cohort study based on hospitalized patients with laboratory-confirmed SARS-CoV-2 infection from a tertiary hospital in Shihezi, China. Patients treated with Azvudine and usual care were propensity-score matched (PSM) at a 1:1 ratio to a control group in which patients received usual care only, with matching based on covariates such as sex, age, ethnicity, number of preexisting conditions, antibiotic use at admission, and baseline complete blood cell count. The primary outcomes were all-cause death and short-term (60 days) PCC post discharge. The secondary outcomes included the initiation of invasive mechanical ventilation and PCC at long-term post discharge (120 days). Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) of Azvudine treatment for both all-cause death and invasive mechanical ventilation, and logistic regression models were used to estimate the odds ratios (OR) for short-term and long-term PCC. Subgroup analyses were performed based on a part of the matched covariates. RESULTS: A total of 2,639 hospitalized patients with SARS-CoV-2 infection were initially identified, and 2,069 ineligible subjects were excluded from analyses. After matching, 297 Azvudine recipients and 297 matched controls were eligible for analyses. The incidence rate of all-cause death was relatively lower in the Azvudine group than in control group (0.007 per person, 95% confidence interval [CI]: 0.001, 0.024 vs 0.128, 95% CI: 0.092, 0.171), and the use of Azvudine was associated with a significantly lower risk of death (HR: 0.049, 95% CI: 0.012, 0.205). Subgroup analyses suggested protection of Azvudine against the risks of all-cause death among men, age over 65, patients without the preexisting conditions, and patients with antibiotics dispensed at admission. Statistical differences were not observed between the Azvudine group and the control group for the risks of invasive mechanical ventilation or short and long-term PCC. CONCLUSIONS: Our findings indicated that Azvudine was associated with lower risk of all-cause death among hospitalized patients with Omicron BA.5 infection in a real-world setting. Further investigation is needed to explore the effectiveness of Azvudine against the PCC after discharge.

This study aims to evaluate the real-world effectiveness of Azvudine among hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominant epidemic phase. Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) for all-cause death. We found that the use of Azvudine was associated with a significantly reduced risk of all-cause death among hospitalized patients with SARS-CoV-2 infection.

Short stature with brachydactyly caused by a novel mutation in the IHH gene and response to 4-year growth hormone therapy: a case report.

Background: The etiology of short stature is heterogeneous. The disturbance of endochondral ossification and cartilage matrix synthesis caused by genetic mutations often causes short height combined with skeletal deformities in children. Some patients with minor skeletal abnormalities, such as short fingers and mild limb shortening, may be overlooked by clinicians and misdiagnosed as idiopathic short stature (ISS) or growth hormone deficiency (GHD). Case Description: We conducted a detailed investigation of laboratory and imaging examinations on a family with short stature and non-classical brachydactyly type A1 (BDA1) and summarized the clinical features. They received whole exome sequencing (WES) to reveal the possible genetic variation. A heterozygous mutation in the Indian hedgehog gene (IHH) (c.387_388insC, p.Thr130Hisfs*18) was found in the two siblings and their mother. The siblings both started recombinant human growth hormone (rhGH) therapy (rhGH: 33 µg/kg/day) and followed up for 4 years. After treatment, the siblings' height improved significantly, and they acquired a significant increase in the height standard deviation score (SDS) (the boy: +2.54, the girl: +1.86) during the 4-year therapy. No noticeable adverse effect was observed during rhGH treatment. Conclusions: We found a novel heterozygous pathogenic mutation in the IHH gene in a family and detailed the phenotype with short stature and non-classical BDA1. The therapy of rhGH showed promising effects. To avoid misdiagnosis, clinicians should not overlook minor skeletal anomalies in patients with short stature, especially those with a family history.

Association of past and current sleep duration with structural brain differences: A large population-based study from the UK Biobank.

