Piezo1 is a Ca²⁺-permeable mechanosensitive ion channel that plays a central role in mechanosensing and signal transduction in dental and periodontal tissues. In tooth tissue, Piezo1 is a key factor mediating dentin sensitive pain. The flow of dentinal tubule fluid induced by external stimulation can activate the Piezo1 channel on odontoblasts, triggering neuronal signals through the pannexin-1-purinergic 2X3 receptor (PANX-1-P2X3) receptor axis, resulting in pain perception. In addition, Piezo1 has a dual regulatory role in the process of pulp inflammation and repair : on the one hand, its expression is up-regulated in an inflammatory environment, which may aggravate pain sensitivity ; on the other hand, it activates the migration, proliferation and odontogenic differentiation of dental pulp stem cells by mediating Ca²⁺influx, ATP release and downstream purinergic 2X7 receptor (P2X7R), MEK / ERK signaling pathways, thereby promoting reparative dentin formation. In periodontal tissue, Piezo1 plays a central role in maintaining periodontal tissue homeostasis and regulating alveolar bone remodeling by sensing mechanical stimuli such as bite force. During orthodontic tooth movement, Piezo1 promotes osteogenic differentiation by activating Wnt / Ca²⁺, Notch and other pathways on the tension side. It affects osteoclast activity by regulating receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) balance on the pressure side. At the same time, Piezo1 is also a key regulator of periodontal immune microenvironment. It is expressed in immune cells such as macrophages, neutrophils and dendritic cells. Its activation can promote the polarization of macrophages to pro-inflammatory M1 type, enhance the release of pro-inflammatory factors and matrix metalloproteinases, and thus aggravate the inflammatory destruction of periodontal tissue.In view of its multiple functions, Piezo1 has become a potential therapeutic target, including local or systemic application of its inhibitors, mechanical intervention, physical therapy, gene therapy and stem cell therapy, showing a broad clinical transformation prospect in the treatment of oral diseases. In this paper, the structural characteristics, signal transduction mechanism of Piezo1 and its expression distribution, function and regulatory network in tooth tissue and periodontal tissue are reviewed, so as to provide ideas for the development of oral disease treatment strategies targeting Piezo1.

Objective To investigate the relationship between the comorbidity of dyslipidemia, hypertension and diabetes and lifestyle of adult residents in Hebei Province in 2018, and to provide reference for the development of chronic diseases prevention measures. Methods Using data from the surveillance of chronic diseases and their risk factors among adults in Hebei in 2018, 7 711 permanent residents aged ≥18 years were selected as the research subjects. Multivariate logistic regression analysis was used to analyze the relationship between the comorbidity of dyslipidemia, hypertension, and diabetes and lifestyle in adult residents. Results A total of 7 711 subjects aged ≥18 years were included in 2018. The comorbidity rates of hypertension and dyslipidemia, diabetes and dyslipidemia, and hypertension and diabetes were 16.88%, 7.91%, and 8.13%, respectively. The comorbidity rate of hypertension, diabetes, and dyslipidemia was 22.65%. These comorbidity rates increased with age and BMI. Multivariate logistic regression results showed that male, age, overweight/obesity, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep problems were risk factors for the comorbidity of the "three highs". Conclusion The prevalence of the "three highs" comorbidities is relatively high in Hebei Province, and there are multiple common risk factors. Maintaining a healthy lifestyle and implementing comprehensive prevention and control measures are the key to improving the health level of residents.

Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

In the century-long evolution of insulin pharmaceuticals, each transformative advancement in this drug class has been closely tied to the ability to obtain new insulin isoforms for research. Despite this, the recently discovered naturally occurring isoforms of glycosylated human insulin have remained largely unattainable for proper characterization. Herein, we demonstrate for the first time that total chemical synthesis can be used to generate all isoforms. This achievement required maintaining the correct positions of the interchain disulfide bonds while effectively removing protecting groups on complex glycans. Notably, the availability of seven glycoforms reveals the important effects of natural sialylated glycans in suppressing insulin self-association and enhancing its solubility, surpassing the performance of currently employed rapid-acting insulin drugs. This work not only offers a readily adaptable platform for exploring natural O-glycosylation in other therapeutic proteins and peptides but also lays the groundwork for further research into harnessing natural glycosylation for therapeutic applications.

