Effect of duloxetine on pain relief after total knee arthroplasty: A meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative pain is one of the most feared complications of total knee arthroplasty. Recently, randomized controlled trials have compared the efficacy of duloxetine in patients undergoing total knee arthroplasty. However, there is no definite answer as to the efficacy and safety of duloxetine. METHODS: Randomized controlled trials about relevant studies were searched from PubMed (1996 to July 2022), Embase (1996 to July 2022), and Cochrane Library (CENTRAL, July 2022). RESULTS: Six high-quality studies containing 532 patients met the inclusion criteria. Results show patients in the duloxetine group had better performance in terms of visual analog scale (P < .05), equivalent morphine consumption (P < .05), and length of stay (P < .05). CONCLUSION: Duloxetine can be used to reduce pain after knee arthroplasty in selected patients.

miR-181b promotes angiogenesis and neurological function recovery after ischemic stroke.

Promotion of new blood vessel formation is a new strategy for treating ischemic stroke. Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke. miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model, while its effect on ischemic stroke remains elusive. In this study, we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell proliferation and enhanced angiogenesis. In rat models of focal cerebral ischemia, overexpression of miR-181b reduced infarction volume, promoted angiogenesis in ischemic penumbra, and improved neurological function. We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3'-UTR of phosphatase and tensin homolog (PTEN) mRNA to induce PTEN downregulation, leading to activation of the protein kinase B (Akt) pathway, upregulated expression of vascular endothelial growth factors, down-regulated expression of endostatin, and promoted angiogenesis. Taken together, these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stroke through activating the PTEN/Akt signal pathway and promoting angiogenesis.

Palaeobotanical evidence reveals the living conditions of Miocene Lufengpithecus in East Asia.

BACKGROUND: Understanding the relationship between human evolution and environmental changes is the key to lifting the veil on human origin. The hypothesis that environmental changes triggered the divergence of humans from apes (ca. 9.3-6.5 million years ago, Ma) has been poorly tested because of limited continuous environmental data from fossil localities. Lufengpithecus (12.5-6.0 Ma) found on the southeastern margin of the Tibetan Plateau (SEMTP) across the ape-human split provides a good chance for testing this hypothesis. RESULTS: Here, we reconstructed the habitats of L. keiyuanensis (12.5-11.6 Ma) with comprehensive vegetation, climate, and potential food web data by palaeobotanical evidence, together with other multidisciplinary data and partly tested the environment-driven hypothesis by revealing the living conditions of Lufengpithecus. CONCLUSION: A detailed comparison of hominoids on different continents reveals their behaviour and fate divergence across the ape-human split against the background of global climate change, i.e., the stable living conditions of SEMTP not only provided a so-called 'refuge' for arboreal Lufengpithecus but also acted as a 'double-edged sword', preventing their further evolution while vegetation shifts in East Africa probably stimulated the emergence of human bipedalism, and the intense climatic changes in Europe possibly prevented those hominoids from surviving that time interval. Our findings provide interesting insight into the environmental impacts on the behavioural evolution of hominoids.

Subject Separation Network for Reducing Calibration Time of MI-Based BCI.

Motor imagery brain-computer interface (MI-based BCIs) have demonstrated great potential in various applications. However, to well generalize classifiers to new subjects, a time-consuming calibration process is necessary due to high inter-subject variabilities of EEG signals. This process is costly and tedious, hindering the further expansion of MI-based BCIs outside of the laboratory. To reduce the calibration time of MI-based BCIs, we propose a novel domain adaptation framework that adapts multiple source subjects' labeled data to the unseen trials of target subjects. Firstly, we train one Subject Separation Network(SSN) for each of the source subjects in the dataset. Based on adversarial domain adaptation, a shared encoder is constructed to learn similar representations for both domains. Secondly, to model the factors that cause subject variabilities and eliminate the correlated noise existing in common feature space, private feature spaces orthogonal to the shared counterpart are learned for each subject. We use a shared decoder to validate that the model is actually learning from task-relevant neurophysiological information. At last, an ensemble classifier is built by the integration of the SSNs using the information extracted from each subject's task-relevant characteristics. To quantify the efficacy of the framework, we analyze the accuracy-calibration cost trade-off in MI-based BCIs, and theoretically guarantee a generalization bound on the target error. Visualizations of the transformed features illustrate the effectiveness of domain adaptation. The experimental results on the BCI Competition IV-IIa dataset prove the effectiveness of the proposed framework compared with multiple classification methods. We infer from our results that users could learn to control MI-based BCIs without a heavy calibration process. Our study further shows how to design and train Neural Networks to decode task-related information from different subjects and highlights the potential of deep learning methods for inter-subject EEG decoding.