OBJECTIVE: This study aimed to examine the association between past/current sleep duration and macro-/micro-structural brain outcomes and explore whether hypertension or social activity plays a role in such association. METHODS: Within the UK Biobank, 40 436 dementia-free participants (age 40-70 years) underwent a baseline assessment followed by a brain magnetic resonance imaging (MRI) scan 9 years later. Past (baseline) and current (MRI scans) sleep duration (hours/day) were recorded and classified as short (≤5), intermediate (6-8), and long (≥9). Brain structural volumes and diffusion markers were assessed by MRI scans. RESULTS: Compared with past intermediate sleep, past short sleep was related to smaller cortex volumes (standardized ß [95 % CI]: -0.04 [-0.07, -0.02]) and lower regional fractional anisotropy (FA) (-0.08 [-0.13, -0.03]), while past long sleep was related to smaller regional subcortical volumes (standardized ß: -0.04 to -0.07 for thalamus, accumbens, and hippocampus). Compared to current intermediate sleep, current short sleep was associated with smaller cortex volumes (-0.03 [-0.05, -0.01]), greater white matter hyperintensities (WMH) volumes (0.04 [0.01, 0.08]), and lower regional FA (-0.07 [-0.11, -0.02]). However, current long sleep was related to smaller total brain (-0.03 [-0.05, -0.02]), grey matter (-0.05 [-0.07, -0.03]), cortex (-0.05 [-0.07, -0.03]), regional subcortical volumes [standardized ß: -0.05 to -0.09 for putamen, thalamus, hippocampus, and accumbens]), greater WMH volumes (0.06 [0.03, 0.09]), as well as lower regional FA (-0.05 [-0.09, -0.02]). The association between current long sleep duration and poor brain health was stronger among people with hypertension or low frequency of social activity (all Pinteraction <0.05). CONCLUSIONS: Both past and current short/long sleep are associated with smaller brain volume and poorer white matter health in the brain, especially in individuals with hypertension and low frequency of social activity. Our findings highlight the need to maintain 6-8 h' sleep duration for healthy brain aging.

The Impact of Back Optic Zone Design in Orthokeratology on Visual Performance.

Purpose: To evaluate the visual performance in adolescents undergoing orthokeratology (OrthoK) treatment with two different optical zone diameters (OZDs). Methods: This randomized, double-masked, self-controlled prospective study was conducted at Tianjin Eye Hospital (Tianjin, China) in June 2022. Thirty-six eligible schoolchildren were enrolled and fitted with corneal refractive therapy lenses with two sizes of OZDs (5 mm [5OZ] and 6 mm [6OZ]). Each participant was randomized to wear the 5OZ in one eye and the 6OZ in the contralateral eye. Subjective visual quality was assessed using visual acuity, refraction, contrast sensitivity function, and visual symptoms, and the objective optical quality was assessed using ocular higher order aberrations (HOAs) and modulation transfer function (MTF). Results: Thirty-five myopic children completed a 1-month follow-up visit. The 5OZ lens induced significantly smaller treatment zone diameters than the 6OZ lens (P < 0.001). Subjective visual quality did not differ significantly between the two groups. Compared to baseline, aberrations of Z40, coma-like, spherical-like, and total HOAs in both groups increased significantly (P < 0.05). For the 3-mm pupils, spherical aberration in the 5OZ group was significantly higher than that in the 6OZ group (P < 0.05). The MTF value of the 6OZ group was significantly higher than that of 5OZ group for 0.3 and 1.5 cycles per degree for the 3-mm pupils (P = 0.006 and P = 0.026, respectively). However, HOAs or MTF did not differ significantly between the two groups for the 5-mm pupils. Conclusions: The difference induced by varying OZD was significant only in the smaller pupil condition. The selection of OZD in OrthoK designs in real-world patient management should be done while considering individual pupil size. Translational Relevance: This study revealed that the objective visual quality of small OZD lenses was only slightly affected for the small pupil size.

Estimating effects of whole grain consumption on type 2 diabetes, colorectal cancer and cardiovascular disease: a burden of proof study.

BACKGROUND: Previous studies on whole grain consumption had inconsistent findings and lacked quantitative assessments of evidence quality. Therefore, we aimed to summarize updated findings using the Burden of Proof analysis (BPRF) to investigate the relationship of whole grain consumption on type 2 diabetes (T2D), colorectal cancer (CRC), stroke, and ischemic heart disease (IHD). METHODS: We conducted a literature search in the Medline and Web of Science up to June 12, 2023, to identify related cohort studies and systematic reviews. The mean RR (relative risk) curve and uncertainty intervals (UIs), BPRF function, risk-outcome score (ROS), and the theoretical minimum risk exposure level (TMREL) were estimated to evaluate the level of four risk-outcome pairs. RESULTS: In total, 27 prospective cohorts were included in our analysis. Consuming whole grain at the range of TMREL (118.5-148.1 g per day) was associated with lower risks: T2D (declined by 37.3%, 95% UI: 5.8 to 59.5), CRC (declined by 17.3%, 6.5 to 27.7), stroke (declined by 21.8%, 7.3 to 35.1), and IHD (declined by 36.9%, 7.1 to 58.0). For all outcomes except stroke, we observed a non-linear, monotonic decrease as whole grain consumption increased; For stroke, it followed a J-shaped curve (the greatest decline in the risk of stroke at consuming 100 g whole grain for a day). The relationships between whole grain consumption and four diseases are all two-star pairs (ROS: 0.087, 0.068, 0.062, 0.095 for T2D, CRC, stroke, and IHD, respectively). CONCLUSION: Consuming 100 g of whole grains per day offers broad protective benefits. However, exceeding this threshold may diminish the protective effects against stroke. Our findings endorse replacing refined grains with whole grains as the main source of daily carbohydrates. REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: We have registered our research in PROSPERO, and the identifier of our meta-analyses is CRD42023447345.

