Obesity and its related metabolic diseases have become a major global public health threat, and its rising incidence significantly increases the risk of cardiovascular and cerebrovascular diseases, diabetes and other complications. Pancreatic lipase is a key enzyme that converts food-borne lipids into triglycerides and fatty acids, and the effective inhibition of its activity has become an important strategy for the treatment of obesity. This paper discusses the screening methods of pancreatic lipase inhibitors, and summarizes and reviews the basic principles, advantages and disadvantages and application status of traditional screening methods, modern new screening methods and virtual screening methods. In view of the problems faced by the screening methods of pancreatic lipase inhibitors, future research urgently needs to move towards a collaborative innovation path of multi-technology integration, intelligent screening and complex systematization of traditional Chinese medicine, so as to open up new research paradigms.

Fecal microbiota transplantation （FMT） has been widely used in the treatment of gastrointestinal disorders， particularly Clostridium difficile infection， while there are few reports of its application in the diagnosis and treatment of cirrhotic ascites. This article reports a case of a patient with cirrhotic ascites and chronic diarrhea who received FMT with oral capsules， demonstrating significant short-term efficacy without any adverse reactions， in order to provide a reference for the application of FMT in the treatment of liver diseases.

ObjectiveTo explore the mechanism of modified Xiehuangsan in treating tic disorders （TD） based on microglial polarization and the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor （NF）-κB pathway. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly assigned into six groups： control， model， tiapride （0.025 g·kg^-1）， and low-， medium-， and high-dose （12， 24， 48 g·kg^-1， respectively） modified Xiehuangsan， with 12 rats in each group. Except the control group， the other groups received intraperitoneal injection of 3，3'-iminodipropionitrile （IDPN） for 7 consecutive days for the modeling of TD. After successful modeling， the control and model groups were given normal saline via gavage， and the other groups were administrated with corresponding drugs by gavage. After 28 days of continuous intervention， rat behaviors were observed， and the modified Xiehuangsan group showing the best anti-TD effect was selected for deciphering the treatment mechanism. Hematoxylin and eosin staining was conducted to observe morphological changes in the rat striatum. Immunohistochemistry was employed to detect the expression of CD16 and CD206 in the striatum. Real-time PCR was employed to measure the mRNA levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， IL-4， TLR4， MyD88， and NF-κB p65 in the striatum. Western blot was employed to determine the protein levels of ionized calcium-binding adapter molecule 1 （Iba1）， Fc receptor family for immunoglobulin （Ig）G type Ⅲ （CD16）， mannose receptor （CD206）， TLR4， MyD88， and NF-κB p65 in the striatum. ResultsCompared with the control group， the model group showed increased stereotyped behaviors， locomotor activity， total movement distance， and movement speed， shortened resting time （P<0.01）， and noticeable pathological changes in the striatum. Compared with the model group， the tiapride group and modified Xiehuangsan groups exhibited reduced stereotyped behavior， locomotor activity， total movement distance， and movement speed， prolonged resting time （P<0.05， P<0.01）， and alleviated pathological changes in the striatum. Among the modified Xiehuangsan groups， the high-dose group had the best intervention effect and the mildest pathological changes. Therefore， the high-dose group was selected for further research. Compared with the control group， the modeling of TD increased Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the mRNA levels of IL-1β and TNF-α （P<0.05， P<0.01）， down-regulated the mRNA level of IL-4 （P<0.05）， up-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.05， P<0.01）， and up-regulated the protein level of NF-κB p65 （P<0.01）. Compared with the model group， modified Xiehuangsan reduced Iba1 and CD16 expression （P<0.05， P<0.01）， up-regulated the protein level of CD206 （P<0.05， P<0.01）， down-regulated the mRNA levels of IL-1β and TNF-α （P<0.05）， up-regulated the mRNA level of IL-4 （P<0.01）， and down-regulated the mRNA and protein levels of TLR4， MyD88， and NF-κB p65 （P<0.05， P<0.01）. ConclusionModified Xiehuangsan demonstrated a definite therapeutic effect on TD in rats. It may reduce neuroinflammation in TD rats by regulating the polarization of microglia in the striatum via the TLR4/MyD88/NF-κB signaling pathway.

Vitrification cryopreservation technology converts the liquid water in biological samples into glassy solids through ultra-rapid cooling. In this review, the core research of vitrification cryopreservation technology was mainly reviewed, such as the optimization of cryoprotectant formulations, the improvements to temperature control methods, the innovative carrier designs and the improvements to rewarming technology. The application status and issues in the fields of organ preservation, tumor research, reproductive medicine and rare cell preservation were also summarized. By combining the technical principles with glassy state detection methods, a theoretical basis was provided for optimizing the technical system and expanding application scenarios, thereby promoting its large-scale application in clinical and biological sample libraries.

