Effects of reductive soil disinfestation on potential pathogens and antibiotic resistance genes in soil.

Reductive soil disinfestation (RSD) is commonly employed for soil remediation in greenhouse cultivation. However, its influence on antibiotic resistance genes (ARGs) in soil remains uncertain. This study investigated the dynamic changes in soil communities, potential bacterial pathogens, and ARG profiles under various organic material treatments during RSD, including distillers' grains, potato peel, peanut vine, and peanut vine combined with charcoal. Results revealed that applying diverse organic materials in RSD significantly altered bacterial community composition and diminished the relative abundance of potential bacterial pathogens (P < 0.05). The relative abundance of high-risk ARGs decreased by 10.7%-30.6% after RSD treatments, the main decreased ARG subtypes were AAC(3)_Via, dfrA1, ErmB, lnuB, aadA. Actinobacteria was the primary host of ARGs and was suppressed by RSD. Soil physicochemical properties, such as total nitrogen, soil pH, total carbon, were crucial factors affecting ARG profiles. Our findings demonstrated that RSD treatment inhibited pathogenic bacteria and could be an option for reducing high-risk ARG proliferation in soil.

Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model.

JOURNAL/nrgr/04.03/01300535-202503000-00030/figure1/v/2024-06-17T092413Z/r/image-tiff Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

Left Atrial Hemodynamics and Clinical Utility in Heart Failure.

Comprehensive knowledge of the left atrium (LA) and its pathophysiology has emerged as an important clinical and research focus in the heart failure (HF) arena. Although studies on HF focusing on investigating left ventricular remodeling are numerous, those on atrial structural and functional changes have received comparatively less attention. Studies on LA remodeling have recently received increasing attention, and LA pressure (LAP) has become a novel target for advanced monitoring and is a potential therapeutic approach for treating HF. Various devices specifically designed for the direct measurement of LAP have been developed to optimize HF treatment by reducing LAP. This review focuses on LA hemodynamic monitoring and effective LAP decompression.

Lateral column lengthening versus subtalar arthroereisis for pes planovalgus in patients with cerebral palsy: a systematic review and meta-analysis.

Introduction: Although pes planus, a common deformity in children with cerebral palsy (CP), is predominantly treated through lateral column lengthening (LCL), subtalar arthroereisis (SA) has also gained popularity for this purpose. This systematic review was conducted to compare surgical outcomes between LCL and SA for pes planovalgus in children with CP. Methods: PubMed, EMBASE, Cochrane Library, and Google Scholar were comprehensively searched for relevant articles reporting the outcomes of LCL and SA in the target population. Surgical outcomes were evaluated in terms of radiographic parameters and postoperative complications. Results: This review included 22 studies involving patients undergoing LCL (LCL group) and 9 studies involving those undergoing SA (SA group). LCL outperformed SA in terms of corrections in the talonavicular coverage angle (8.1°-42.1° vs. 8.0°-30.7°), anteroposterior talo-first metatarsal angle (12.3°-33.7° vs. 9.8°-21.4°), and calcaneal pitch angle (2.5°-29.7° vs. 3.5°-8.0°). Furthermore, the risk of postoperative complications, such as recurrence, pain, undercorrection, and overcorrection, was higher in the LCL group than in the SA group. However, the risks of reoperation and implant-related problems were higher in the SA group than in the LCL group. A meta-analysis of two randomized studies revealed that improvement in calcaneal pitch angle was significantly greater in the LCL group than in the SA group (mean difference: 2.09°; P = 0.0488). Conclusion: LCL outperforms SA in correcting pes planus-related radiographic parameters in patients with CP. However, postoperative complications appear to be more common after LCL than after SA. Systematic Review Registration: https://inplasy.com/inplasy-2024-5-0126, Identifier 202450126.

Antisolvent-assisted growth of inorganic CsPb(Br,I)3 under ambient conditions.

Controlling the growth of halide perovskite films under high relative humidity (RH) ambient conditions is significant for practical applications. Here, we control the antisolvent-assisted growth reactions with a constant temperature and low RH. With the hot casting setup and antisolvent during growth reactions, the synthesis of high coverage and pinhole-free CsPb(Br,I)3 films is achieved in ambient air.

