The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

BACKGROUND: Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021. METHODS: Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index. RESULTS: In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates. CONCLUSIONS Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.
Humans ; Global Burden of Disease ; Male ; Female ; Middle Aged ; Adult ; Asia/epidemiology* ; Prevalence ; Aged ; Pulmonary Arterial Hypertension/mortality* ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Hypertension, Pulmonary/epidemiology*

Objective This study sought to accelerate the establishment of a Parkinson's disease mouse model by intracerebral injection of α-synuclein preformed fibrils(α-Syn PFF)into B6-hSNCA-A53T transgenic mice to induce rapid development of Parkinson's-like pathological features.Methods C57BL/6J background α-Syn A53T transgenic mice were selected as the model group,with isogenic C57BL/6J mice as the control group.α-Syn PFF was delivered into the bilateral striatum using stereotactic brain injection.After modeling,the open-field test was used to assess spontaneous activity and anxiety-like behaviors,while the rotarod,grip strength,and pole tests evaluated motor coordination and limb muscle tone.The buried food test was conducted to assess olfactory function.Immunohistochemical staining was performed to investigate neuroinflammation and pathological α-synuclein in the mouse brain.Results Compared with the control group,1 month after the α-Syn PFF injection,model mice showed increased locomotion in the open-field test,with no significant differences in the rotarod,grip strength,or pole tests,but prolonged food-seeking time.Two months after model establishment,the model group showed significantly reduced locomotor activity in open field testing,impaired motor coordination in rotarod,grip strength and pole tests,and olfactory dysfunction in buried food tests.Phosphorylated α-synuclein accumulation was observed in the substantia nigra,cortex,and hippocampus,accompanied by pronounced microglial activation,Lewy body deposition,and substantial dopaminergic neuron loss in the substantia nigra.Conclusions A53T mice developed olfactory dysfunction and motor impairments more rapidly after α-Syn PFF injection.Significant pathological changes were observed,including the aggregation of α-synuclein/Lewy body in the substantia nigra,cortex,and hippocampus,and the loss of dopaminergic neurons in the substantia nigra.This model can serve as a rapidly established animal model for α-synucleinopathy-related Parkinson's disease.

Objective This study sought to accelerate the establishment of a Parkinson's disease mouse model by intracerebral injection of α-synuclein preformed fibrils(α-Syn PFF)into B6-hSNCA-A53T transgenic mice to induce rapid development of Parkinson's-like pathological features.Methods C57BL/6J background α-Syn A53T transgenic mice were selected as the model group,with isogenic C57BL/6J mice as the control group.α-Syn PFF was delivered into the bilateral striatum using stereotactic brain injection.After modeling,the open-field test was used to assess spontaneous activity and anxiety-like behaviors,while the rotarod,grip strength,and pole tests evaluated motor coordination and limb muscle tone.The buried food test was conducted to assess olfactory function.Immunohistochemical staining was performed to investigate neuroinflammation and pathological α-synuclein in the mouse brain.Results Compared with the control group,1 month after the α-Syn PFF injection,model mice showed increased locomotion in the open-field test,with no significant differences in the rotarod,grip strength,or pole tests,but prolonged food-seeking time.Two months after model establishment,the model group showed significantly reduced locomotor activity in open field testing,impaired motor coordination in rotarod,grip strength and pole tests,and olfactory dysfunction in buried food tests.Phosphorylated α-synuclein accumulation was observed in the substantia nigra,cortex,and hippocampus,accompanied by pronounced microglial activation,Lewy body deposition,and substantial dopaminergic neuron loss in the substantia nigra.Conclusions A53T mice developed olfactory dysfunction and motor impairments more rapidly after α-Syn PFF injection.Significant pathological changes were observed,including the aggregation of α-synuclein/Lewy body in the substantia nigra,cortex,and hippocampus,and the loss of dopaminergic neurons in the substantia nigra.This model can serve as a rapidly established animal model for α-synucleinopathy-related Parkinson's disease.

The relationship between the duration of type 2 diabetes mellitus (T2DM) and the risk of female reproductive malignancies is complex and multifaceted. Large population cohort studies revealed a negative association between the duration of T2DM and the incidence of breast cancer and endometrial cancer. Furthermore, the risk of breast and endometrial cancer is the highest within a short time after T2DM diagnosis and remains remarkably higher in patients with longer diabetes duration than in the nondiabetic population. This phenomenon suggests causal reverse bias and potential detection bias. Nevertheless, T2DM remains an important risk factor for breast and endometrial cancer. Research on the association between diabetes with cervical and ovarian cancer is limited, and results vary by region. Future epidemiological studies should focus on large prospective studies with long follow-up to further investigate this association. Research into the biological mechanisms linking diabetes and female reproductive cancers is also necessary to develop effective cancer prevention and early intervention strategies.