Pulmonary vascular remodeling is the core pathological feature in the onset and pro-gression of pulmonary arterial hypertension(PAH).Currently,there is no well-defined therapeutic strategy that can effectively delay or reverse this process.Despite the widespread clinical application of targeted vasodilator drugs,patients still face a high risk of mortality and adverse cardiovascular e-vents,suggesting an urgent need to explore new pathological mechanisms and therapeutic targets.In recent years,the relationship between dyslipidemia and PAH has garnered increasing attention.This article aimed to review the role of lipid metabolism disorders in pulmonary vascular remodeling in pul-monary arterial hypertension and its underlying mechanism,with the hope of providing new interven-tion targets for the treatment of PAH,thereby improving patient survival rates and quality of life.

Objective:To explore the role of lactate in Superoxide dismutase 2 (SOD2) lactylation in cerebral ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomLy (random number) divided into 4 groups: sham operation group (Sham group), Middle Cerebral Artery Occlusion/Reperfusion group (MCAO/R group), Middle Cerebral Artery Occlusion/Reperfusion+2-Deoxy-D-glucose group (MCAO/R+2-DG group), Middle Cerebral Artery Occlusion/Reperfusion+sodium lactate group (MCAO/R+Nala group). Cerebral ischemia reperfusion injury model was established in the mice of MCAO/R group using the thread occlusion. In the MCAO/R+2-DG group, mice received an intraperitoneal injection of 250 mg/kg of 2-DG 90 min before ischemia. Mice in the MCAO/R+ Nala group was given an intraventricular injection of 2 μL of 100 mmol/L Nala 24 h before ischemia. Commercial kits was used to detect lactate levels, Hematoxylin & Eosin Staining (HE) was employed to observe cell morphology, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed to assess cell apoptosis, and immunofluorescence was utilized to detect reactive oxygen species (ROS). Western blot was conducted to measure SOD2, Superoxide Dismutase 2 Lysine 114 Lactylation(SOD2-K114la), Iron regulatory protein 2(IRP2) and transferrin receptor protein 1(TFR1) levels. The above indicators were analyzed and compared by one-way variance.Results:Compared with the Sham group, the MCAO/R group showed increased levels of lactate, SOD2-K114la, TUNEL positive rate, ROS, IRP2 and TFR1[lactate: (0.608±0.064) vs. (0.376±0.030), P<0.005; SOD2-K114la: (2.311±0.146) vs. (1.009±0.073), P<0.0005; TUNEL positive rate: (35.420±2.832) vs. (0.294±0.147), P<0.0001; ROS: (3.415±0.229) vs. (1.166±0.155), P<0.0001; IRP2: (1.735±0.125) vs. (1.000±0.000), P<0.0001; TFR1: (1.611±0.058) vs. (1.000±0.000), P<0.0001], while SOD2 decreased[(0.545±0.062) vs. (1.082±0.088), P<0.0001]. HE staining indicated brain damage. Compared with the MCAO/R group, the MCAO/R+2-DG group showed reduced levels of lactate, SOD2-K114la, TUNEL positive rate, ROS, IRP2, and TFR1[lactate: (0.453±0.047) vs. (0.608±0.064), P<0.05; SOD2-K114la: (1.764±0.188) vs. (2.311±0.146), P<0.05; TUNEL positive rate: (23.800±3.168) vs. (35.420±2.832), P<0.005; ROS: (2.640±0.213) vs. (3.415±0.229), P<0.005; IRP2: (1.463±0.055) vs. (1.735±0.125), P<0.05; TFR1: (1.252±0.081) vs. (1.611±0.058), P<0.005], with higher level of SOD2 [(0.727±0.026) vs. (0.545±0.062), P<0.05]. Meanwhile, HE staining indicated reduced damage. Compared with the MCAO/R group, the MCAO/R+Nala group showed increased levels of lactate, SOD2-K114la, TUNEL positive rate, ROS, IRP2 and TFR1[lactate: (1.021±0.051) vs. (0.608±0.064), P<0.0001; SOD2-K114la: (3.479±0.275) vs. (2.311±0.146), P<0.0005; TUNEL positive rate: (53.430±3.551) vs. (35.420±2.832), P<0.0001; ROS: (4.687±0.253) vs. (3.415±0.229), P<0.0001; IRP2: (2.463±0.117) vs. (1.735±0.125), P<0.0001; TFR1: (2.209±0.094) vs. (1.611±0.058), P<0.0001], with decreased levels of SOD2 [(0.286±0.040) vs. (0.545±0.062), P<0.0001]. And HE staining revealed worsened braindamage. Conclusions:Increased lactate levels can enhance the lactylation of SOD2, exacerbating brain damage after Cerebral ischemia reperfusion injury(CIRI). Inhibiting lactate production may alleviate brain injury by regulating iron Metabolism.