The branched N-glycan of PD-L1 predicts immunotherapy responses in patients with recurrent/metastatic HNSCC.

Immunotherapy has revolutionized cancer treatment, but the lack of a reliable predictive biomarker for treatment response remains a challenge. Alpha-1,6-Mannosylglycoprotein 6-ß-N-Acetylglucosaminyltransferase 5 (MGAT5) is a key regulator of complex N-glycan synthesis, and its dysregulation is associated with cancer progression. The lectin Phaseolus vulgaris leukoagglutinin (PHA-L) specifically binds to mature MGAT5 products. Previous studies have indicated elevated PHA-L staining in head and neck squamous cell carcinoma (HNSCC), which implies increased activity of MGAT5. However, the specific role of MGAT5 in HNSCC remains unclear. In this study, we found significantly higher PHA-L staining and MGAT5 expression in HNSCC tumors compared to adjacent non-tumor tissues. Using a mass spectrometry (MS)-based glycoproteomic approach, we identified 163 potential protein substrates of MGAT5. Functional analysis revealed that protein substrates of MGAT5 regulated pathways related to T cell proliferation and activation. We further discovered that PD-L1 was among the protein substrates of MGAT5, and the expression of MGAT5 protected tumor cells from cytotoxic T lymphocyte (CTL) killing. Treatment of nivolumab alleviated the protective effects of MGAT5 on CTL activity. Consistently, patients with MGAT5-positive tumors showed improved responses to immunotherapy compared to those with MGAT5-negative tumors. Using purified PD-L1 from HNSCC cells and a glycoproteomic approach, we further deciphered that the N35 and N200 sites carry the majority of complex N-glycans on PD-L1. Our findings highlight the critical role of MGAT5-mediated branched N-glycans on PD-L1 in modulating the interaction with the immune checkpoint receptor PD-1. Consequently, we propose that MGAT5 could serve as a biomarker to predict patients' responses to anti-PD-1 therapy. Furthermore, targeting the branched N-glycans at N35 and N200 of PD-L1 may lead to the development of novel diagnostic and therapeutic approaches.

The epigenetic state of the cell of origin defines mechanisms of leukemogenesis.

Acute myeloid leukemia (AML) shows variable clinical outcome. The normal hematopoietic cell of origin impacts the clinical behavior of AML, with AML from hematopoietic stem cells (HSCs) prone to chemotherapy resistance in model systems. However, the mechanisms by which HSC programs are transmitted to AML are not known. Here, we introduce the leukemogenic MLL-AF9 translocation into defined human hematopoietic populations, finding that AML from HSCs is enriched for leukemic stem cells (LSCs) compared to AML from progenitors. By epigenetic profiling, we identify a putative inherited program from the normal HSC that collaborates with oncogene-driven programs to confer aggressive behavior in HSC-AML. We find that components of this program are required for HSC-AML growth and survival and identify RNA polymerase (RNAP) II-mediated transcription as a therapeutic vulnerability. Overall, we propose a mechanism as to how epigenetic programs from the leukemic cell of origin are inherited through transformation to impart the clinical heterogeneity of AML.

The efficacy and safety of continuous theta burst stimulation for auditory hallucinations: a systematic review and meta-analysis of randomized controlled trials.

Objective: Auditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia. Methods: We performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included "auditory hallucinations", "continuous theta burst stimulation" and "transcranial magnetic stimulation". Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data. Results: A total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented "low risk" in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD: -0.45 (95%CI: -1.01, 0.12), P = 0.13; I2 = 61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, -0.63), P = 0.02; I2 = 47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group. Conclusions: Although preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024534045.

Remodelling of the glycome of B-cell precursor acute lymphoblastic leukemia cells developing drug-tolerance.

