Differences in neuroinflammation in people who started antiretroviral treatment during primary versus chronic HIV infection: an 18kDa Translocator protein (TSPO) positron emission tomography (PET) study.

Persistent inflammation is described in people with HIV (PWH) on antiretroviral treatment (ART). Early ART initiation is associated with reduced inflammation. We aimed to evaluate neuroinflammation, using translocator protein (TSPO) [11C]PBR28 PET neuroimaging in PWH who initiated ART during acute HIV (aPWH) versus chronic HIV infection (cPWH) versus a control population. This was a cross-sectional, observational study. All participants underwent [11C]PBR28 PET-CT neuroimaging. Using a two-tissue compartment model, total volume of distribution (VT) and distribution volume ratios (DVR) using cortical grey matter as a pseudo-reference region at 20 regions of interest (ROIs) were calculated. Differences in VT and DVR were compared between groups using the Kruskall-Wallis test. Seventeen neuro-asymptomatic male PWH on ART (9 aPWH, 8 cPWH) and 8 male control participants (CPs) were included. Median (interquartile range, IQR) age was 40 (30, 46), 44 (41, 47) and 21 (20, 25) years in aPWH, cPWH and CPs, respectively. Median (IQR) CD4 (cells/µL) and CD4:CD8 were 687 (652, 1014) and 1.37 (1.24, 1.42), and 700 (500, 720) and 0.67 (0.64, 0.82) in aPWH and cPWH, respectively. Overall, no significant difference in VT and DVR were observed between the three groups at any ROIs. cPWH demonstrated a trend towards higher mean VT compared with aPWH and CPs at most ROIs. No significant differences in neuroinflammation, using [11C]PBR28 binding as a proxy, were identified between cPWH, aPWH and CPs. A trend towards lower absolute [11C]PBR28 binding was seen amongst aPWH and CPs, suggesting early ART may mitigate neuroinflammation.

Epileptic brain network mechanisms and neuroimaging techniques for the brain network.

Epilepsy can be defined as a dysfunction of the brain network, and each type of epilepsy involves different brain-network changes that are implicated differently in the control and propagation of interictal or ictal discharges. Gaining more detailed information on brain network alterations can help us to further understand the mechanisms of epilepsy and pave the way for brain network-based precise therapeutic approaches in clinical practice. An increasing number of advanced neuroimaging techniques and electrophysiological techniques such as diffusion tensor imaging-based fiber tractography, diffusion kurtosis imaging-based fiber tractography, fiber ball imaging-based tractography, electroencephalography, functional magnetic resonance imaging, magnetoencephalography, positron emission tomography, molecular imaging, and functional ultrasound imaging have been extensively used to delineate epileptic networks. In this review, we summarize the relevant neuroimaging and neuroelectrophysiological techniques for assessing structural and functional brain networks in patients with epilepsy, and extensively analyze the imaging mechanisms, advantages, limitations, and clinical application ranges of each technique. A greater focus on emerging advanced technologies, new data analysis software, a combination of multiple techniques, and the construction of personalized virtual epilepsy models can provide a theoretical basis to better understand the brain network mechanisms of epilepsy and make surgical decisions.

ER-tethered RNA-binding protein controls NADPH oxidase translation for hydrogen peroxide homeostasis.

Hydrogen peroxide (H2O2) functions as a signaling molecule in diverse cellular processes. While cells have evolved the capability to detect and manage changes in H2O2 levels, the mechanisms regulating key H2O2-producing enzymes to maintain optimal levels, especially in pancreatic beta cells with notably weak antioxidative defense, remain unclear. We found that the protein EI24 responds to changes in H2O2 concentration and regulates the production of H2O2 by controlling the translation of NOX4, an enzyme that is constitutively active, achieved by recruiting an RNA-binding protein, RTRAF, to the 3'-UTR of Nox4. Depleting EI24 results in RTRAF relocating into the nucleus, releasing the brake on NOX4 translation. The excessive production of H2O2 by liberated NOX4 further suppresses the translation of the key transcription factor MafA, ultimately preventing its binding to the Ins2 gene promoter and subsequent transcription of insulin. Treatment with a specific NOX4 inhibitor or the antioxidant NAC reversed these effects and alleviated the diabetic symptoms in beta-cell specific Ei24-KO mice. This study revealed a new mechanism through which cells regulate oxidative stress at the translational level, involving an ER-tethered RNA-binding protein that controls the expression of the key H2O2-producing enzyme NOX4.

