Decoding the nexus: branched-chain amino acids and their connection with sleep, circadian rhythms, and cardiometabolic health.

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and, either directly or indirectly, overall body health, encompassing metabolic and cardiovascular well-being. Given the heightened metabolic activity of the brain, there exists a considerable demand for nutrients in comparison to other organs. Among these, the branched-chain amino acids, comprising leucine, isoleucine, and valine, display distinctive significance, from their contribution to protein structure to their involvement in overall metabolism, especially in cerebral processes. Among the first amino acids that are released into circulation post-food intake, branched-chain amino acids assume a pivotal role in the regulation of protein synthesis, modulating insulin secretion and the amino acid sensing pathway of target of rapamycin. Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors, competing for a shared transporter. Beyond their involvement in protein synthesis, these amino acids contribute to the metabolic cycles of γ-aminobutyric acid and glutamate, as well as energy metabolism. Notably, they impact GABAergic neurons and the excitation/inhibition balance. The rhythmicity of branched-chain amino acids in plasma concentrations, observed over a 24-hour cycle and conserved in rodent models, is under circadian clock control. The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood. Disturbed sleep, obesity, diabetes, and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics. The mechanisms driving these effects are currently the focal point of ongoing research efforts, since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies. In this context, the Drosophila model, though underutilized, holds promise in shedding new light on these mechanisms. Initial findings indicate its potential to introduce novel concepts, particularly in elucidating the intricate connections between the circadian clock, sleep/wake, and metabolism. Consequently, the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle. They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health, paving the way for potential therapeutic interventions.

Model-based prototype design, establishment and operation of ventilation system for underground gymnasium.

Underground small indoor gymnasiums (USIG) are important public places, it is vital to design and build a very economical and efficient ventilation system for effective closed-loop regulation of temperature and gases concentration at prescribed levels. In the article, the model-based prototype design, establishment and operation were proposed and applied to closed-loop control system of the underground small indoor gymnasiums' ventilation system (USIGVS). First of all, the extended Multiphysics model was developed through feedback connecting the 3D Multiphysics model of air flow rate, temperature, O2 and CO2 concentration with a 0D proportional-integral-derivative (PID) controller via Neumann boundary condition, hence a close-loop USIGVS was constructed for feedback control of temperature and gases concentration in ping-pong USIG. Simultaneously, a cost function sufficiently representing the design requirement was formulated. Then global parameter sensitivity analysis (GPSA) was applied for sensitivity ranking of parameters including geometric parameters of USIGVS and tunable parameters of PID controller. The GPSA proved that sensitivity ordering of the cost function to each parameter was proportional gain (k p ) > derivative gain (k d ) > distance from left inlet to bottom (r) > distance from outlet pipe to bottom (d) > integrative gain (k i ) > distance from upper inlet pipe to left (h), respectively, and the k p , k d and r was the parameter influencing the cost function the most. The optimal parameters determined by both GPSA and response optimization were k p  = 3.17 m4 mol-1 s-1, k d  = 1.49 m4 mol-1, r = 2.04 m, d = 3.12 m, k i  = 0.37 m4 mol-1 s-2 and h = 3.85 m. Finally, the closed-loop USIGVS prototype with optimal parameters was designed and established through real-time simulation. The real-time operation confirmed that the temperature and gases concentrations were robust maintained at prescribed levels with desired dynamic response characteristics and lower power consumption, and the expected requirements were achieved for the design, establishment and operation of closed-loop USIGVS control system prototype.

Can environmental protection tax alleviate the mismatch of financing and investment maturities of heavily polluting enterprises?

The gradual implementation of environmental protection tax policies has incentivized enterprises to engage in green production, effectively promoting China's accelerated achievement of the "dual­carbon" goal. Although environmental protection tax has an important impact on the investment and financing decisions of heavily polluting enterprises (HPE), few studies have focused on the relationship between environmental protection tax and mismatch of financing and investment maturities. In this paper, we consider China's environmental protection tax reform as a "quasi-natural experiment", and utilize the data of A-share listed companies from 2013 to 2022, and use a difference-in-differences (DID) model to assess the impact of this policy on the degree of mismatch of financing and investment maturities of HPE. The study shows that the implementation of the environmental protection tax policy (EPTP) significantly reduces the investment and financing maturities mismatch of the HPE, but this effect "fails" in the high tax rate area, and the policy is difficult to reverse the financing difficulties of the enterprises with a large degree of their own investment and financing maturities mismatch. The mediation mechanism test proves the EPTP acts on the mismatch of financing and investment maturities through two paths: alleviating the financing constraints faced by enterprises and increasing external supervision pressure; the impact of the policy has a time-differentiated effect, which is weakened year by year.