Reduced responsiveness of precursor B-acute lymphoblastic leukemia (BCP-ALL) to chemotherapy can be first detected in the form of minimal residual disease leukemia cells that persist after 28 days of initial treatment. The ability of these cells to resist chemotherapy is partly due to the microenvironment of the bone marrow, which promotes leukemia cell growth and provides protection, particularly under these conditions of stress. It is unknown if and how the glycocalyx of such cells is remodelled during the development of tolerance to drug treatment, even though glycosylation is the most abundant cell surface post-translational modification present on the plasma membrane. To investigate this, we performed omics analysis of BCP-ALL cells that survived a 30-day vincristine chemotherapy treatment while in co-culture with bone marrow stromal cells. Proteomics showed decreased levels of some metabolic enzymes. Overall glycocalyx changes included a shift from Core-2 to less complex Core-1 O-glycans, and reduced overall sialylation, with a shift from α2-6 to α2-3 linked Neu5Ac. Interestingly, there was a clear increase in bisecting complex N-glycans with a concomitant increased mRNA expression of MGAT3 , the only enzyme known to form bisecting N-glycans. These small but reproducible quantitative differences suggest that individual glycoproteins become differentially glycosylated. Glycoproteomics confirmed glycosite-specific modulation of cell surface and lysosomal proteins in drug-tolerant BCP-ALL cells, including HLA-DRA, CD38, LAMP1 and PPT1. We conclude that drug-tolerant persister leukemia cells that grow under continuous chemotherapy stress have characteristic glycotraits that correlate with and perhaps contribute to their ability to survive and could be tested as neoantigens in drug-resistant leukemia.

Clinical Features and a Prediction Model for Early Prediction of Composite Outcome in Chlamydia psittaci Pneumonia: A Multi-Centre Retrospective Study in China.

Introduction: C. psittaci pneumonia has atypical clinical manifestations and is often ignored by clinicians. This study analyzed the clinical characteristics, explored the risk factors for composite outcome and established a prediction model for early prediction of composite outcome among C. psittaci pneumonia patients. Methods: A multicenter, retrospective, observational cohort study was conducted in ten Chinese tertiary hospitals. Patients diagnosed with C. psittaci pneumonia were included, and their clinical data were collected and analyzed. The composite outcome of C. psittaci pneumonia included death during hospitalization, ICU admission, and mechanical ventilation. Univariate and multivariable logistic regression analyses were conducted to determine the significant variables. A ten-fold cross-validation was performed to internally validate the model. The model performance was evaluated using various methods, including receiver operating characteristics (ROC), C-index, sensitivity, specificity, positive/negative predictive value (PPV/NPV), decision curve analysis (DCA), and clinical impact curve analysis (CICA). Results: In total, 83 patients comprised training cohorts and 36 patients comprised validation cohorts. CURB-65 was used to establish predictive Model 1. Multivariate logistic regression analysis identified three independent prognostic factors, including serum albumin, CURB-65, and white blood cells. These factors were employed to construct model 2. Model 2 had acceptable discrimination (AUC of 0.898 and 0.825 for the training and validation sets, respectively) and robust internal validity. The specificity, sensitivity, NPV, and PPV for predicting composite outcome in the nomogram model were 91.7%, 84.5%, 50.0%, and 98.4% in the training sets, and 100.0%, 64.7%, 14.2%, and 100.0% in the validation sets. DCA and CICA showed that the nomogram model was clinically practical. Conclusion: This study constructs a refined nomogram model for predicting the composite outcome in C. psittaci pneumonia patients. This nomogram model enables early and accurate C. psittaci pneumonia patients' evaluation, which may improve clinical outcomes.

Quantification of the interaction forces between dengue virus and dopamine type-2 receptor using optical tweezers.

BACKGROUND: Dengue virus (DENV) causes the most significant mosquito-borne viral disease with a wide spectrum of clinical manifestation, including neurological symptoms associated with lethal dengue diseases. Dopamine receptors are expressed in central nervous system, and dopamine antagonists have been reported to exhibit antiviral activity against DENV infection in vivo and in vitro. Although identification of host-cell receptor is critical to understand dengue neuropathogenesis and neurotropism, the involvement of dopamine receptors in DENV infection remains unclear. RESULTS: We exploited the sensitivity and precision of force spectroscopy to address whether dopamine type-2 receptors (D2R) directly interact with DENV particles at the first step of infection. Using optical tweezers, we quantified and characterized DENV binding to D2R expressed on Chinese hamster ovary (CHO) cells. Our finding suggested that the binding was D2R- and DENV-dependent, and that the binding force was in the range of 50-60 pN. We showed that dopamine antagonists prochlorperazine (PCZ) and trifluoperazine (TFP), previously reported to inhibit dengue infection, interrupt the DENV-D2R specific binding. CONCLUSIONS: This study demonstrates that D2R could specifically recognize DENV particles and function as an attachment factor on cell surfaces for DENV. We propose D2R as a host receptor for DENV and as a potential therapeutic target for anti-DENV drugs.

