Correlation between genotypes of Orientia tsutsugamushi and clinical characteristics of patients with scrub typhus in Guangzhou,China

Objective:To explore the correlation between genotypes of Orientia(O.)tsutsugamushi and clinical characteristics of scrub typhus patients.Methods:Clinical data of patients with scrub typhus admitted to different types of medical institutions in Guangzhou from September 2012 to December 2016 were collected using medical records.Demographic data,clinical manifestations,as well as hematological and biochemical indicators of patients infected with different genotypes were analyzed and compared.Results:A total of 192 patients were included in this study,including 121 patients with Karp genotype of O.tsutsugamushi infection(63.0%),36 patients with Gilliam genotype(19.0%),23 patients with Kato genotype(12.0%),and 12 patients with TA763 genotype(6.0%)infection.The median value of albumin in patients with Karp genotype infection was significantly lower than that of Gilliam-infected patients(P=0.032).Patients with Karp genotype infection had a significantly longer hospital stay(9 days)than those with Gilliam genotype(7 days)(P=0.009)and Kato genotype infection(6 days)(P=0.005).Karp-infected patients also represented for the largest number of patients with complicated organ involvement(88/133,66.2%).Furthermore,Karp-infected patients had higher risk of developing multiple organ dysfunction syndrome(18.2%)and requiring intensive care unit treatment(15.9%).Besides,patients with Gilliam genotype(8 days)and TA763 genotype infection(7.5 days)had shorter fever duration than those with Karp genotype(9 days)and Kato genotype(9 days)infection,respectively.Conclusions:Genotypes of Orientia tsutsugamushi were associated with varying clinical manifestations,organ involvement,and treatment outcomes,suggesting that genotypes ranged in virulence.

Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

Exploring gut microbiota as a novel therapeutic target in Crohn’s disease: Insights and emerging strategies

Extensive research has investigated the etiology of Crohn’s disease(CD),encompassing genetic predisposition,lifestyle factors,and environmental triggers.Recently,the gut microbiome,recognized as the human body’s second-largest gene pool,has garnered significant attention for its crucial role in the patho-genesis of CD.This paper investigates the mechanisms underlying CD,focusing on the role of‘creeping fat’in disease progression and exploring emerging therapeutic strategies,including fecal microbiota transplantation,enteral nutri-tion,and therapeutic diets.Creeping fat has been identified as a unique patho-logical feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome.We characterize this dysbiotic state by identi-fying key microbiome-bacteria,fungi,viruses,and archaea,and their contributions to CD pathogenesis.Additionally,this paper reviews contemporary therapies,empha-sizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions.By elucidating the complex interactions between host-microbiome dynamics and CD pathology,this article aims to advance our under-standing of the disease and guide the development of more effective therapeutic strategies for managing CD.

Advances in Graphene‑Based Electrode for Triboelectric Nanogenerator

With the continuous development of wearable electronics,wireless sensor networks and other micro-electronic devices,there is an increasingly urgent need for miniature,flexible and efficient nanopower generation technology.Triboelectric nanogenerator(TENG)technology can convert small mechanical energy into electricity,which is expected to address this problem.As the core component of TENG,the choice of electrode materials significantly affects its performance.Traditional metal electrode materials often suffer from problems such as durability,which limits the further application of TENG.Graphene,as a novel electrode material,shows excellent prospects for application in TENG owing to its unique structure and excellent electrical properties.This review systematically summarizes the recent research progress and application prospects of TENGs based on graphene electrodes.Various precision processing methods of graphene electrodes are introduced,and the applications of graphene electrode-based TENGs in various scenarios as well as the enhancement of graphene electrodes for TENG performance are discussed.In addition,the future development of graphene electrode-based TENGs is also prospectively discussed,aiming to promote the continuous advancement of graphene electrode-based TENGs.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Protein nanoparticles as potent delivery vehicles for polycytosine RNA-binding protein one

Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes pathology.This condition could be protected by the upregulation of the gene encoding polycytosine RNA-binding protein 1(PCBP1).Additionally,Ma et al used a lentivirus infection system to express PCBP1.As the authors’method of administration can be improved in terms of stability and cost,we propose delivering PCBP1 to treat type 2 diabetic osteoporosis by encapsulating it in protein nanoparticles.First,PCBP1 is small and druggable.Second,intravenous injection can help deliver PCBP1 across the mucosa while avoiding acid and enzyme-catalyzed degradation.Furthermore,incorporating PCBP1 into nanoparticles prevents its interaction with water or oxygen and protects PCBP1’s structure and activity.Notably,the safety of the protein materials and the industrialization techniques for large-scale production of protein nanoparticles must be comprehensively investigated before clinical application.

Molecular mechanism of pancreatic ductal adenocarcinoma:The heterogeneity of cancer-associated fibroblasts and key signaling pathways

Pancreatic ductal adenocarcinoma stands out as an exceptionally fatal cancer owing to the complexities associated with its treatment and diagnosis,leading to a notably low five-year survival rate.This study offers a detailed exploration of epidemiological trends in pancreatic cancer and key molecular drivers,such as mutations in CDKN2A,KRAS,SMAD4,and TP53,along with the influence of cancer-associated fibroblasts(CAFs)on disease progression.In particular,we focused on the pivotal roles of signaling pathways such as the transforming growth factor-βand Wnt/β-catenin pathways in the development of pancreatic cancer and investigated their application in emerging therapeutic strategies.This study provides new scientific perspectives on pancreatic cancer treatment,especially in the development of precision medicine and targeted therapeutic strategies,and demonstrates the importance of signaling pathway research in the development of effective therapeutic regimens.Future studies should explore the subtypes of CAFs and their specific roles in the tumor microenvironment to devise more effective therapeutic methods.

Prussian Blue Analogue‑Templated Nanocomposites for Alkali‑Ion Batteries:Progress and Perspective

Lithium-ion batteries(LIBs)have dominated the portable electronic and electrochemical energy markets since their commercialisation,whose high cost and lithium scarcity have prompted the development of other alkali-ion batteries(AIBs)including sodium-ion batteries(SIBs)and potassium-ion batteries(PIBs).Owing to larger ion sizes of Na^(+)and K^(+)compared with Li^(+),nanocomposites with excellent crystallinity orientation and well-developed porosity show unprecedented potential for advanced lithium/sodium/potassium storage.With enticing open rigid framework structures,Prussian blue analogues(PBAs)remain promising self-sacrificial templates for the preparation of various nanocomposites,whose appeal originates from the well-retained porous structures and exceptional electrochemical activities after thermal decomposition.This review focuses on the recent progress of PBA-derived nanocomposites from their fabrication,lithium/sodium/potassium storage mechanism,and applications in AIBs(LIBs,SIBs,and PIBs).To distinguish various PBA derivatives,the working mechanism and applications of PBA-templated metal oxides,metal chalcogenides,metal phosphides,and other nanocomposites are systematically evaluated,facilitating the establishment of a structure–activity correlation for these materials.Based on the fruitful achievements of PBA-derived nanocomposites,perspectives for their future development are envisioned,aiming to narrow down the gap between laboratory study and industrial reality.

Human leukocyte antigen and donor-specific antibodies in liver transplantation

In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.

Targeted gene sequencing and bioinformatics analysis of patients with gallbladder neuroendocrine carcinoma:A case report

BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alterations,mechanisms,and signaling pathways underlying gallbladder NEC remain unclear.CASE SUMMARY This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient,who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V.Targeted gene sequencing and bioinformatics analysis tools,including STRING,GeneMANIA,Metascape,TRRUST,Sangerbox,cBioPortal and GSCA,were used to analyze the biological functions and features of mutated genes in gallbladder NEC.Twelve mutations(APC,ARID2,IFNA6,KEAP1,RB1,SMAD4,TP53,BTK,GATA1,GNAS,and PRDM3)were identified,and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing.A protein-protein interaction network showed significant interactions among the twelve mutated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and pathways.The results revealed 40 tumor-related pathways.A key regulatory factor for gallbladder NEC-related genes was identified,and its biological functions and features were compared with those of gallbladder carcinoma.CONCLUSION Gallbladder NEC requires standardized treatment.Comparisons with other gallbladder carcinomas revealed clinical phenotypes,molecular alterations,functional characteristics,and enriched pathways.