Effect of cytochrome P450 2C19 (CYP2C19) gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI.

Objective: To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with long-term clinical outcome in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). Methods: In total, 675 patients were enrolled. Based on the platelet inhibition rate, patients were categorized into two groups: clopidogrel low responsiveness (CLR) and normal clopidogrel responsiveness (NCR). The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment. Patients were classified into three groups (normal metabolizer, intermediate metabolizer, and poor metabolizer) based on the CYP2C19 genotype. We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity. The cumulative rates of 12-month all-cause deaths, major adverse cardiovascular events (MACCEs), and bleeding events were calculated. Results: CLR was observed in 44.4% of the overall population. Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes (P < 0.05). At the 12-month follow-up, 13 patients (1.9%) died and 96 patients (14.2%) experienced MACCEs. Patients with CLR (9.6% vs. 11.7% vs. 22.1%, P < 0.05) or poor metabolizer (10.7% vs. 16.4% vs. 22.6%, P = 0.026) experienced a higher rate of MACCEs. A MACCEs risk score between zero and two was calculated. The highest incidence of MACCEs significantly increased with the 2-positive results, and the area under the curve (AUC) was 0.712 (95% CI: 0.650-0.774, P < 0.05). There was no significant difference between the group with a score of one and the occurrence of MACCEs (P > 0.05). Conclusions: Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism. CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI, which is better than either test alone.

A comprehensive biomechanical evaluation of length and diameter of dental implants using finite element analyses: A systematic review.

Background: With a wide range of dental implants currently used in clinical scenarios, evidence is limited on selecting the type of dental implant best suited to endure the biting force of missing teeth. Finite Element Analysis (FEA) is a reliable technology which has been applied in dental implantology to study the distribution of biomechanical stress within the bone and dental implants. Purpose: This study aimed to perform a systematic review to evaluate the biomechanical properties of dental implants regarding their length and diameter using FEA. Material and methods: A comprehensive search was performed in PubMed/MEDLINE, Scopus, Embase, and Web of Science for peer-reviewed studies published in English from October 2003 to October 2023. Data were organized based on the following topics: area, bone layers, type of bone, design of implant, implant material, diameter of implant, length of implant, stress units, type of loading, experimental validation, convergence analysis, boundary conditions, parts of Finite Element Model, stability factor, study variables, and main findings. The present study is registered in PROSPERO under number CRD42022382211. Results: The query yielded 852 results, of which 40 studies met the inclusion criteria and were selected in this study. The diameter and length of the dental implants were found to significantly influence the stress distribution in cortical and cancellous bone, respectively. Implant diameter was identified as a key factor in minimizing peri-implant stress concentrations and avoiding crestal overloading. In terms of stress reduction, implant length becomes increasingly important as bone density decreases. Conclusions: The diameter of dental implants is more important than implant length in reducing bone stress distribution and improving implant stability under both static and immediate loading conditions. Short implants with a larger diameter were found to generate lower stresses than longer implants with a smaller diameter. Other potential influential design factors including implant system, cantilever length, thread features, and abutment collar height should also be considered in future implant design as they may also have an impact on implant performance.

Efficacy and Safety of High-Voltage Pulsed Radiofrequency versus Standard-Voltage Pulsed Radiofrequency for Patients with Neuropathic Pain: A Literature Review and Meta-Analysis.