Clinical outcomes among patients with concurrent blunt cerebrovascular injury and traumatic intracranial hemorrhage.

BACKGROUND: Blunt cerebrovascular injury (BCVI) accounts for 1-3 % of patients with blunt trauma, which should be promptly diagnosed and managed due to risk of cerebral infarction and death. Antithrombotic therapy had been proven to reduce risk of stroke and mortality. However, due to concern of hematoma progression, treatment suggestion is still inconclusive for patients with concurrent traumatic intracranial hemorrhage. MATERIALS AND METHODS: We performed a retrospective, observational study from 2002 to 2020 at a Level I trauma center, all patients with BCVI and concurrent traumatic intracranial hemorrhage were recruited. Patients' demographics, initial CT findings, severity of BCVI, treatment and outcomes were documented and analyzed to define possible risk factors of death and stroke. RESULTS: Among all 57 patients, 49 (86.0 %) patients had injury at ICA, 6 (10.5 %) had VA injury, and 2 (3.5 %) suffered from both. Targeted treatments for BCVI were provided to 33 (57.9 %) patient, mostly endovascular intervention (78.8 %), antithrombotic treatment was given to 11 (19.3 %) patients. At 3-month follow-up, 17 (29.8 %) patients expired, and 18 (31.6 %) patients had cerebral infarction due to BCVI. We identified more severe initial CT findings (p = 0.016), higher head Abbreviated Injury Scale (p = 0.049) and initial life-threatening events (p = 0.047) as risk factors of death, and traumatic basal cistern subarachnoid hemorrhage(SAH) (p = 0.040) as single risk factor of cerebral infarction. CONCLUSIONS: Around one-thirds of patients with concurrent BCVI and traumatic intracranial hemorrhage were death or suffered from cerebral infarction within 3 months, with severity of initial head injury and SAH at basal cistern as risk factors, respectively.

Statin use associated with a reduced risk of hip fracture in patients with gout.

Studies show that statins users are at reduced risk of fracture and improved bone mineral density. However, the clinical effectiveness of statin use in patients with gout has not been investigated. This retrospective cohort study used data from Taiwan's National Health Insurance Research Database, consisting of 3443 patients with gout using statins aged 50 years and above and 6886 gout patients of non-statin users matched by sex, age and propensity score. The Cox proportional hazards regression analysis showed that statin use was associated with a reduced risk of hip fracture (adjusted hazard ratio [aHR] = 0.78, 95 % confidence interval [CI] = 0.64-0.94) after controlling for potential confounding factors. The association was significant in both genders aged 50-64 years, with aHRs of near 0.35, but not in the elderly. In addition, women aged 50-64 years who used statins also exhibited a lower risk of vertebral fracture (aHR = 0.70, 95 % CI = 0.50-0.99), but not men. In conclusion, the stating use in gout patients could reduce fracture risk for younger patients. Further research is warranted to confirm these findings.

Predictors of left ventricular outflow tract obstruction after biventricular repair in interrupted aortic arch or aortic coarctation.

BACKGROUND: Left ventricular outflow tract obstruction (LVOTO) re-intervention is a significant cause of morbidity and mortality in patients with coarctation of the aorta (CoA) or interrupted aortic arch (IAA) after aortoplasty. METHODS: This retrospective study analyzed data from neonates with IAA/CoA who underwent biventricular repair between 2012 and 2022. LVOTO events were defined by the detection of color Doppler flow acceleration ≥3.0 m/s at the valvular, subvalvular, or supravalvular regions via transthoracic echocardiography, and the necessity for surgical or catheter intervention to relieve the obstruction. RESULTS: Among 121 neonates with CoA/IAA, 16 (13.7%) primary aortoplasty patients developed LVOTO. Additionally, one patient (25%) who underwent a staged Yasui operation developed LVOTO due to a narrowed ventricular septal defect-pulmonary atresia tunnel. During follow-up, 58% of patients with a bicuspid valve and 25% of patients with a subaortic ridge developed LVOTO. The combination of either a bicuspid valve, subaortic ridge, or an aortic valve annulus Z-score < -3.0 predicted a high re-intervention rate (7/8 [87.5%]). CONCLUSIONS: In patients with IAA/CoA, the presence of multiple risk factors, including a bicuspid valve, subaortic ridge, and an aortic valve annulus Z-score < -3.0, is associated with a significantly increased rate of re-intervention for LVOTO.