Contribution of UDP-glycosyltransferases to chlorpyrifos resistance in Nilaparvata lugens.

As a multigene superfamily of Phase II detoxification enzymes, uridine diphosphate (UDP)-glycosyltransferases (UGTs) play important roles in the metabolism of xenobiotics including insecticides. In this study, 5-nitrouracil, an inhibitor of UGT enzyme activity, effectively increased the toxicity of chlorpyrifos to the chlorpyrifos-resistant strain of Nilaparvata lugens, one of the most resistant rice pests. The enzyme content of UGT in the resistant strain was significantly higher than that in the susceptible strain. Among 20 identified UGT genes, UGT386H2, UGT386J2, UGT386N2 and UGT386P1 were found significantly overexpressed in the resistant strain and can be effectively induced by chlorpyrifos. These four UGT genes were most highly expressed in the midgut and/or fat body, two main insect detoxification tissues. Amino acid sequence alignments revealed that these four UGTs contained a variable N-terminal substrate-binding domain and a conserved C-terminal sugar donor-binding domain. Furthermore, homology modeling and molecular docking analyses showed that these UGTs could stably bind to chlorpyrifos and chlorpyrifos oxon, with the binding free energies from -19.4 to -110.62 kcal mol-1. Knockdown of UGT386H2 or UGT386P1 by RNA interference dramatically increased the susceptibility of the resistant strain to chlorpyrifos. These findings suggest that overexpression of these two UGT genes contributes to chlorpyrifos resistance in N. lugens.

Synthesis of a BINOL-Based C3 Symmetric Schiff Base and Its Fluorescence Response to Zn2.

A novel C3 symmetric 1,1'-bi-2-naphthol-based Schiff base (R,R,R)-6 has been synthesized which shows highly selective fluorescence enhancement with Zn2+ among 21 metal cations examined. Its sensitivity and selectivity are found to be greater than other related C2 (1) and C1 [(R)-9] symmetric compounds in the fluorescent recognition of Zn2+ . The mechanistic study reveals that the selective fluorescence enhancement of the probe can be attributed to the formation of a unimolecular multidentate 6-coordinated Zn2+ complex.

Protein Acetylation Increased Risk of Fibrosis-Related Liver Cancer.

Objective: The occurrence of liver fibrosis and fibrosis-related liver cancer is the reason for the increase in morbidity and mortality worldwide. Transforming growth factor-ß2 (TGF-ß2) is an important mediator of chronic liver fibrosis. This study aims to find the molecular mechanism that mediates HBV infection and induces TGF-ß2 and verifies that CREB binding protein acetylation mediates HBV infection and induces TGF-ß2 expression. Methods: The acetylated proteins were extracted from HepG2-NTCP cells and HBV-infectedHepG2-NTCP cells. The acetylated proteins were screened by modification enrichment technology and database search. Protein annotation, motif analysis of modification sites, and protein function enrichment analysis of these proteins were performed to roughly clarify the location and function of these acetylated modification proteins in cells. Acylated proteins enriched in the TGF-ß pathway were obtained by KEGG pathway enrichment analysis. The effect of the selected acetylated modification protein on the TGF-ß pathway was verified by experiments, that is, the target protein gene was knocked out by siRNA, and the expression level of the TGF-ß2 was detected by qRT-PCR. Results: Proteins were extracted from HepG2-NTCP cells and HepG2-NTCP cells infected with HBV, and differential acetylation modification proteins were screened. The target protein CREB binding protein was screened by modification enrichment technology and database search. The aggregation analysis of TGF-ß pathway showed that CREB binding protein was acetylated at amino acid positions 434 and 439, and enriched in the TGF-ß signaling pathway. siRNA targeting CREB binding protein was transfected, and the expression of TGF-ß2 in cells was detected by qRT-PCR and western blot, respectively. It was verified that HBV infection-inducedCREB-binding protein acetylation regulated the high expression of TGF-ß2. Conclusion: After HBV infection, CREBBP acetylation was up-regulated, which promoted the high expression of TGF-ß2.

Anti-inflammatory and analgesic effect of Forsythiaside B on complete Freund's adjuvant-induced inflammatory pain in mice.