GBA1 as a risk gene for osteoporosis in the specific populations and its role in the development of Gaucher disease.

BACKGROUND: Osteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations. METHODS: We selected 8115 patients with osteoporosis (T-score ≤ - 2.5) and 55,942 healthy individuals (T-score > - 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic reticulum (ER) stress, inflammasome activation, and osteoclastogenesis. An in vitro model of GD patient's cells treated with adeno-associated virus 9 (AAV9)-GBA1 to assess GBA1 enzyme activity, chitotriosidase activity, ER stress, and osteoclast differentiation. Longitudinal dual-energy X-ray absorptiometry (DXA) data tracking bone density in patients with Gaucher disease (GD) undergoing enzyme replacement therapy (ERT) over an extended period. RESULTS: The GBA1 gene variant rs11264345 was significantly associated [P < 0.002, Odds Ratio (OR) = 1.06] with an increased risk of bone disease. Upregulation of Calnexin, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) was positively associated with osteoclastogenesis in patients with GD. In vitro AAV9-GBA1 treatment of GD patient cells led to enhanced GBA1 enzyme activity, reduced chitotriosidase activity, diminished ER stress, and decreased osteoclast differentiation. Long-term bone density data suggests that initiating ERT earlier in GD leads to greater improvements in bone density. CONCLUSIONS: Elevated ER stress and inflammasome activation are indicative of osteoporosis development, suggesting the need for clinical monitoring of patients with GD. Furthermore, disease-associated variant in the GBA1 gene may constitute a risk factor predisposing specific populations to osteoporosis.

Willingness of healthcare providers to perform population-based cancer screening: a cross-sectional study in primary healthcare institutions in Tianjin, China.

OBJECTIVE: To evaluate the willingness of healthcare providers to perform population-based screening in primary healthcare institutions in China. METHODS: Healthcare providers of 262 primary healthcare institutions in Tianjin were invited to fill out a questionnaire consisting of demographic characteristics, workload, and knowledge of, attitude towards and willingness to perform breast, cervical and colorectal cancer screening. Willingness to screen was the primary outcome. Multilevel logistic regression models were conducted to analyse the determinants of healthcare providers' willingness to screen. ORs and 95% CIs were estimated. RESULTS: A total of 554 healthcare providers from 244 institutions answered the questionnaire. 67.2%, 72.1% and 74.3% were willing to perform breast, cervical and colorectal cancer screening, respectively. A negative attitude towards screening was associated with a low willingness for cervical (OR=0.27; 95% CI 0.08, 0.94) and colorectal (OR=0.08; 95% CI 0.02, 0.30) cancer screening, while this was not statistically significant for breast cancer screening (OR=0.30; 95% CI 0.08, 1.12). For breast, cervical and colorectal cancer screening, 70.1%, 63.8% and 59.0% of healthcare providers reported a shortage of staff dedicated to screening. A perceived reasonable manpower allocation was a determinant of increased willingness to perform breast (OR=2.86; 95% CI 1.03, 7.88) and colorectal (OR=2.70; 95% CI 1.22, 5.99) cancer screening. However, this was not significant for cervical cancer screening (OR=1.76; 95% CI 0.74, 4.18). CONCLUSIONS: In China, healthcare providers with a positive attitude towards screening have a stronger willingness to contribute to cancer screening, and therefore healthcare providers' attitude, recognition of the importance of screening and acceptable workload should be optimised to improve the uptake of cancer screening.

Chondroitin sulfate/silk fibroin hydrogel incorporating graphene oxide quantum dots with photothermal-effect promotes type H vessel-related wound healing.

Chronic wounds with bacterial infection present formidable clinical challenges. In this study, a versatile hydrogel dressing with antibacterial and angiogenic activity composite of silk fibroin (SF), chondroitin sulfate (CS), and graphene oxide quantum dots (GOQDs) is fabricated. GOQDs@SF/CS (GSC) hydrogel is rapidly formed through the enzyme catalytic action of horseradish peroxidase. With the incorporation of GOQDs both gelation speed and mechanical properties have been enhanced, and the photothermal characteristics of GOQDs in GSC hydrogel enabled bacterial killing through photothermal treatment (PTT) at ∼51 °C. In vitro studies show that the GSC hydrogels demonstrate excellent antibacterial performance and induce type H vessel differentiation of endothelial cells via the activated ERK1/2 signaling pathway and upregulated SLIT3 expression. In vivo results show that the hydrogel significantly promotes type H vessels formation, which is related to the collagen deposition, epithelialization and, ultimately, accelerates the regeneration of infected skin defects. Collectively, this multifunctional GSC hydrogel, with dual action of antibacterial efficacy and angiogenesis promotion, emerges as an innovative skin dressing with the potential for advancing in infected wound healing.