Background: Neuropathic pain (NP) is recognized as one of the most difficult pain syndromes which lacks a safe, well-tolerated and effective treatment. Pulsed radiofrequency (PRF), a novel and minimally invasive interventions, has been introduced to alleviate various types of NP. Previous studies reported PRF with higher voltage could further improve the treatment efficacy. Therefore, we conducted this systematic review and meta-analysis to determine whether high-voltage PRF is superior to standard-voltage PRF for the treatment of NP patients. Methods: Databases published from the date of inception until 15 March 2022 on PubMed/MEDLINE, EMBASE, Web of Science and the Cochrane Library were searched for RCTs comparing high-voltage PRF and standard-voltage PRF in NP patients. The primary outcome measures were the efficiency rates of NP patients with high-voltage PRF or standard-voltage PRF treatment. Data analysis was conducted using the Review Manager software (RevMan V.5.3). Results: Six RCTs involving 423 patients were included in our meta-analysis. Compared with standard-voltage PRF group, the high-voltage PRF group attained a higher efficiency rate at 1 month (P = 0.04; I2 = 0%), 3 months (P = 0.04; I2 = 0%), 6 months (P = 0.002; I2 = 0%) post-procedure respectively. There was no significant difference in the complications between the two groups. Conclusion: Our study supported that high-voltage PRF attained more satisfactory efficacy than standard-voltage PRF without increased side effects. High-voltage PRF could be a promising, effective, minimally invasive technology for NP patients.

Nanotechnology-based optical sensors for Baijiu quality and safety control.

Baijiu quality and safety have received considerable attention owing to the gradual increase in its consumption. However, owing to the unique and complex process of Baijiu production, issues leading to quality and safety concerns may occur during the manufacturing process. Therefore, establishing appropriate analytical methods is necessary for Baijiu quality assurance and process control. Nanomaterial (NM)-based optical sensing techniques have garnered widespread interest because of their unique advantages. However, comprehensive studies on nano-optical sensing technology for quality and safety control of Baijiu are lacking. In this review, we systematically summarize NM-based optical sensor applications for the accurate detection and quantification of analytes closely related to Baijiu quality and safety. Furthermore, we evaluate the sensing mechanisms for each application. Finally, we discuss the challenges nanotechnology poses for Baijiu analysis and future trends. Overall, nanotechnological approaches provide a potentially useful alternative for simplifying Baijiu analysis and improving final product quality and safety.

Unveiling the Role of Fluorination in Hexacyclic Coordinated Ether Electrolytes for High-Voltage Lithium Metal Batteries.

Fluorinated ethers have become promising electrolyte solvent candidates for lithium metal batteries (LMBs) because they are endowed with high oxidative stability and high Coulombic efficiencies of lithium metal stripping/plating. Up to now, most reported fluorinated ether electrolytes are -CF3-based, and the influence of ion solvation in modifying degree of fluorination has not been well-elucidated. In this work, we synthesize a hexacyclic coordinated ether (1-methoxy-3-ethoxypropane, EMP) and its fluorinated ether counterparts with -CH2F (F1EMP), -CHF2 (F2EMP), or -CF3 (F3EMP) as terminal group. With lithium bis(fluorosulfonyl)imide as single salt, the solvation structure, Li-ion transport behavior, lithium deposition kinetics, and high-voltage stability of the electrolytes were systematically studied. Theoretical calculations and spectra reveal the gradually reduced solvating power from nonfluorinated EMP to fully fluorinated F3EMP, which leads to decreased ionic conductivity. In contrast, the weakly solvating fluorinated ethers possess higher Li+ transference number and exchange current density. Overall, partially fluorinated -CHF2 is demonstrated as the desired group. Further full cell testing using high-voltage (4.4 V) and high-loading (3.885 mAh cm-2) LiNi0.8Co0.1Mn0.1O2 cathode demonstrates that F2EMP electrolyte enables 80% capacity retention after 168 cycles under limited Li (50 µm) and lean electrolyte (5 mL Ah-1) conditions and 129 cycles under extremely lean electrolyte (1.8 mL Ah-1) and the anode-free conditions. This work deepens the fundamental understanding on the ion transport and interphase dynamics under various degrees of fluorination and provides a feasible approach toward the design of fluorinated ether electrolytes for practical high-voltage LMBs.