Objective To analyze the effects of the histone deacetylase inhibitor suberoylanilide hydroxamic acid(SAHA)on the secondary metabolites of the entomopathogenic fungus Samsoniella hepiali CDB9-31 using thin-layer chromatography(TLC)and high-performance liquid chromatography(HPLC).Methods The fermentation products of Samsoniella hepiali CDB9-31 treated with epigenetic modifiers were separated and purified using methods such as silica gel column chromatography,Sephadex column chromatography and reversed-phase column chromatography.The structures of the compounds were elucidated using modern spectroscopic analysis methods.The antimicrobial activity of the obtained monomeric compounds was determined using the filter paper disc diffusion method.Results The TLC and HPLC analyses of its fermentation extracts revealed that SAHA could induce the strain to produce more diverse array of secondary metabolites,and 11 monomeric compounds were isolated and identified as follows:N'-phenyloctanediamide(1),5-Phenylcarbamoyl-pentanoic(2),ergosterol(3),5,8-Epidioxy-5α,8α-ergosta-6,22E-diene-3β-ol(4),1-monolinolein(5),(4E,8E)-2-N-(2-Hydro-xypalmitoyl)-1-O-(β-D-glucopyranosyl)-9-methyl-4,8-sphingadienine(6),Ergosterol peroxide 3-O-β-D-glucopyranoside(7),(22E,24R)-7,22-diene-3β,5α,6β-ergostatriol(8),(2S,2'R,3R,4E,8E)-N-2'-Hydroxyhexadecanoyl-2-amion-9-methyl-4,8-octadecadiene-1,3-diol(9),Adenosine(10),D-Glulopyranose(11).Compounds 1 and 2 were derivatives of SAHA,and it was speculated that the special metabolic environment of CDB9-31 caused the biotransformation of SAHA.Except for compound 3,all other compounds were isolated from this genus for the first time.The antibacterial activity results showed that six of these compounds exhibited varying degrees of inhibitory effects against at least one pathogenic bacterium.Conclusion This study has enriched the chemical diversity of secondary metabolites from the entomopathogenic fungus Samsoniella hepiali.

Dysfunction of the diaphragm is a common problem in mechanically ventilated patients and is closely related to various adverse outcomes.This review summarizes the evaluation methods of diaphragm function,the association between diaphragm dysfunction and adverse clinical outcomes in critically ill mechanically ventilated patients,and the protective effect of diaphragm function on adverse outcomes related to mechanical ventilation.The aim is to provide references for medical staff to optimize evaluation techniques,develop personalized nursing plans,and improve patients' quality of life and health outcomes.

OBJECTIVE To investigate the effect of hyperoside on high glucose-induced excessive proliferation of retinal endo-thelial cells(RECs)and its possible mechanism.METHODS Diabetic retinopathy(DR)models were established in male Sprague-Dawley(SD)rats.DR rats were treated with low-and high-dose hyperoside(DR+L-HY group and DR+H-HY group).Additional-ly,the normal control(NC)group,DR non-intervention(DR)group and DR+calcium dobesilate intervention(DR+CD)group were set up.The differences in the number of RECs in retinal blood vessels were observed and compared among all groups after intervention.In addition,RECs were inoculated into cell culture plates after normal culture and subculture.They were divided into 5 groups according to different treatments:normal glucose(NG)group,high glucose(HG)group,mannitol(MT)group,high glucose+low concentration of hyperoside(HG+H100)group and high glucose+high concentration of hyperoside(HG+H400)group.The activ-ity,cell migration and tubule formation of RECs in each group were detected and compared by CCK-8,cell migration and tubule for-mation assays.Western blot and qPCR were used to detect the expression of NADPH Oxidase 4(NOX4)and thioredoxin interacting protein(TXNIP)in each group.RESULTS The number of RECs in the DR group was significantly increased compared to the NC group(P<0.01).In contrast,the DR+L-HY,DR+H-HY,and DR+CD groups all showed significant decreases in RECs number compared to the DR group(P<0.05,P<0.01),and the reduction of RECs in the DR+H-HY group was significantly greater than that in the DR+L-HY group(P<0.05).Furthermore,the cell activity,migration number and tube formation number of RECs in the HG group were significantly higher than those in the NG group(P<0.05,P<0.01).The protein and mRNA expression levels of NOX4 and TXNIP in the HG group were also significantly higher than those in the NG group(P<0.01).However,the RECs activity,RECs mi-gration number and tube formation number in the HG+H100 group and the HG+H400 group were significantly lower than those in the HG group(P<0.05,P<0.01).The expression levels of NOX4 and TXNIP in both groups were significantly lower than those in the HG group(P<0.05,P<0.01),and the RECs activity,migration number,tube formation number,and the expression of NOX4 and TXNIP in the HG+H400 group were further significantly decreased compared with those in the HG+H100 group(P<0.01).CONCLU-SION Hyperoside could significantly inhibit the high glucose-induced excessive proliferation of RECs.The mechanism may be relat-ed to the inhibition of NOX4/TXNIP activation in high-glucose environment.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*