Identification and Typing of Respiratory Adenoviruses in Guangzhou, Southern China Using a Rapid and Simple Method

Human adenoviruses (HAdVs), especially HAdV-B3, -E4 and -B7, are associated with Acute Respiratory Disease in Chinese children, and occasionally in adults. In order to establish and document the profiles of the respiratory adenovirus pathogen among children in Guangzhou, Southern China, a rapid, simple and practical method for identification and typing of respiratory adenoviruses was developed and evaluated. One pair of universal PCR primers was designed according to the conserved region of the hexon gene, which can detect not only HAdV-B3, -E4 and -B7, but also HAdV-B14, -F40 and -F41, with a specific 300bp PCR product. Three pairs of type-specific PCR primers were also designed according to the hypervariable regions of the hexon gene to type HAdV-B3, -E4 and -B7 by three independent PCR reactions, making it easy to optimize the PCR conditions. By using this method, one hundred throat swab specimens collected during Oct 2010 to Dec 2011 and suspected of being positive for adenoviral infection were identified and typed for adenoviruses. Of these samples, fifty-five were adenovirus-positive. The most common HAdV type was HAdV-B3, identified in 92.7% of samples, which is not only consistent with the data reported in 2004-2006, but also consistent with the recent report in Hangzhou, eastern China, indicating that HAdV-B3 has been circulating in Guangzhou, and maybe in eastern China, for many years. The method for the respiratory adenovirus identification and typing we developed is rapid, simple and practical, which has a potential in the real-time surveillance of circulating adenovirus strains and also to provide etiological evidence for the adenovirus-relative disease control and prevention in China.

Relationship between modified homeostasis model assessment/correlative serum factors and diabetic retinopathy among type 2 diabetics with insulin therapy in Guangzhou, China

AIM:To explore the related risk factors for diabetic retinopathy(DR)in type 2 diabetes with insulin therapy.METHODS:We studied the relationships among blood glucose,serum C-peptide,plasma insulin,beta-cell function and the development of DR.Beta-cell function was assessed by a modified homeostasis model assessment(modified HOMA)which was gained by using C-peptide to replace insulin in the homeostasis model assessment(HOMA)of beta-cell function.We also studied the relationships between modified HOMA index and serum C-peptide response to 100 g tasteless steamed bread to determine the accuracy of modified HOMA.RESULTS:Our study group consisted of 170 type 2diabetic inpatients with DR(age:58.35±13.87y,mean±SD)and 205 type 2 diabetic inpatients with no DR(NDR)(age:65.52±11.59y).DR patients had higher age,longer diabetic duration,higher hypertension grade,higher postprandial plasma glucose,higher fluctuation level of plasma glucose,lower body mass index(BMI),lower postprandial serum insulin and C-peptide,lower fluctuation level of serum insulin and C-peptide(P【0.05).In our logistic regression model,duration of diabetes,hypertension grade,fasting plasma insulin and glycosylated hemoglobin(HbA1C)were significantly associated with the presence of DR after adjustment for confounding factors(P【0.05).CONCLUSION:Our results suggested although modified HOMA showed significant correlation to the occurrence of DR on Spearman’s rank-correlationanalysis,logistic regression showed no significant association between these two variables after adjustment for relevant confounding factors(such as age,sex,duration of diabetes,BMI,hypertension grade,HbA1C,plasma insulin).Duration of diabetes,hypertension grade,fasting plasma insulin and HbA1C were independently associated with the development of DR in Chinese type 2 diabetics.