ERCP endoscopic minimally invasive treatment of acute suppurative obstructive cholangitis: A study of 47 patients.

The primary objective of the present study was to investigate the efficacy and safety of endoscopic therapy for acute obstructive suppurative cholangitis (AOSC) in patients with different underlying conditions. The present study comprised 47 patients diagnosed with AOSC, with a mean age of 70±14 years. Minimally invasive endoscopic treatments, including endoscopic duodenal papillary sphincterotomy, endoscopic duodenal nasobiliary drainage and/or placement of an endobiliary duct stent drainage tube, were performed. Variations in the levels of the white blood cell count, liver function, procalcitonin (PCT) and carbohydrate antigen-199 (CA199) were examined, compared and evaluated both prior to and following endoscopic retrograde cholangiopancreatography (ERCP). Among the 47 patients, 45 had a high fever, although their body temperature returned to normal after 7 days of ERCP treatment. The infection was difficult to control completely in two cases, including one case of biliary anastomosis secondary tumor with stenosis and AOSC and another case of an elderly patient with multiple choledocholithiasis complicated with sepsis. Within 7 days following treatment, the abdominal pain was resolved in 27 patients and jaundice subsided in 29 patients. On the 7th day after endoscopic treatment, the blood leukocyte, liver function, PCT and CA-199 parameters of all patients were significantly improved compared with those at admission. A total of 35 bile cultures yielded positive results, with Escherichia coli accounting for 11 cases (31.4%), Klebsiella pneumoniae accounting for 7 cases (20%), Pseudomonas aeruginosa accounting for 5 cases (14.3%), Enterococcus faecus accounting for 4 cases (11.4%) and other strains making up the remaining 17 cases. No serious complications were encountered with these patients, such as perforation, bleeding, severe pancreatitis or mortality, following ERCP. In conclusion, ERCP has been shown to be a safe and effective minimally invasive treatment method for elderly patients with AOSC, yielding a high rate of success.

Chemical and genetic basis of orange flavor.

Sweet orange (Citrus sinensis) exhibits limited genetic diversity and high susceptibility to Huanglongbing (HLB). Breeding HLB-tolerant orange-like hybrids is in dire need. However, our understanding of the key compounds responsible for orange flavor and their genetic regulation remains elusive. Evaluating 179 juice samples, including oranges, mandarins, Poncirus trifoliata, and hybrids, distinct volatile compositions were found. A random forest model predicted untrained samples with 78% accuracy and identified 26 compounds crucial for orange flavor. Notably, seven esters differentiated orange from mandarin flavor. Cluster analysis showed six esters with shared genetic control. Differential gene expression analysis identified C. sinensis alcohol acyltransferase 1 (CsAAT1) responsible for ester production in orange. Its activity was validated through overexpression assays. Phylogeny revealed the functional allele was inherited from pummelo. A SNP-based DNA marker in the coding region accurately predicted phenotypes. This study enhances our understanding of orange flavor compounds and their biosynthetic pathways and expands breeding options for orange-like cultivars.

Strawberry soluble solids QTL with inverse effects on yield.

Sugars are the main drivers of strawberry sweetness, and understanding their genetic control is of critical importance for breeding. Large-scale genome-wide association studies were performed in two populations totaling 3399 individuals evaluated for soluble solids content (SSC) and fruit yield. Two stable quantitative trait loci (QTL) on chromosome 3B and 6A for SSC were identified. Favorable haplotypes at both QTL for SSC decreased yield, though optimal allelic combinations were identified with reduced impacts on yield. Metabolites in the starch and sucrose metabolism pathway were characterized and quantified for 23 contrasting genotypes in leaves, white fruit, and red fruit. Variations in sucrose concentrations/efflux indicated genetic variation underlying sucrose accumulation and transportation during fruit ripening. Integration of genome-wide association studies and expression quantitative locus mapping identified starch synthase 4 (FxaC_10g00830) and sugar transporter 2-like candidate genes (FxaC_21g51570) within the respective QTL intervals. These results will enable immediate applications in genomics-assisted breeding for flavor and further study of candidate genes underlying genetic variation of sugar accumulation in strawberry fruit.