Crocin-1 laden thermosensitive chitosan-based hydrogel with smart anti-inflammatory performance for severe full-thickness burn wound therapeutics.

Burns are the fourth most common type of civilian trauma worldwide, and the management of severe irregular scald wounds remains a significant challenge. Herein, crocin-1 laden hydroxybutyl chitosan (CRO-HBC) thermosensitive hydrogel with smart anti-inflammatory performance was developed for accelerating full-thickness burn healing. The injectable and shape adaptability of the CRO-HBC gel make it a promising candidate for effectively filling scald wounds with irregular shapes, while simultaneously providing protection against external pathogens. The CRO-HBC gel network formed by hydrophobic interactions exhibited an initial burst release of crocin-1, followed by a gradual and sustained release over time. The excessive release of ROS and pro-inflammatory cytokines should be effectively regulated in the early stage of wound healing. The controlled release of crocin-1 from the CRO-HBC gel adequately addresses this requirement for wound healing. The CRO-HBC hydrogel also exhibited an excellent biocompatibility, an appropriate biodegradability, keratinocyte migration facilitation properties, and a reactive oxygen species scavenging capability. The composite CRO-HBC hydrogel intelligently mitigated inflammatory responses, promoted angiogenesis, and exhibited a commendable efficacy for tissue regeneration in a full-thickness scalding model. Overall, this innovative temperature-sensitive CRO-HBC injectable hydrogel dressing with smart anti-inflammatory performance has enormous potential for managing severe scald wounds.

Impact of the novel chlorinated polyfluorinated ether sulfonate, F-53B, on gill structure and reproductive toxicity in zebrafish.

6:2 Chlorinated polyfluorinated ether sulfonate, commonly known as F-53B, is widely used as a mist suppressant in various industries and is frequently detected in the environment. Despite its prevalent presence, the adverse effects of F-53B are not well understood and require future investigation. This study utilized zebrafish embryos and adults to examine the toxic effects of F-53B. Our findings revealed that F-53B impaired gill structure and increased erythrocyte numbers in adult zebrafish. Notably, F-53B demonstrated a higher sensitivity for inducing mortality (LC50 at 96 h) in adult zebrafish compared to embryos. Additionally, F-53B disrupted the expression of critical steroidogenic genes and hindered sex hormone production, which negatively affecting egg production. In conclusion, this study underscores the detrimental impact of F-53B on gill structure and reproductive toxicity in zebrafish, providing valuable insights into its overall toxicity.

[Current Situation and Influencing Factors of Kindergarten Teachers' Participation in Training for Preschool Sex Education].

Objective To understand the current situation and influencing factors of kindergarten teachers' participation in training for preschool sex education in Luzhou city,and provide a basis for improving the sex education literacy of kindergarten teachers in the future. Methods A multi-stage stratified cluster sampling method was adopted,and a questionnaire survey was conducted from December 2021 to January 2022 on the knowledge,attitude,and practice of preschool sex education among all the teachers in 24 kindergartens in Luzhou city. Results Among the 461 teachers,43.0% had participated in lectures/courses/training activities related to preschool sex education;99.1% hoped to participate in lectures/courses/training activities related to preschool sex education;82.6% learned about child sexual knowledge through school education;75.5% expressed the hope to learn about child sexual knowledge through expert training.The results of multivariate Logistic regression showed that except private kindergartens as an inhibiting factor (OR=0.57,95%CI=0.37-0.87,P=0.008),high monthly income (OR=3.52,95%CI=1.13-9.30,P=0.011),more ways to know about sex education knowledge (OR=2.87,95%CI=1.76-4.70,P<0.001),and social support (OR=1.58,95%CI=1.04-2.38, P=0.030) were promoting factors for teachers to participate in the training for preschool sex education. Conclusion The kindergarten teachers presented a participation rate but a high demand for the training for preschool sex education.They mainly obtain the sex education knowledge from school education.The nature of kindergarten,monthly income of teachers,social support situation,and ways of understanding sex education knowledge are the key factors influencing the teachers' participation in the training for preschool sex education.

Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages.

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50-200 µM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice.

Rational design of anthocyanidins-directed near-infrared two-photon fluorescent probes.

Recently, two-photon fluorescent probes based on anthocyanidin molecules have attracted extensive attention due to their outstanding photophysical properties. However, there are only a few two-photon excited fluorescent probes that really meet the requirements of relatively long emission wavelengths (>600 nm), large two-photon absorption (TPA) cross-sections (300 GM), significant Stokes shift (>80 nm), and high fluorescence intensity. Herein, the photophysical properties of a series of anthocyanidins with the same substituents but different fluorophore skeletons are investigated in detail. Compared with b-series molecules, a-series molecules with a six-membered ring in the backbone have a slightly higher reorganization energy. This results in more energy loss upon light excitation, enabling the reaction products to detect NTR through a larger Stokes shift. More importantly, there is very little decrease in fluorescence intensity as the Stokes shift increases. These features are extremely valuable for high-resolution NTR detection. In light of this, novel 2a-n (n = 1-5) compounds are designed, which are accomplished by inhibiting the twisted intramolecular charge transfer (TICT) effect through alkyl cyclization, azetidine ring and extending π conjugation. Among them, 2a-3 gains a long emission spectrum (λem = 691.4 nm), noticeable TPA cross-section (957 GM), and large Stokes shift (110 nm), indicating that it serves as a promising candidate for two-photon fluorescent dyes. It is hoped that this work will offer some insightful theoretical direction for the development of novel high performance anthocyanin fluorescent materials.

Ultrasound-mediated nanobubbles loaded with STAT6 siRNA inhibit TGF-ß1-EMT axis in LUSC cells via overcoming the polarization of M2-TAMs.

M2-like tumor-associated macrophages (M2-TAMs) are closely correlated with metastasis and poor clinical outcomes in lung squamous cell carcinoma (LUSC). Previous studies have demonstrated that STAT6 is an important signaling molecule involved in the polarization of M2-TAMs, EMT is the main way for TAMs to promote tumor progression. However, little attention has been paid to the effect of STAT6 inhibition on LUSC, and it is difficult to achieve an ideal gene silencing effect in immune cells using traditional gene transfection methods. Here, we investigated the optimal concentration of 12-myristic 13-acetate (PMA), lipopolysaccharide (LPS) for the induction of THP-1 into M1-TAMs and M2-TAMs. The expression of pSTAT6 and STAT6 was confirmed in three types of macrophages, and it was demonstrated that pSTAT6 can be used as a specific target of M2-TAMs derived from THP-1. Ultrasound-mediated nanobubble destruction (UMND) is a non-invasive and safe gene delivery technology. We also synthesized PLGA-PEI nanobubbles (NBs) to load and deliver STAT6 small interfering RNA (siRNA) into M2-TAMs via UMND. The results show that the NBs could effectively load with siRNA and had good biocompatibility. We found that UMND enhanced the transfection efficiency of siRNA, as well as the silencing effect of pSTAT6 and the inhibition of M2-TAMs. Simultaneously, when STAT6 siRNA entered M2-TAMs by UMND, proliferation, migration, invasion and EMT in LUSC cells could be inhibited via the transforming growth factor-ß1 (TGF-ß1) pathway. Therefore, our results confirm that UMND is an ideal siRNA delivery strategy, revealing its potential to inhibit M2-TAMs polarization and ultimately treat LUSC.

Knocking down RAD51AP1 enhances chemosensitivity by inhibiting the self-renewal of CD133 positive ovarian cancer stem-like cells.