Prevalence and characteristics of peripheral myopic retinopathy in Guangzhou office workers

AIM： To determine the prevalence and characteristics of peripheral myopic retinopathy among a sample of Guangzhou office workers. METHODS： A cross-sectional study of Guangzhou Chinese office works in different departments and units of the Guangzhou Power Supply Bureau, China, in 2016. Myopic retinopathy was recorded and analyzed with a scanning laser ophthalmoscope and by slit-lamp microscopy combined with a three-mirror contact lens. RESULTS： In total, 1910 eyes of 955 subjects（508 females and 447 males） aged 21-59 y were included; 69.6% of these eyes were myopic. The myopia group had a younger age and worse uncorrected visual acuity（UCVA） and bestcorrected visual acuity（BCVA） when compared with hyperopia and emmetropia groups（P〈0.001）. The axial length（AL） was significantly longer, the spherical equivalent（SE） was more serious, and the optic nerve crescent was significantly larger in subjects with myopia than with hyperopia and emmetropia. Subjects with myopia, and especially high myopia, had the highest frequency of myopic retinal 18 changes（49.4%, P〈0.001） [white-without-pressure（43.8%, P〈0.001）, lattice degeneration（4.5%, P=0.044）] among the three groups. Logistic regression confirmed that any myopia（OR： 3.41, P〈0.001） [mild myopia（OR： 1.93, P=0.001）, moderate myopia（OR：3.64, P〈0.001）, and high myopia（OR：10.58, P〈0.001）], a greater AL（OR： 1.55, P〈0.001） and a much higher SE（OR： 0.77, P〈0.001） increased the risk for peripheral retinal changes.CONCLUSION： Myopia-related retinal changes are positively associated with greater AL, higher SE, and myopia.

One new species in the leaf-beetle genus Sphenoraia Clark(Coleoptera:Chrysomelidae:Galerucinae)from the Haizhu Wetland of Guangzhou,China

In this study,one new species of the leaf-beetle genus Sphenoraia Clark,1836(Coleoptera:Chrysomelidae:Galerucinae)is described from the Haizhu Wetland,Guangzhou,China:Sphenoraia(Sphenoraioides)haizhuensis Yang sp.nov.A key to the 12 Chinese species of Sphenoraia as well as photographs of the habitus and aedeagus of the new species and its related species are given.

Treatment results and prognostic analysis of 1093 primary nasopharyngeal carcinoma: the experience of a single institution of Guangzhou in the beginning of the 21st century

Objective： To analyze the treatment results of primary nasopharyngeal carcinoma （NPC） treated in our institution in the beginning of the 21st century to identify key failures and late effects for refining future treatments. Methods： 1093 patients with primary NPC treated during December 2001 and June 2003 were retrospectively analyzed. The distribution according to the AJCC/UICC （2002 edition） staging system was stage Ⅰ in 5.8%, stage Ⅱ 40.2%, stage Ⅲ 32.7% and stage Ⅳa-b 21.3%. Four different ERT techniques were used： fluoroscopy simulation conventional radiotherapy （CR） in 74.3% of patients, computer tomography simulation conventional radiotherapy （CT-sim CR） 14.2%, three-dimensional conformal radiotherapy （3D-CRT） 6.3%, intensity modulated radiotherapy （IMRT） 5.2%. In the whole series, 46.7% of patients had additional treatment with chemotherapy. Results： The 4-year local failure-free rate （LFFR）, nodal failure-free rate, distant metastasis-free rate, progression-free survival and overall survival （OS） was 89.6%, 96.1%, 85.9%, 73.0% and 82.4%, respectively. The stage was the most important prognostic factor. The 4-year OS and LFFR of patients treated by CR, CT-sim CR, 3D-CRT and IMRT was 80.2%, 89.8%, 89.8%, 92.4% and 87.7%, 96.4%, 91.0%, 96.5%, respectively. The morbidity and degree of xerostomia and trismus were lower in the patients treated by 3D-CRT and IMRT than by CR and CT-sim CR. Conclusion： Treatment results of primary NPC in our institution have been substantially improved. Distant metastasis is the main failure. The CT simulation and conformal radiotherapy can enhance the OS and LFFR, and conformal radiotherapy can reduce the morbidity and degree of late effects.