ObjectiveTo study the genetic diversity and genetic relationship of Pinellia ternata germplasm resources and provide the basis for germplasm identification， variety breeding， and resource conservation. MethodIn this study， 27 P. ternata were used as experimental materials to determine seven phenotypic characters， such as plant height， leaf length， and leaf width. Simple sequence repeats （SSR） primers were designed based on P. ternata transcriptome data， and polymerase chain reaction （PCR） amplification was performed on 27 P. ternata samples. The genetic diversity of P. ternata germplasm was analyzed by POPGENE32， PowerMarker V3.25， and NTSYS-PC 2.10e software. ResultA total of 10 pairs of highly polymorphic primers （PIC>0.5） and four pairs of moderately polymorphic primers （0.25

Objective:To explore the genetic basis for a fetus featuring oligodactyly.Methods:A fetus with hand deformity identified by ultrasound at the Maternal and Child Health Care Hospital of Hubei Province on October 20, 2018 was selected as the study subject. Clinical information and ultrasonographic finding of the pregnant woman were collected. Following elected abortion, umbilical cord and peripheral venous blood samples of the couple were collected for the extraction of genomic DNA. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out. Candidate variants were verified by Sanger sequencing.Results:Ultrasonographic examination at 30 + 2 weeks of gestation revealed that the fetus had small right hand with absence of 2nd ~ 5th fingers, whilst its left hand had appeared to be normal. By CNV-seq, no pathogenic or likely pathogenic copy number variation (CNV) (> 100 kb) was detected in the fetus. Trio-WES revealed that the fetus had harbored a novel heterozygous c.3298G>A (p.Val1100Met) variant of the SMC3 gene. The variant has not been recorded in the population databases, and was predicted to be deleterious by several bioinformatics software and evolutionarily conserved based on multiple sequence alignment analysis. Sanger sequencing showed that neither parent has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3). Conclusion:The fetus was diagnosed with Cornelia de Lange syndrome, for which the novel heterozygous c.3298G>A variant of the SMC3 gene may be accountable.

Objective To explore whether voluntary wheel running affects liver oxidative stress by regulating the Nrf2/HO-1 pathway,thereby alleviating HFFC diet-related lipid deposition in the liver.Methods Eight-week-old C57BL/6J mice were randomly divided into a normal diet group(NC group,n=10)and high-fat,fructose,and cholesterol diet group(HFFC group,n=20)after 1 week of adaptive feeding.Ten weeks of feeding later,mice in the HFFC group were divided into a quiet group(HFFC group,n=10)and HFFC combined with exercise group(HFFC+EX group,n=10).HFFC+EX group mice were caged with voluntary running wheels for free movement,and the number of running wheels was recorded every day for 8 weeks.After the last treatment,the mice were sacrificed by fasting for 12 hours at an interval of 24 hours,and the blood and liver were collected for analysis.Results(1)Body weight,liver weight,and liver index of mice fed the HFFC diet were significantly higher than those of the NC group,which significantly decreased after exercise(P＜0.05).(2)Compared with the NC group,HDL-C and LDL-C in the HFFC group were significantly increased,and the LDL-C level was significantly decreased after 8 weeks of exercise(P＜0.05).(3)The liver fat droplet area and liver TG content in the HFFC group were significantly higher than those in the NC group,whereas those in HFFC+EX group were significantly decreased(P＜0.05).(4)Compared with the NC group,the content of oxidase MDA in the HFFC group were significantly increased,and nuclear translocation and gene expression of Nrf2 were significantly decreased.After exercise,the activities of SOD and T-AOC were significantly increased,and the nuclear translocation and gene expression of Nrf2 and expression levels of HO-1 and SOD-1 were significantly increased(P＜0.05).(5)The number of apoptotic hepatocytes and CHOP expression in the HFFC diet group were significantly higher than those in the NC group,whereas the number of apoptotic hepatocytes,and CHOP and Bax/Bcl-2 expression in the exercise group were significantly lower than those in the NC group(P＜0.05).Conclusions Voluntary wheel can alleviate HFFC diet induced liver lipid deposition by regulating the Nrf2/HO-1 pathway,thereby alleviating oxidative stress and reducing apoptosis in liver cells.