The predictive value of neurally adjusted ventilatory assist indexes for the prognosis of patients with severe cerebral hemorrhage.

OBJECTIVE: This study assessed the predictive value of electrical activity of the diaphragm (EAdi) and the EAdi-derived monitoring index in the prognosis of patients with severe cerebral hemorrhage. METHODS: Ninety patients with severe cerebral hemorrhage were admitted to the Neurosurgery Intensive Care Unit of Yijishan Hospital from April 2019 to June 2021 and were divided into the good prognosis group (Glasgow Outcome Scale [GOS] ≥ 4) and poor prognosis group (GOS ≤ 3). The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate prediction accuracy. RESULTS: EAdi, neuro-ventilatory efficiency (NVE), and neuro-muscular efficiency (NME) in patients with good prognosis were significantly higher than those in patients with poor prognosis (4.707 µV vs 2.80 µV, P < 0.001; 141.85 ml/µV vs 66.01 ml/µV, P = 0.000; 2.57 cm H2O/µV vs 1.37 cm H2O/µV, P = 0.000). The area under the ROC curve for the EAdi score was 0.719, with sensitivity of 69.70% and specificity of 68.42% when EAdi was 3.6 µV. The AUC for NVE score was 0.793, with sensitivity of 75.76% and specificity of 75.44% when the NVE value was 95.32 ml/µV. The AUC for NME score was 0.792, with sensitivity of 69.70% and specificity of 78.95% when the NME value was 2.06 H2O/µV. The 6-month survival time of patients with higher EAdi, NVE, and NME was significantly longer than that of patients with lower EAdi, NVE, and NME CONCLUSION: EAdi, NVE, and NME can be used as indices for predicting the prognosis of patients with severe cerebral hemorrhage. TRIAL REGISTRATION NO: ChiCTR1900022861. Registered April 28, 2019, http://www.chictr.org.cn .

A Machine Learning Force Field for Bio-Macromolecular Modeling Based on Quantum Chemistry-Calculated Interaction Energy Datasets.

Accurate energy data from noncovalent interactions are essential for constructing force fields for molecular dynamics simulations of bio-macromolecular systems. There are two important practical issues in the construction of a reliable force field with the hope of balancing the desired chemical accuracy and working efficiency. One is to determine a suitable quantum chemistry level of theory for calculating interaction energies. The other is to use a suitable continuous energy function to model the quantum chemical energy data. For the first issue, we have recently calculated the intermolecular interaction energies using the SAPT0 level of theory, and we have systematically organized these energies into the ab initio SOFG-31 (homodimer) and SOFG-31-heterodimer datasets. In this work, we re-calculate these interaction energies by using the more advanced SAPT2 level of theory with a wider series of basis sets. Our purpose is to determine the SAPT level of theory proper for interaction energies with respect to the CCSD(T)/CBS benchmark chemical accuracy. Next, to utilize these energy datasets, we employ one of the well-developed machine learning techniques, called the CLIFF scheme, to construct a general-purpose force field for biomolecular dynamics simulations. Here we use the SOFG-31 dataset and the SOFG-31-heterodimer dataset as the training and test sets, respectively. Our results demonstrate that using the CLIFF scheme can reproduce a diverse range of dimeric interaction energy patterns with only a small training set. The overall errors for each SAPT energy component, as well as the SAPT total energy, are all well below the desired chemical accuracy of ~1 kcal/mol.

Type of anesthesia for endovascular therapy in acute ischemic stroke: A literature review and meta-analysis.