In this study, we employed a combination of genome mining and heteronuclear single quantum coherence (HSQC)-based small molecule accurate recognition technology (SMART) technology to search for fernane-type triterpenoids. Initially, potential endophytic fungi were identified through genome mining. Subsequently, fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction. These triterpenoids were then obtained through targeted isolation and identification. Finally, their antifungal activity was evaluated. As a result, three fernane-type triterpenoids, including two novel compounds, along with two new sesquiterpenes and four known compounds were isolated from one potential strain, Diaporthe discoidispora. Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector (ECD) analysis. Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.
Triterpenes/isolation & purification* ; Antifungal Agents/isolation & purification* ; Molecular Structure ; Candida albicans/drug effects* ; Ascomycota/genetics* ; Magnetic Resonance Spectroscopy ; Aspergillus niger/drug effects* ; Genome, Fungal ; Microbial Sensitivity Tests

Nonalcoholic steatohepatitis （NASH） is a chronic liver disease with the main pathological features of hepatic steatosis， inflammatory cell infiltration， and interstitial fibroplasia， and it is an important risk factor for liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. NOD-like receptor protein 3 （NLRP3） inflammasome is the core of innate immunity， and the abnormal activation of NLRP3 inflammasome is closely associated with the development and progression of NASH， which involves multiple links such as inflammatory response and oxidative stress. A large number of studies have shown that the active ingredients of traditional Chinese medicine （TCM） and TCM compound prescriptions can improve oxidative stress， regulate lipid metabolism， and alleviate liver inflammation by regulating NLRP3 inflammasome. TCM treatment applied in clinical practice has achieved a good therapeutic effect， while inflammasome is one of the key pathways or targets for TCM in improving NASH. This article reviews the mechanism of action of NLRP3 inflammasome in NASH and the research advances in TCM intervention of NLRP3 inflammasome， in order to provide ideas for the clinical TCM treatment of NASH， as well as reference targets and research directions for the research and development of new TCM drugs.

Cardiotocography (CTG) is a non-invasive and important tool for diagnosing fetal distress during pregnancy. To meet the needs of intelligent fetal heart monitoring based on deep learning, this paper proposes a TWD-MOAL deep active learning algorithm based on the three-way decision (TWD) theory and multi-objective optimization Active Learning (MOAL). During the training process of a convolutional neural network (CNN) classification model, the algorithm incorporates the TWD theory to select high-confidence samples as pseudo-labeled samples in a fine-grained batch processing mode, meanwhile low-confidence samples annotated by obstetrics experts were also considered. The TWD-MOAL algorithm proposed in this paper was validated on a dataset of 16 355 prenatal CTG records collected by our group. Experimental results showed that the algorithm proposed in this paper achieved an accuracy of 80.63% using only 40% of the labeled samples, and in terms of various indicators, it performed better than the existing active learning algorithms under other frameworks. The study has shown that the intelligent fetal heart monitoring model based on TWD-MOAL proposed in this paper is reasonable and feasible. The algorithm significantly reduces the time and cost of labeling by obstetric experts and effectively solves the problem of data imbalance in CTG signal data in clinic, which is of great significance for assisting obstetrician in interpretations CTG signals and realizing intelligence fetal monitoring.
Humans ; Pregnancy ; Female ; Cardiotocography/methods* ; Deep Learning ; Neural Networks, Computer ; Algorithms ; Fetal Monitoring/methods* ; Heart Rate, Fetal ; Fetal Distress/diagnosis* ; Fetal Heart/physiology*

BACKGROUND:It has been found that internal factors such as anatomical structure,hormone level and neuromuscular function of athletes are closely related to the risk of anterior cruciate ligament injuries,and external factors such as the material of the playing field also become one of the risk factors affecting the occurrence of non-contact anterior cruciate ligament injuries,but they are relatively under-attended in the current studies. OBJECTIVE:To explore effects of artificial turf versus natural grass on the biomechanical performance of the lower limbs in young females during jump-landing. METHODS:According to the test needs,artificial turf and natural grass in accordance with the standards of GB/T 20033.3-2006 and GB/T 19995.1-2005 were leveled and fixed on two three-dimensional force measuring platforms.Twenty-one young females were voluntarily recruited and completed the jump-landing task on the artificial turf and natural grass.Subjects stood on the steps and then jumped forward,jumped down to the force measuring platform and immediately jumped with full force to the force measuring platform again.The two landings were required to fall to the two force measuring platforms,and the whole jumping action was considered successful without any pause.The kinematic,kinetic and electromyographic data of the lower limbs during the landing process were collected synchronously to compare and analyze the differences between the two. RESULTS AND CONCLUSION:In terms of kinetics,posterior and vertical ground reaction force at the initial landing moment during jump-landing on the natural grass were significantly lower than those on the artificial turf(P＜0.05,P＜0.01),as well as at the peak ground reaction force moment(P＜0.05,P＜0.05).Additionally,the knee flexion moment when jump-landing on the natural grass was higher than that on the artificial turf(P＜0.01).In terms of electromyography,within 100 ms after the initial landing moment,the electromyography activity levels of medial femoris muscle,lateral femoris muscle and anterior tibialis muscle when jump-landing on the natural grass were significantly lower than those on the artificial turf(P＜0.05,P＜0.01,P＜0.05).To conclude,compared with the natural grass,jump-landing on the artificial turf leads to an change in biomechanical performance that will cause an increase in anterior cruciate ligament tension.