PURPOSE: This study was designed to investigate the function of RAD51AP1 in the self-renewal and chemosensitivity of CD133 positive (CD133+) ovarian cancer (OC) stem-like cells. METHODS: CD133+ (CD133 positive) OVCAR4 and CD133 negative (CD133-) OVCAR4 cells were separated from OVCAR4 by flow cytometry. Then, the separated CD133+OVCAR4 cells were divided into the following groups: Vector group; RAD51AP1 group; siNC group; si-RAD51AP1 group. Next, sphere-formation assay and colony forming assay were used to evaluate the self-renewal and proliferation ability of cells; western blot to detect the expression of RAD51AP1, transforming growth factor beta 1 (TGF-ß1) and SMAD4 proteins in tissues and cells; qRT-PCR to assess the mRNA levels of sex-determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (OCT4), NANOG and Kruppel-like factor 4 (KLF4). RESULTS: The performance of CD133+OVCAR4 cells was much better than that of CD133-OVCAR4 cells in sphere-formation assay and colony forming assay. Besides, compared with adjacent group and CD133-OVCAR4 cells, the expression level of RAD51AP1 increased significantly in OC group and CD133+OVCAR4 cells. Moreover, the over-expression of RAD51AP1 promoted the self-renewal and proliferation of CD133+OVCAR4 cells. On the contrary, knocking down the expression level of RAD51AP1 could inhibit the self-renewal and proliferation of CD133+OVCAR4 cells and improve the sensitivity of cells to chemotherapy drugs. CONCLUSION: The findings of this study showed that RAD51AP1 was highly expressed in OC tissue and CD133+OVCAR4 cells, and regulated the self-renewal and chemosensitivity of tumor cells through the TGF-ß1/SMAD4 signaling pathway.

Quantum geometry quadrupole-induced third-order nonlinear transport in antiferromagnetic topological insulator MnBi2Te4.

The study of quantum geometry effects in materials has been one of the most important research directions in recent decades. The quantum geometry of a material is characterized by the quantum geometric tensor of the Bloch states. The imaginary part of the quantum geometry tensor gives rise to the Berry curvature while the real part gives rise to the quantum metric. While Berry curvature has been well studied in the past decades, the experimental investigation on the quantum metric effects is only at its infancy stage. In this work, we measure the nonlinear transport of bulk MnBi2Te4, which is a topological anti-ferromagnet. We found that the second order nonlinear responses are negligible as required by inversion symmetry, the third-order nonlinear responses are finite. The measured third-harmonic longitudinal ( V x x 3 ω ) and transverse ( V x y 3 ω ) voltages with frequency 3 ω , driven by an a.c. current with frequency ω , show an intimate connection with magnetic transitions of MnBi2Te4 flakes. Their magnitudes change abruptly as MnBi2Te4 flakes go through magnetic transitions from an antiferromagnetic state to a canted antiferromagnetic state and to a ferromagnetic state. In addition, the measured V x x 3 ω is an even function of the applied magnetic field B while V x y 3 ω is odd in B. Amazingly, the field dependence of the third-order responses as a function of the magnetic field suggests that V x x 3 ω is induced by the quantum metric quadrupole and V x y 3 ω is induced by the Berry curvature quadrupole. Therefore, the quadrupoles of both the real and the imaginary part of the quantum geometry tensor of bulk MnBi2Te4 are revealed through the third order nonlinear transport measurements. This work greatly advanced our understanding on the connections between the higher order moments of quantum geometry and nonlinear transport.

A novel antidepressant homogeneous polysaccharide YLP-1 from Millettia pulchra ameliorates tryptophan metabolism and SCFAs through modulating gut microbiota.

The root of Millettia pulchra (YLS) has been traditionally used as a folk medicine for the treatment of depression and insomnia in the Zhuang nationality of China, and its polysaccharides have potential antidepressant effect. In this study, a novel homogeneous polysaccharide (YLP-1) was purified from the crude polysaccharides of YLS, and it is mainly composed of glucose, arabinose and mannose with molar ratio of 87.25%, 10.77%, and 1.98%, respectively. YLP-1 is a novel α-glucan with the backbone of 1,4-Glcp and branched at C6 of 1,4,6-Glcp to combine 1,4-Manp and 1,5-Araf. The microstructure of YLP-1 displayed a uniform ellipsoidal-like chain morphology and dispersed uniformly in solution. YLP-1 effectively ameliorated depression-like ethological behaviors and restored the decreased catecholamine levels in chronic variable stress (CVS)-induced depression rats. Additionally, it significantly improved the disturbance of gut microbiota induced by CVS stimuli, particularly affecting bacteria that produce short-chain fatty acids (SCFAs), such as bacteria species Lactobacillus spp.. In vitro fermentation study further confirmed that YLP-1 intake could promote SCFAs production by Lactobacillus spp. YLP-1 also mitigated the disruption of tryptophan metabolites in urine and serum. These findings provide evidences for the further development of YLP-1 as a macromolecular antidepressant drug.