BACKGROUND: Endovascular thrombectomy (EVT) has been proven as the standard treatment for acute ischemic stroke (AIS) patients due to large vessel occlusion (LVO). However, the ideal anesthetic strategy during EVT still remains unclear. Therefore, this systematic review and meta-analysis aimed to determine the optimal anesthetic modality for patients with AIS undergoing EVT based on current randomized controlled trials (RCTs). METHODS: The databases Medline (via PubMed), EMBASE, Web of Science, and the Cochrane Library were searched for RCTs comparing general anesthesia (GA) and conscious sedation (CS) in AIS patients undergoing EVT. The primary outcome was a favorable functional outcome at 90 days postintervention. Data analysis was conducted using the Review Manager software (RevMan V.5.3). RESULTS: Eight RCTs involving 1199 patients were included. There was no significant difference between GA and CS group in the rate of functional independence (risk ratio (RR) = 1.10, 95% confidence interval (CI) = 0.96 to 1.25; p = 0.17; I2 = 30%). Compared with the CS group, the GA group attained a higher successful recanalization rate (RR = 1.14, 95% CI = 1.08 to 1.20; p < 0.00001; I2 = 17%). In addition, patients in the GA were associated with a higher rate of hypotension (RR = 1.87, 95% CI = 1.44 to 2.41; p < 0.00001; I2 = 66%) and a higher incidence of pneumonia (RR = 1.38, 95% CI = 1.05 to 1.8; p = 0.02; I2 = 37%). CONCLUSION: For AIS patients receiving EVT, the choice of anesthetic modality did not influence the 3-month neurological outcome while GA is superior to CS in terms of successful reperfusion rate. Moreover, the patients in the GA group were at a higher risk of developing hypotension and pneumonia. Further studies are required to provide more sufficient evidence.

SIRT3/6: an amazing challenge and opportunity in the fight against fibrosis and aging.

Fibrosis is a typical aging-related pathological process involving almost all organs, including the heart, kidney, liver, lung, and skin. Fibrogenesis is a highly orchestrated process defined by sequences of cellular response and molecular signals mechanisms underlying the disease. In pathophysiologic conditions associated with organ fibrosis, a variety of injurious stimuli such as metabolic disorders, epigenetic changes, and aging may induce the progression of fibrosis. Sirtuins protein is a kind of deacetylase which can regulate cell metabolism and participate in a variety of cell physiological functions. In this review, we outline our current understanding of common principles of fibrogenic mechanisms and the functional role of SIRT3/6 in aging-related fibrosis. In addition, sequences of novel protective strategies have been identified directly or indirectly according to these mechanisms. Here, we highlight the role and biological function of SIRT3/6 focus on aging fibrosis, as well as their inhibitors and activators as novel preventative or therapeutic interventions for aging-related tissue fibrosis.

Shared and malignancy-specific functional plasticity of dynamic brain properties for patients with left frontal glioma.

The time-varying brain activity may parallel the disease progression of cerebral glioma. Assessment of brain dynamics would better characterize the pathological profile of glioma and the relevant functional remodeling. This study aims to investigate the dynamic properties of functional networks based on sliding-window approach for patients with left frontal glioma. The generalized functional plasticity due to glioma was characterized by reduced dynamic amplitude of low-frequency fluctuation of somatosensory networks, reduced dynamic functional connectivity between homotopic regions mainly involving dorsal attention network and subcortical nuclei, and enhanced subcortical dynamic functional connectivity. Malignancy-specific functional remodeling featured a chaotic modification of dynamic amplitude of low-frequency fluctuation and dynamic functional connectivity for low-grade gliomas, and attenuated dynamic functional connectivity of the intrahemispheric cortico-subcortical connections and reduced dynamic amplitude of low-frequency fluctuation of the bilateral caudate for high-grade gliomas. Network dynamic activity was clustered into four distinct configuration states. The occurrence and dwell time of the weakly connected state were reduced in patients' brains. Support vector machine model combined with predictive dynamic features achieved an averaged accuracy of 87.9% in distinguishing low- and high-grade gliomas. In conclusion, dynamic network properties are highly predictive of the malignant grade of gliomas, thus could serve as new biomarkers for disease characterization.