Identification of triazolyl KAT6 inhibitors via a templated fragment approach.

KAT6, a histone acetyltransferase from the MYST family, has emerged as an attractive oncology target due to its role in regulating genes that control cell cycle progression and cellular senescence. Amplification of the KAT6A gene has been seen among patients with worse clinical outcome in ER+ breast cancers. Although multiple inhibitors have been reported, no KAT6 inhibitors have been approved to date. Here, we report the fragment-based discovery of a series of N-(1-phenyl-1H-1,2,3-triazol-4-yl)benzenesulfonamide KAT6 inhibitors and early hit-to-lead efforts to improve the KAT6 potency.

Plate osteosynthesis of phalanx fractures using wide-awake local anesthesia no tourniquet technique is cost-effective and associated with less postoperative pain.

BACKGROUND: The wide-awake local anesthesia no tourniquet (WALANT) technique, which is based on the local infiltration of lidocaine and epinephrine, is widely used in hand and wrist surgery. However, few studies have been conducted on the cost-benefit analysis of phalanx fracture surgery using the WALANT technique. This study aimed to investigate the clinical condition, time spent on anesthesia and operation. We also perform an economic analysis among general anesthesia, local anesthesia with a tourniquet, and the WALANT technique for plate fixation of phalanx fractures. METHODS: This retrospective study included all patients with single phalanx fractures who underwent open reduction internal fixation with plating between January 2015 and December 2019. Patients were divided into three groups according to the anesthesia method: general anesthesia with a tourniquet (GA group), local anesthesia with a tourniquet (LA group), and the WALANT technique (WALANT group). Data, including demographics, anesthesia and surgical time, postoperative pain score, and vomiting ratio, were collected and analyzed. RESULTS: A total of 62 patients were included in this study. Of the 62 patients, 15 were included in the GA group, 32 in the LA group, and 15 in the WALANT group. No complications were reported during surgery or follow-up in either group. The GA group exhibited a significantly longer anesthesia time than the other two groups, with an average of 32.4 min. However, no significant difference in surgical time was observed among the three groups. The WALANT group exhibited a significantly lower postoperative pain score than the other two groups. The additional cost of general anesthesia was approximately 350 US dollars (USD), accounting for approximately one-third to one-fourth of the total expenses for phalanx surgery. CONCLUSION: Open reduction with plate fixation of phalanx fractures using the WALANT technique and local anesthesia was cost-effective compared with general anesthesia. Patients who underwent phalanx fracture surgery using the WALANT technique experienced less pain on the first postoperative day than those who underwent surgery using general or local anesthesia with a tourniquet because of the adequate tumescent technique and not using a tourniquet during surgery.

Optimal two-stage arbitraging and scheduling strategy for distributed energy resource aggregators.

Given the rapid development of the distributed energy resources (DER), involving DERs into the wholesale market under the market and renewable uncertainties to achieve economic benefits is necessary but challenging. In this work, an arbitraging strategy is proposed for DER aggregators that bridge DERs with the wholesale market through energy trading. Besides, a novel self-adaptive minimax regret (MMR)-based optimal offering model is proposed for the DER aggregator to handle the uncertainties in both renewable generations and market prices. Additionally, an exact and communication-free solution methodology is proposed to resolve the formulated optimization problem with high computational efficiency. In the numerical results, the proposed methods can achieve near-to-optimal profits. Moreover, the performance of the proposed approach remains satisfactory even if the environment becomes very volatile.

Structural and molecular insights of two unique enzymes involved in the biosynthesis of a natural halogenated nitrile.