Objective:To analyze the factors influencing sarcopenia in older patients with chronic diseases, both in community settings and hospitals, and to develop a risk prediction model for sarcopenia.Methods:We recruited a total of 403 older adults with chronic diseases, consisting of 251 individuals from a community in Nanjing, Jiangsu Province, and 152 hospitalized patients from the Department of Geriatrics at Jiangsu Province Hospital.Assessments were conducted using a general information questionnaire, serum sample collection, the mini nutritional assessment-short form(MNA-SF), the mini-mental state examination(MMSE), and the geriatric depression scale(GDS).Binary Logistic regression analysis was employed to identify influencing factors and to construct a risk prediction model for sarcopenia, which was illustrated using a nomogram.The model's discrimination was evaluated using the receiver operating characteristic(ROC)curve and the area under the curve(AUC).Results:The prevalence of sarcopenia among community-dwelling older adults with chronic conditions was found to be 4.0%(10/251).In contrast, the prevalence in hospitalized older adults with chronic conditions was significantly higher at 36.2%(55/152).Binary Logistic regression analysis identified several independent risk factors for sarcopenia, including hospitalization( OR=14.391、95% CI: 6.284-32.955、 P<0.001), male gender( OR=3.321、95% CI: 1.587-6.950、 P=0.001), lower low-density lipoprotein cholesterol(LDL-C)levels( OR=2.542、95% CI: 1.160-5.572、 P=0.020), cognitive impairment( OR=2.654、95% CI: 1.269-5.550、 P=0.010), and the use of four or more types of medication( OR=2.328、95% CI: 1.952-5.689、 P=0.044).Based on these risk factors, a nomogram was developed as a predictive model for assessing sarcopenia risk.The AUC for this prediction model was 0.860(95% CI: 0.815-0.912), indicating a sensitivity of 0.831 and a specificity of 0.760. Conclusions:The incidence of sarcopenia is notably high among older patients with chronic diseases.A risk prediction model that incorporates factors such as hospitalization history, gender, LDL-C levels, cognitive function, and types of medication demonstrates significant potential for predicting sarcopenia.This model serves as a valuable foundation for the early screening and intervention of sarcopenia.

Objective To investigate the effects of Jianpi Yichang Powder on regulating the NLRP3 inflammasome signaling pathway to inhibit dendritic cells(DCs)inflammatory injury induced by TNF-α;To explore its mechanism in the treatment of ulcerative colitis.Methods C57BL/6 mice DCs were primitively isolated and cultured.The cultured DCs were randomly divided into the normal group,model group,negative control group,positive drug group and TCM group.DCs inflammatory microenvironment model was established by TNF-α induction.After corresponding treatments were given to each group,CCK-8 method was used to detect cell proliferation ability,immunofluorescence and Western blot were used to detect the protein expressions of NLRP3,ASC and Caspase-1 in DCs respectively,Western blot and RT-PCR were used to detect the protein and mRNA expressions of IL-1β and IL-18 in DCs.Results Compared with the normal group,the proliferation ability in DCs of model group significantly decreased(P<0.01),the positive expressions of NLRP3,ASC and Caspase-1 significantly increased,the expressions of NLRP3,ASC,Caspase-1,IL-18,IL-1β protein and IL-18,IL-1β mRNA in DCs significantly increased(P<0.01).Compared with the model group and negative control group,the proliferation ability of DCs significantly increased in positive drug group and TCM group(P<0.01),the positive expressions of NLRP3,ASC,and Caspase-1 significantly decreased(P<0.01),the protein expressions of NLRP3,ASC,Caspase-1,IL-1β and IL-18 significantly decreased(P<0.05,P<0.01),and the mRNA expressions of IL-1β and IL-18 significantly decreased(P<0.01).The cell proliferation ability,Caspase-1 positive expression,and IL-18 mRNA expression of TCM group were significantly higher than those of the positive drug group(P<0.05),while the mRNA expression of IL-1β was lower than that of the positive drug group(P<0.05).Conclusion Jianpi Yichang Powder can inhibit the inflammatory response of DCs induced by TNF-α,and its mechanism in the treatment of ulcerative colitis may be related to regulating the expressions of the NLRP3 inflammasome signaling pathway,including the expressions of NLRP3,ASC,Caspase-1,IL-18 and IL-1β.