Sinonasal teratocarcinosarcoma involving the nasal cavity, unilateral paranasal sinuses, and intracranial invasion: A case report.

BACKGROUND: Sinonasal teratocarcinosarcoma (SNTCS) is a rare and highly invasive neoplasm originating from the nasal cavity and sinuses. Typically, it exhibits an invasive behavior towards adjacent structures; however, in exceptional instances, it may infiltrate the intracranial compartment. Due to the tumor's rarity and lack of distinctive features on computed tomography (CT) and magnetic resonance imaging (MRI) images, SNTCS is often misdiagnosed. CASE SUMMARY: In this study, we present a case of SNTCS in a 56-year-old patient who exhibited unexplained cognitive impairment before admission. CT and MRI scans revealed the presence of a mass in the right nasal cavity, with lesions extending to the right ethmoid sinus and right frontal region. Subsequently, the patient underwent pathological examination for confirmation and received surgical intervention to excise the tumor. The future advancement in our understanding of this disease will significantly contribute to the precise diagnosis and treatment of SNTCS. CONCLUSION: SNTCS is an exceptionally rare malignant tumor that originates from the nasal cavity and paranasal sinuses, presenting a diagnostic challenge due to its non-specific imaging findings. MRI accurately delineates the location, morphological characteristics, size, internal structure, extent of surrounding involvement, and metabolic information of the lesion. These aspects play a pivotal role in the precise localization and qualitative assessment of SNTCS. Nevertheless, a definitive diagnosis still requires a pathological biopsy.

Map-based cloning of LPD, a major gene positively regulates leaf prickle development in eggplant.

KEY MESSAGE: A critical gene for leaf prickle development (LPD) in eggplant was mapped on chromosome E06 and was confirmed to be SmARF10B through RNA interference using a new genetic transformation technique called SACI developed in this study Prickles on eggplant pose challenges for agriculture and are undesirable in cultivated varieties. This study aimed to uncover the genetic mechanisms behind prickle formation in eggplant. Using the F2 and F2:3 populations derived from a cross between the prickly wild eggplant, YQ, and the prickle-free cultivated variety, YZQ, we identified a key genetic locus (LPD, leaf prickle development) on chromosome E06 associated with leaf prickle development through BSA-seq and QTL mapping. An auxin response factor gene, SmARF10B, was predicted as the candidate gene as it exhibited high expression in YQ's mature leaves, while being significantly low in YZQ. Downregulating SmARF10B in YQ through RNAi using a simple and efficient Agrobacterium-mediated genetic transformation method named Seedling Apical Cut Infection (SACI) developed in this study substantially reduced the size and density of leaf prickles, confirming the role of this gene in prickle development. Besides, an effective SNP was identified in SmARF10B, resulting in an amino acid change between YQ and YZQ. However, this SNP did not consistently correlate with prickle formation in eight other eggplant materials examined. This study sheds light on the pivotal role of SmARF10B in eggplant prickle development and introduces a new genetic transformation method for eggplant, paving the way for future research in this field.

Bibliometric and visual analysis of global publications on kaempferol.

Introduction: Kaempferol, a flavonoid found in numerous foods and medicinal plants, offers a range of health benefits such as anti-inflammatory, antioxidant, antiviral, anticancer, cardioprotective, and neuroprotective effects. Methods: Herein, a bibliometric and visual analysis of global publications on kaempferol was performed to map the evolution of frontiers and hotspots in the field. Using the search string TS = kaempferol, bibliometric data for this analysis was extracted from the Web of Science Core Collection database and analyzed using the VOSviewer, CiteSpace, and Scimago Graphica software. Results: As a result, by February 26, 2024, 11,214 publications were identified, comprising articles (n = 10,746, 96%) and review articles (n = 468, 4%). Globally, the annual number of kaempferol publications surpassed 100 per year since 2000, exceeded 500 per year since 2018, and further crossed the threshold of 1,000 per year starting in 2022. The major contributing countries were China, the United States of America, and India, while the top three institutes of the citations of kaempferol were the Chinese Academy of Sciences, Consejo Superio de Investigaciones Cientficas, and Uniersidade do Porto. These publications were mainly published in agricultural and food chemistry journals, food chemistry, and phytochemistry. Discussion: The keywords frequently mentioned include phenolic compounds, antioxidant activity, flavonoids, NF-kappa B, inflammation, bioactive compounds, etc. Anti-inflammation, anti-oxidation, and anti-cancer have consistently been the focus of kaempferol research, while cardiovascular protection, neuroprotection, antiviral, and anti-bacterial effects have emerged as recent highlights. The field of kaempferol research is thriving.