Organohalogen compounds exhibit wide-ranging bioactivities and potential applications. Understanding natural biosynthetic pathways and improving the production of halogenated compounds has garnered significant attention. Recently, the biosynthetic pathway of a cyanobacterial neurotoxin, aetokthonotoxin, was reported. It contains two unique enzymes: a single-component flavin-dependent halogenase AetF and a new type of nitril synthase AetD. The crystal structures of these enzymes in complex with their cofactors and substrates that were recently reported will be presented here. The AetF structures reveal a tri-domain architecture, the transfer direction of the hydride ion, a possible path to deliver the hypohalous acid, and the unusual bispecific substrate-recognition mode. The AetD structures demonstrate that the nitrile formation should occur through the action of a diiron cluster, implying that the enzyme should be capable of catalyzing the nitrile formation of alternative amino acids. This information is of central importance for understanding the mechanism of action as well as the applications of these two the-first-of-its-kind enzymes.

Nerve growth factor gene polymorphisms may be associated with heroin dependence in women but do not mediate specific personality traits.

Heroin dependence (HD) is a complex disease with a substantial genetic contribution and is associated with traits of impulsivity and specific personality traits. The neurotrophic factor nerve growth factor (NGF) may mediate the reward processes in HD. This study aims to investigate whether NGF gene polymorphisms are associated with the co-occurrence of HD and impulsivity/specific personality traits in HD patients. To minimize the potential confounding effects of population stratification, we selected a homogeneous Han Chinese population and recruited 1364 participants (831 HD patients and 533 healthy controls). In addition, 163 female HD patients completed the Chinese version of the Barratt Impulsiveness Scale Version 11 (BIS-11), and 440 HD patients completed the Chinese version of the Tridimensional Personality Questionnaire (TPQ) for subsequent analysis. We identified three polymorphisms with altered allele and genotype frequency in HD patients versus controls (p = 0.035 for rs2254527; p = 0.005 for rs6678788; p = 0.006 for rs7523654), especially in the female subgroup. Four associations identified via haplotype analysis were significant in the female subgroup (p = 0.003 for T-T-A haplotype and p = 0.002 for C-C-A haplotype in block 1; p = 0.011 for T-T haplotype and p = 0.009 for C-T haplotypes in block 2), but not in the male subgroup. Male HD patients had higher novelty-seeking (NS) scores, and female HD patients had higher harm avoidance (HA) scores. However, there was no significant association between the selected NGF polymorphisms and BIS or TPQ scores in HD patients. NGF variants may contribute to the risk of HD development in females but do not mediate the relationship between impulsivity and specific personality traits in the female population.

Enhancing ocular protection against UVB: The role of irigenin in modulating oxidative stress and apoptotic pathways In Vivo.

Oxidative damage contributes to age-related macular degeneration. Irigenin possesses diverse pharmacologic properties, including antioxidative and antiapoptotic effects. Our in vivo experiments indicated that irigenin mitigates UVB-induced histopathologic changes and oxidative DNA damage. Histologic analyses and TUNEL staining revealed that this compound dose-dependently ameliorated UVB-induced retinal damage and apoptosis. Furthermore, irigenin substantially reduced the level of 8-hydroxyguanosine, a biomarker of UVB-induced oxidative DNA damage. We further explored the molecular mechanisms that mediate the protective effects of irigenin. Our findings suggested that UVB-induced generation of ROS disrupts the stability of the mitochondrial membrane, activating intrinsic apoptotic pathways; the underlying mechanisms include the release of cytochrome c, activation of caspase-9 and caspase-3, and subsequent degradation of PARP-1. Notably, irigenin reversed mitochondrial disruption and apoptosis. It also modulated the Bax and Bcl-2 expression but influenced the mitochondrial apoptotic pathways. Our study highlights the role of the Nrf2 pathway in mitigating the effects of oxidative stress. We found that UVB exposure downregulated, but irigenin treatment upregulated the expression of Nrf2 and antioxidant enzymes. Therefore, irigenin activates the Nrf2 pathway to address oxidative stress. In conclusion, irigenin exhibits protective effects against UVB-induced ocular damage, evidenced by the diminution of histological alterations. It mitigates oxidative DNA damage and apoptosis in the retinal tissues by modulating the intrinsic apoptotic pathways and the AIF mechanisms. Furthermore, irigenin effectively reduces lipid peroxidation, enhancing the activity of antioxidant enzymes by stimulating the Nrf2 pathway. This protective mechanism underscores the potential benefit of irigenin in combating UVB-mediated ocular damage.