Objective:To evaluate the effectiveness of opioid-free anesthesia on postoperative outcomes in elderly patients following laparoscopic cholecystectomy.Methods:In this randomized controlled trial, 90 patients of either sex, aged 65-75 yr, with a body mass index of 18.5-23.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective laparoscopic cholecystectomy, were divided into 2 groups ( n=45 each) using a table of random numbers: conventional general anesthesia group (GA group) and opioid-free anesthesia group (OFA group). Anesthesia was induced with intravenous etomidate, sufentanil and cisatracurium besylate and maintained with infusion of propofol and remifentanil combined with inhalation of sevoflurane in GA group. In OFA group, bilateral ultrasound-guided transversus abdominis plane block was performed via the posterior gluteal approach (injection of 0.25% ropivacaine 20 ml respectively) before anesthesia induction, anesthesia was induced with intravenous dexmedetomidine, esketamine, etomidate and cisatracurium besylate and maintained with infusion of dexmedetomidine, esketamine and propofol combined with inhalation of sevoflurane. In both groups, mechanical ventilation was performed with a laryngeal mask airway after anesthesia induction, and ketorolac tromethamine 30 mg (for postoperative analgesia) and metoclopramide 10 mg (to prevent postoperative nausea and vomiting) were intravenously injected at the end of surgery. The intraoperative adverse cardiovascular events, emergence time, laryngeal mask airway removal time, time of postanesthesia care unit stay, and postoperative rescue analgesia, nausea and vomiting and delirium were recorded. Results:No gallbladder cardiac reflex was found during operation in either group. Compared with GA group, the incidence of intraoperative bradycardia (11% versus 22%) was significantly increased ( P<0.05), the incidence of intraoperative hypotension and postoperative nausea, vomiting and delirium (17% versus 8%, 29% versus 16%, 16% versus 4% and 18% versus 4%), and requirements for rescue analgesia and antiemetics (31% versus 7% and 13% versus 4%) were decreased ( P<0.05), the postoperative emergence time, time of laryngeal mask airway removal and time of postanesthesia care unit stay were prolonged ( P<0.05), and no statistically significant difference was found in discharge time in OFA group ( P>0.05). Conclusions:The results of this study, as a single-center, small-sample randomized controlled trial, indicate that referenced to conventional general anesthesia, opioid-free anesthesia (esketamine-dexmedetomidine based anesthesia combined with bilateral transversus abdominis plan block) can improve the short-term postoperative outcomes to a certain extent in elderly patients following laparoscopic cholecystectomy.

Objective:To investigate the effects of body habitus and gender on radiation dose assessment methodologies in low-dose chest CT, with particular emphasis on clarifying discrepancies among various dose quantification approaches and their associations with patient characteristics.Methods:Imaging data from 19 371 patients who underwent low-dose chest CT at the First Affiliated Hospital of Chongqing Medical University between January 2021 and January 2024 were retrospectively analyzed. Patients were categorized into eight groups based on water-equivalent diameter (WED) and gender: Group A (150 mm≤WED<210 mm; 71 males, 1 032 females), Group B (210 mm≤WED<260 mm; 4 525 males, 8 005 females), Group C (260 mm≤WED<300 mm; 4 234 males, 1 105 females), and Group D (WED≥300 mm; 357 males, 42 females). WED, size-specific dose estimate (SSDE), and organ dose-based effective dose(ED Radimetrics)were calculated using Radimetrics software. Scanner-reported dose metrics, including volume CT dose index (CTDIvol), dose-length product (DLP), and DLP-derived effective dose(ED DLP), were recorded. The ratios of SSDE/CTDIvol and ED Radimetrics/ED DLP were used to quantify discrepancies between dose evaluation methods. The Kruskal-Wallis test was employed to analyze dose metric differences across WED groups within the same gender, while the Wilcoxon rank-sum test compared gender-based differences within each WED group. Results:All dose metrics significantly increased with WED for both genders (all P<0.05). Within the same WED group, ED Radimetrics was significantly higher in females ( P<0.05), whereas ED DLP was higher in males ( P<0.05). The SSDE/CTDIvol ratio decreased with increasing WED, declining from 1.74 in Group A to 1.16 in Group D for females and from 1.68 to 1.12 for males. The ED Radimetrics/ED DLP ratio exhibited a decreasing trend with WED in females (1.82 to 1.30) but showed an initial increase in males (1.29 in Group A to 1.31 in Group B) before decreasing to 0.94 in Group D (all intergroup P<0.05). SSDE/CTDIvol and ED Radimetrics/ED DLP ratios of females were consistently higher than that of males within each WED group (all P<0.05). Conclusions:Patient body habitus and gender significantly influence radiation dose distribution in low-dose chest CT. Larger body habitus is associated with higher radiation doses, while females receive greater ED Radimetrics than males within comparable body habitus. Traditional dose metrics (CTDIvol and ED DLP) were underestimated for patients with small body sizes and female individuals.