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Vibration-reduced anxiety-like behavior relies on ameliorating abnormalities of the somatosensory cortex and medial prefrontal cortex

Tibetan singing bowls emit low-frequency sounds and produce perceptible harmonic tones and vibrations through manual tapping.The sounds the singing bowls produce have been shown to enhance relaxation and reduce anxiety.However,the underlying mechanism remains unclear.In this study,we used chronic restraint stress or sleep deprivation to establish mouse models of anxiety that exhibit anxiety-like behaviors.We then supplied treatment with singing bowls in a bottomless cage placed on the top of a cushion.We found that unlike in humans,the combination of harmonic tones and vibrations did not improve anxietylike behaviors in mice,while individual vibration components did.Additionally,the vibration of singing bowls increased the level of N-methyl-D-aspartate receptor 1 in the somatosensory cortex and prefrontal cortex of the mice,decreased the level ofγ-aminobutyric acid A(GABA)receptorα1 subtype,reduced the level of CaMKII in the prefrontal cortex,and increased the number of GABAergic interneurons.At the same time,electrophysiological tests showed that the vibration of singing bowls significantly reduced the abnormal low-frequency gamma oscillation peak frequency in the medial prefrontal cortex caused by stress restraint pressure and sleep deprivation.Results from this study indicate that the vibration of singing bowls can alleviate anxiety-like behaviors by reducing abnormal molecular and electrophysiological events in somatosensory and medial prefrontal cortex.

Role of heterogenous microstructure and deformation behavior in achieving superior strength-ductility synergy in zinc fabricated via laser powder bed fusion

Zinc(Zn)is considered a promising biodegradable metal for implant applications due to its appropriate degradability and favorable osteogenesis properties.In this work,laser powder bed fusion(LPBF)additive manufacturing was employed to fabricate pure Zn with a heterogeneous microstructure and exceptional strength-ductility synergy.An optimized processing window of LPBF was established for printing Zn samples with relative densities greater than 99%using a laser power range of 80∼90 W and a scanning speed of 900 mm s−1.The Zn sample printed with a power of 80 W at a speed of 900 mm s−1 exhibited a hierarchical heterogeneous microstructure consisting of millimeter-scale molten pool boundaries,micrometer-scale bimodal grains,and nanometer-scale pre-existing dislocations,due to rapid cooling rates and significant thermal gradients formed in the molten pools.The printed sample exhibited the highest ductility of∼12.1%among all reported LPBF-printed pure Zn to date with appreciable ultimate tensile strength(∼128.7 MPa).Such superior strength-ductility synergy can be attributed to the presence of multiple deformation mechanisms that are primarily governed by heterogeneous deformation-induced hardening resulting from the alternative arrangement of bimodal Zn grains with pre-existing dislocations.Additionally,continuous strain hardening was facilitated through the interactions between deformation twins,grains and dislocations as strain accumulated,further contributing to the superior strength-ductility synergy.These findings provide valuable insights into the deformation behavior and mechanisms underlying exceptional mechanical properties of LPBF-printed Zn and its alloys for implant applications.

Fanlian Huazhuo Formula alleviates high-fat diet-induced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway

BACKGROUND Fanlian Huazhuo Formula(FLHZF)has the functions of invigorating spleen and resolving phlegm,clearing heat and purging turbidity.It has been identified to have therapeutic effects on type 2 diabetes mellitus(T2DM)in clinical application.Non-alcoholic fatty liver disease(NAFLD)is frequently diagnosed in patients with T2DM.However,the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation.AIM To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro.METHODS HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model.Subsequently,experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours.C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD,and then treated with the different concentrations of FLHZF for 10 weeks.RESULTS FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro.Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress,regulating the AMPKα/SREBP-1C signaling pathway,activating autophagy,and inhibiting hepatocyte apoptosis.CONCLUSION FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species,autophagy,apoptosis,and lipid synthesis signaling pathways,indicating its potential for clinical application in NAFLD.

Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.