Genomic signatures of strawberry domestication and diversification.

Cultivated strawberry (Fragaria × ananassa) has a brief history of less than 300 yr, beginning with the hybridization of octoploids Fragaria chiloensis and Fragaria virginiana. Here we explored the genomic signatures of early domestication and subsequent diversification for different climates using whole-genome sequences of 289 wild, heirloom, and modern varieties from two major breeding programs in the United States. Four nonadmixed wild octoploid populations were identified, with recurrent introgression among the sympatric populations. The proportion of F. virginiana ancestry increased by 20% in modern varieties over initial hybrids, and the proportion of F. chiloensis subsp. pacifica rose from 0% to 3.4%. Effective population size rapidly declined during early breeding. Meanwhile, divergent selection for distinct environments reshaped wild allelic origins in 21 out of 28 chromosomes. Overlapping divergent selective sweeps in natural and domesticated populations revealed 16 convergent genomic signatures that may be important for climatic adaptation. Despite 20 breeding cycles since initial hybridization, more than half of loci underlying yield and fruit size are still not under artificial selection. These insights add clarity to the domestication and breeding history of what is now the most widely cultivated fruit in the world.

Development and evaluation of neutralizing antibodies for cross-protection against West Nile virus and Japanese encephalitis virus.

Background: West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses, and is fatal for birds, chickens and other poultry. With no specific drugs or vaccines available, antibody-based therapy is a promising treatment. This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus. Methods: Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology. The therapeutic efficacy of these antibodies was evaluated using a mouse model, and a humanized version of the monoclonal antibody was generated for potential human application. Results: In this study, we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV. Their therapeutic effects against WNV were validated both in vivo and in vitro. Among these antibodies, C9-G11-F3 also exhibited cross-protective activity against JEV. We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans. Conclusion: This study highlights the importance of neutralizing antibodies as a promising approach for protection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.

Hepatic venous pressure gradient: Inaccurately estimates portal venous pressure gradient in alcoholic cirrhosis and portal hypertension.

BACKGROUND: Portal hypertension (PHT) in patients with alcoholic cirrhosis causes a range of clinical symptoms, including gastroesophageal varices and ascites. The hepatic venous pressure gradient (HVPG), which is easier to measure, has replaced the portal venous pressure gradient (PPG) as the gold standard for diagnosing PHT in clinical practice. Therefore, attention should be paid to the correlation between HVPG and PPG. AIM: To explore the correlation between HVPG and PPG in patients with alcoholic cirrhosis and PHT. METHODS: Between January 2017 and June 2020, 134 patients with alcoholic cirrhosis and PHT who met the inclusion criteria underwent various pressure measurements during transjugular intrahepatic portosystemic shunt procedures. Correlations were assessed using Pearson's correlation coefficient to estimate the correlation coefficient (r) and determination coefficient (R2). Bland-Altman plots were constructed to further analyze the agreement between the measurements. Disagreements were analyzed using paired t tests, and P values < 0.05 were considered statistically significant. RESULTS: In this study, the correlation coefficient (r) and determination coefficient (R2) between HVPG and PPG were 0.201 and 0.040, respectively (P = 0.020). In the 108 patients with no collateral branch, the average wedged hepatic venous pressure was lower than the average portal venous pressure (30.65 ± 8.17 vs. 33.25 ± 6.60 mmHg, P = 0.002). Hepatic collaterals were identified in 26 cases with balloon occlusion hepatic venography (19.4%), while the average PPG was significantly higher than the average HVPG (25.94 ± 7.42 mmHg vs 9.86 ± 7.44 mmHg; P < 0.001). The differences between HVPG and PPG < 5 mmHg in the collateral vs no collateral branch groups were three cases (11.54%) and 44 cases (40.74%), respectively. CONCLUSION: In most patients, HVPG cannot accurately represent PPG. The formation of hepatic collaterals is a vital reason for the strong underestimation of HVPG.