Chronic pain is frequently reported in clinical practice. Therefore, it is important to identify effective therapy to relieve pain. In this work, we selected Forsythoside B (FB), a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, to evaluate its effect in modulating inflammatory pain induced by complete Freund's adjuvant (CFA) and the involved mechanisms. We discovered that FB could attenuate inflammatory pain triggered by CFA injection and exert anti-anxiety effects. In detail, proinflammatory cytokines, consisting of IL-6 and TNF-α, were decreased after FB administration in the CFA-injected mice. Furthermore, the FB application ameliorated the activation of ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), the microglia and astrocytes markers respectively. Therefore, our findings indicate that FB could be a promising treatment for chronic inflammatory pain.

Plasma transfusion-transmission of Zika virus in mice and macaques.

BACKGROUND: Zika virus (ZIKV) epidemics with infections in pregnant women are associated with severe neurological disease in newborns. Although an arbovirus, ZIKV is also blood transfusion-transmitted (TT). Greater knowledge of the efficiency of ZIKV TT would aid decisions on testing and pathogen reduction technologies (PRT). STUDY DESIGN AND METHODS: Plasma units from ZIKV RNA-reactive blood donors were used to study infectivity in vitro, in mice, and in macaques. Furthermore, plasma units were subjected to PRT using amotosalen/ultraviolet light A (A/UVA) before transfusion. RESULTS: In vitro infectivity of ZIKV RNA-reactive plasma varied between 100 and 1000 international units (IU) of ZIKV RNA. Immunodeficient mice were more sensitive with as low as 32 IU sufficient to infect 50% of mice. 50-5500 IU of RNA led to TT in macaques using dose escalation of three different RNA-positive, seronegative plasma units. In contrast, RNA-reactive units collected postseroconversion were not infectious in macaques, even at a dose of 9 million IU RNA. After A/UVA PRT, transfusion of plasma containing up to 18 million IU was no longer infectious in vitro and did not result in ZIKV TT in macaques. CONCLUSION: Significant risks of ZIKV TT are likely confined to a relatively short viremic window before seroconversion, and that sensitive nucleic acid amplification testing likely identifies the majority of infectious plasma. PRT was demonstrated to be effective at preventing ZIKV TT. Considering that there is no approved ZIKV vaccine, these data are relevant to mitigate the risk of TT during the future ZIKV outbreaks.

A 6-month prognostic nomogram incorporating hemoglobin level for intracerebral hemorrhage in younger adults.

OBJECTIVE: Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, with high mortality and morbidity. At present, there are no effective 6-month prognostic markers, particularly for younger patients. The aim of this research was to construct a new valuable prognostic nomogram model incorporating haemoglobin levels for adult patients with ICH. METHODS: Patients aged between 18 and 50 presenting with intracerebral haemorrhage at the Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 1st 2012 and December 31st 2018 were included in this retrospective study. Independent factors of prognosis were identified by univariate and multivariate logistic regression analyses, and a new nomogram model was constructed and validated. The clinical value of the nomogram model was subsequently explored utilizing decision curve analysis and clinical impact curves. RESULTS: In total, 565 patients were enrolled in this study, 117 (20.7%) of whom developed an unfavourable prognosis. Infratentorial lesion (adjusted odds ratio [aOR] = 3.708, 95% confidence interval [CI], 1.490-9.227; P = 0.005) was the most significant unfavourable outcome. Age ([aOR] = 1.054; 95% CI, 1.014-1.096; P = 0.008), hematoma volume (aOR = 1.014, 95% CI, 1.002-1.027; P = 0.024), haemoglobin (aOR = 0.981, 95% CI, 0.969-0.993; P = 0.002), blood glucose (aOR = 1.135, 95% CI, 1.037-1.241; P = 0.005) and NIHSS (aOR = 1.105, 95% CI, 1.069-1.141; P < 0.001) were independent risk factors. Based on these 6 factors, the nomogram can be employed to predict early functional prognosis with high accuracy (AUC 0.791). Decision curve analysis and clinical impact curves showed an increased net benefit for utilizing the nomogram. CONCLUSION: The haemoglobin level at admission may be an easily overlooked factor in clinical work. This new nomogram model could be a promising and convenient tool to predict the early functional prognosis of adults with ICH. More prospective multicentre studies are needed to validate these findings.

Cytotoxic T-lymphocyte antigen 4 polymorphisms and breast cancer susceptibility: Evidence from a meta-analysis.