One-year efficacy of myopia control by the defocus distributed multipoint lens: a multicentric randomised controlled trial.

AIMS: To report the 1-year results of the efficacy of a defocus distributed multipoint (DDM) lens in controlling myopia progression in a multicentre, randomised controlled trial. METHODS: Overall, 168 children aged 6-13 years were recruited and randomly assigned to wear a DDM lens (n=84) or single-vision (SV) lens (n=84) in three centres. Cycloplegic autorefraction (spherical equivalent refraction (SER)) and axial length (AL) were measured. Linear mixed model analysis was performed to compare between-group SER and AL changes. Logistic regression analysis was used to analyse the between-group difference in rapid myopia progression (SER increase≥0.75 D per year or AL growth≥0.40 mm per year). RESULTS: After 1 year, mean changes in SER were significantly lower in the DDM group (-0.47±0.37 D) than in the SV group (-0.71±0.42 D) (p<0.001). Similarly, mean changes in AL were significantly lower in the DDM group (0.21±0.17 mm) than in the SV group (0.34±0.16 mm) (p<0.001). After adjusting for age, sex, daily wearing time and parental myopia, rapid myopia progression risk was higher in the SV group than in the DDM group (OR=3.51, 95% CI: 1.77 to 6.99), especially for children who wore a lens for >12 hours per day, boys and younger children (6-9 years) with ORs (95% CIs) of 10.82 (3.22 to 36.37), 5.34 (1.93 to 14.78) and 8.73 (2.6 to 29.33), respectively. CONCLUSIONS: After 1 year, DDM lenses effectively retarded myopia progression in children. Longer daily wearing time of DDM lens improved the efficacy of myopia control. Future long-term studies are needed for validation. TRIAL REGISTRATION NUMBER: NCT05340699.

Associations of Dynapenic Abdominal Obesity and Frailty Progression: Evidence from Two Nationwide Cohorts.

The associations of dynapenic abdominal obesity and transitions with frailty progression remain unclear among middle-aged and older adults. We included 6937 participants from the China Health and Retirement Longitudinal Study (CHARLS) and 3735 from the English Longitudinal Study of Aging (ELSA). Participants were divided into non-dynapenia and non-abdominal obesity (ND/NAO), abdominal obesity alone (AO), dynapenia alone (D), and dynapenic abdominal obesity (D/AO). Frailty status was assessed by the frailty index (FI), and a linear mixed-effect model was employed to analyze the associations of D, AO, D/AO, and transitions with frailty progression. Participants with AO, D, and D/AO had increased FI progression compared with ND/NAO in both cohorts. D/AO possessed the greatest additional annual FI increase of 0.383 (95% CI: 0.152 to 0.614), followed by D and AO in the CHARLS. Participants with D in the ELSA had the greatest magnitude of accelerated FI progression. Participants who transitioned from ND/NAO to D and from AO to D/AO presented accelerated FI progression in the CHARLS and ELSA. In conclusion, dynapenic abdominal obesity, especially for D/AO and D, presented accelerated frailty progression. Our findings highlighted the essential intervention targets of dynapenia and abdominal obesity for the prevention of frailty progression.

Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome.

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The functional study of a novel MKRN3 missense mutation associated with familial central precocious puberty.

Central precocious puberty (CPP) refers to a syndrome of early puberty initiation with a characteristic increase in the release of gonadotropin-releasing hormone (GnRH); therefore, it is also called GnRH-related precocious puberty. About a quarter of idiopathic central precocious puberty (ICPP) may be familial. Studies suggest that mutations of makorin ring finger protein 3 (MKRN3) can cause familial central precocious puberty (FCPP). In this report, we describe a Chinese female patient carrying a novel MKRN3 variant (c.980G>A/p.Arg327His) and presenting the CPP phenotype. This novel variant attenuated its own ubiquitination, degradation, and inhibition on the transcriptional and translational activity of GNRH1, which was verified through functional tests. We can consider this variant as a loss-of-function mutation, which subsides the inhibition of GnRH1-related signaling and gives rise to GnRH-related precocious puberty.