[Research status of lower limb exoskeleton rehabilitation robot].

Lower limb exoskeleton rehabilitation robots are used to improve or restore the walking and movement ability of people with lower limb movement disorders. However, the required functions for patients differ based on various diseases. For example, patients with weak muscle strength require power assistance, patients with spinal cord injuries require motion compensation, patients with gait abnormalities require gait correction, and patients with strokes require neural rehabilitation. To design a more targeted lower limb exoskeleton rehabilitation robot for different diseases, this article summarised and compared existing lower limb exoskeleton rehabilitation robots according to their main functions and the characteristics and rehabilitation needs of various lower limb movement disorders. The correlations between the functions of existing devices and diseases were summarised to provide certain references for the development of new lower limb exoskeleton rehabilitation robots.

Tech-based solutions for health challenges in aging: 25 years of development trends and prospects.

BACKGROUND: As the global population ages, we witness a broad scientific and technological revolution tailored to meet the health challenges of older adults. Over the past 25 years, technological innovations, ranging from advanced medical devices to user-friendly mobile applications, are transforming the way we address these challenges, offering new avenues to enhance the quality of life and well-being of the aging demographic. OBJECTIVE: To systematically review the development trends in technology for managing and caring for elderly health over the past 25 years, and to project future development prospects. METHODS: We conducted a comprehensive bibliometric analysis of literatures related to Tech-based solutions for health challenges in aging, published up to March 18, 2024. The search was performed using the Web of Science Core Collection, covering a span from 1999 to 2024. Our search strategy was designed to capture a broad spectrum of terms associated with aging, health challenges specific to the elderly, and technological interventions. RESULTS: A total of 1,133 publications were found in WoSCC. The publication trend over these 25 years showed a gradual but fluctuating increase. The United States was the most productive country, and participated in international collaboration most frequently. The predominant keywords identified through this analysis include "dementia", "telemedicine", "older-adults", "telehealth", "care". The Keywords with citation bursts from "telemedicine" to "digital health". CONCLUSIONS: The scientific and technological revolution has significantly improved elderly health management, particularly in chronic disease monitoring, mobility, and social connectivity. The momentum for innovation continues to build, with future research likely to focus on predictive analytics and personalized healthcare solutions, further enhancing elderly independence and quality of life.

Tenofovir versus entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma: a reconstructed individual patient data meta-analysis.

Background: Hepatitis B, often leading to Hepatocellular carcinoma (HCC), poses a major global health challenge. While Tenofovir (TDF) and Entecavir (ETV) are potent treatments, their comparative effectiveness in improving recurrence-free survival (RFS) and overall survival (OS) rates in HBV-related HCC is not well-established. Methods: We conducted an individual patient data meta-analysis using survival data from randomized trials and high-quality propensity score-matched studies to compare the impact of Tenofovir (TDF) and Entecavir (ETV) on RFS and OS in HBV-related HCC patients. Data from six databases and gray literature up to 30 August 2023, were analyzed, utilizing Kaplan-Meier curves, stratified Cox models, and shared frailty models for survival rate assessment and to address between-study heterogeneity. The study employed restricted mean survival time analysis to evaluate differences in RFS and OS between TDF-treated and ETV-treated patients. Additionally, landmark analyses compared early (<2 years) and late (≥2 years) tumor recurrence in these cohorts. Results: This study incorporated seven research articles, covering 4,602 patients with HBV-related HCC (2,082 on TDF and 2,520 on ETV). Within the overall cohort, TDF recipients demonstrated significantly higher RFS (p = 0.042) and OS (p < 0.001) than those on ETV. The stratified Cox model revealed significantly improved OS for the TDF group compared to the ETV group (hazard ratio, 0.756; 95% confidence interval, 0.639-0.896; p = 0.001), a result corroborated by the shared frailty model. Over a follow-up period of 1-8 years, no significant difference was noted in the mean time to death between the TDF and ETV groups. The rates of early recurrence did not significantly differ between the groups (p = 0.735). However, TDF treatment was significantly associated with a reduced risk of late recurrence compared to ETV (p < 0.001). In the HCC resection subgroup, the disparities in OS, early, and late recurrence rates between the two treatments paralleled those seen in the overall cohort. Conclusion: Compared to ETV, TDF may enhance OS and reduce late tumor recurrence risk in HBV-related HCC patients receiving curative treatment. However, there was no statistically significant distinction in the timing of tumor recurrence and mortality between patients administered TDF and those prescribed ETV. Systematic Review Registration: http://www.crd.york.ac.uk/prospero/.

NLRC4, inflammation and colorectal cancer (Review).

Chronic inflammation is recognized as a major risk factor for cancer and is involved in every phase of the disease. Inflammasomes are central to the inflammatory response and play a crucial role in cancer development. The present review summarizes the role of Nod­like receptor C4 (NLRC4) in inflammation and colorectal cancer (CRC). Reviews of the literature were conducted using Web of Science, PubMed and CNKI, with search terms including 'NLRC4', 'colorectal cancer', 'auto­inflammatory diseases' and 'prognosis'. Variants of NLRC4 can cause recessive immune dysregulation and autoinflammation or lead to ulcerative colitis as a heterozygous risk factor. Additionally, genetic mutations in inflammasome components may increase susceptibility to cancer. NLRC4 is considered a tumor suppressor in CRC. The role of NLRC4 in CRC signaling pathways is currently understood to involve five key aspects (caspase 1, NLRP3/IL­8, IL­1ß/IL­1, NAIP and p53). The mechanisms by which NLRC4 is involved in CRC are considered to be threefold (through pyroptosis, apoptosis, necroptosis and PANoptosis; regulating the immune response; and protecting intestinal epithelial cells to prevent CRC). However, the impact of NLRC4 mutations on CRC remains unclear. In conclusion, NLRC4 is a significant inflammasome that protects against CRC through various signaling pathways and mechanisms. The association between NLRC4 mutations and CRC warrants further investigation.

Causal relationship between serum metabolites and idiopathic pulmonary fibrosis: Insights from a two-sample Mendelian randomization study.

Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible lung disease with unclear pathological mechanisms. In this study, we utilized bidirectional Mendelian randomization (MR) to analyze the relationship between serum metabolites and IPF, and conducted metabolic pathway analysis. Aim: To determine the causal relationship between serum metabolites and IPF using MR analysis. Methods: A two-sample MR analysis was conducted to evaluate the causal relationship between 824 serum metabolites and IPF. The inverse variance weighted (IVW) method was used to estimate the causal relationship between exposure and results. Sensitivity analysis was conducted using MR Egger, weighted median, and maximum likelihood to eliminate pleiotropy. Additionally, metabolic pathway analysis was conducted to identify potential metabolic pathways. Results: We identified 12 serum metabolites (6 risks and 6 protective) associated with IPF from 824 metabolites. Among them, 11 were known and 1 was unknown. 1-Eicosatrienoylglycophorophospholine and 1-myristoylglycophorophospholine were bidirectional MR positive factors, with 1-myristoylglycophorophospholine being a risk factor (1.0013, 1.0097) and 1-eicosatrienoylglycophorine being a protective factor (0.9914, 0.9990). The four lipids (1-linoleoylglycerophoethanolamine*, total cholesterol in large high-density lipoprotein [HDL], cholesterol esters in very large HDL, and phospholipids in very large HDL) and one NA metabolite (degree of unsaturation) were included in the known hazardous metabolites. The known protective metabolites included three types of lipids (carnitine, 1-linoleoylglycerophoethanolamine*, and 1-eicosatrienoylglycerophophophorine), one amino acid (hypoxanthine), and two unknown metabolites (the ratio of omega-6 fatty acids to omega-3 fatty acids, and the ratio of photoshopids to total lipids ratio in chylomicrons and extremely large very low-density lipoprotein [VLDL]). Moreover, sn-Glycerol 3-phosphate and 1-Acyl-sn-glycero-3-phosphocline were found to be involved in the pathogenesis of IPF through metabolic pathways such as Glycerolide metabolism and Glycerophospholipid metabolism. Conclusion: Our study identified 6 causal risks and 6 protective serum metabolites associated with IPF. Additionally, 2 metabolites were found to be involved in the pathogenesis of IPF through metabolic pathways, providing a new perspective for further understanding the metabolic pathway and the pathogenesis of IPF.