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an immune checkpoint and regulates the immune function of T cells. However, previous findings regarding the association of CTLA-4 polymorphisms and breast cancer remain inconclusive. Therefore, we performed a meta-analysis to investigate the potential effects of five polymorphisms (-1722 T/C, -1661 A/G -318 C/T, +49 A/G, and CT60 A/G) in the CTLA-4 gene on breast cancer susceptibility. METHODS: Relevant literatures were systematically searched through electronic databases including PubMed, EMBASE, and Web of Science up to October 10, 2021. Available data were extracted and odds ratios (ORs) with 95% confidence intervals were used to estimate the pooling effect size. The Newcastle-Ottawa Scale was applied for assessing the quality of included studies. We conducted subgroup analyses based on ethnicity and control sources to explore levels of heterogeneity. Moreover, sensitivity analysis and publication bias were assessed. RESULTS: Finally, a total of 12 eligible studies regarding CTLA-4 polymorphisms and breast cancer were included. For overall analyses, only the +49 A/G polymorphism was significantly associated with breast cancer under allelic (OR = 1.19), dominant (OR = 1.27), and recessive (OR = 1.27) models. Ethnicity-based subgroup analysis found that the +49 A/G polymorphism has a significant risk (OR = 2.03) of breast cancer under the recessive model in the non-Asian population. Studies with hospital-based controls showed that the +49 A/G polymorphism has significant breast cancer risks under allelic (OR = 1.44), dominant (OR = 1.86), and recessive (OR = 1.60) models. In addition, those with population-based controls found that -1722 T/C polymorphism has a significant breast cancer risk under allelic (OR = 1.19) and dominant (OR = 1.26) models. CONCLUSION: This meta-analysis suggested that CTLA-4 + 49 A/G polymorphism may significantly associate with breast cancer susceptibility. Future studies containing various populations are helpful for evaluating the impacts of CTLA-4 polymorphisms on breast cancer susceptibility.

The PPR-Domain Protein SOAR1 Regulates Salt Tolerance in Rice.

Previous studies in Arabidopsis reported that the PPR protein SOAR1 plays critical roles in plant response to salt stress. In this study, we reported that expression of the Arabidopsis SOAR1 (AtSOAR1) in rice significantly enhanced salt tolerance at seedling growth stage and promoted grain productivity under salt stress without affecting plant productivity under non-stressful conditions. The transgenic rice lines expressing AtSOAR1 exhibited increased ABA sensitivity in ABA-induced inhibition of seedling growth, and showed altered transcription and splicing of numerous genes associated with salt stress, which may explain salt tolerance of the transgenic plants. Further, we overexpressed the homologous gene of SOAR1 in rice, OsSOAR1, and showed that transgenic plants overexpressing OsSOAR1 enhanced salt tolerance at seedling growth stage. Five salt- and other abiotic stress-induced SOAR1-like PPRs were also identified. These data showed that the SOAR1-like PPR proteins are positively involved in plant response to salt stress and may be used for crop improvement in rice under salinity conditions through transgenic manipulation.

Gold Nanoparticles Enhancing Generation of ROS for Cs-137 Radiotherapy.

Radiotherapy is an important modality for the treatment of cancer, e.g., X-ray, Cs-137 γ-ray (peak energy: 662 keV). An important therapy pathway of radiation is to generate the double strand breaks of DNA to prohibit the proliferation of cancer cells. In addition, the excessive amount of reactive oxygen species (ROS) is induced to damage the organelles, which can cause cellular apoptosis or necrosis. Gold nanoparticles (GNPs) have been proven potential as a radiosensitizer due to the high biocompatibility, the low cytotoxicity and the high-Z property (Z = 79) of gold. The latter property may allow GNPs to induce more secondary electrons for generating ROS in cells as irradiated by high-energy photons. In this paper, the radiobiological effects on A431 cells with uptake of 55-nm GNPs were studied to investigate the GNPs-enhanced production of ROS on these cells as irradiated by Cs-137 γ-ray. The fluorescence-labeling image of laser scanning confocal microscopy (LSCM) shows the excessive expression of ROS in these GNPs-uptake cells after irradiation. And then, the follow-up disruption of cytoskeletons and dysfunction of mitochondria caused by the induced ROS are observed. From the curves of cell survival fraction versus the radiation dose, the radiosensitization enhancement factor of GNPs is 1.29 at a survival fraction of 30%. This demonstrates that the tumoricidal efficacy of Cs-137 radiation can be significantly raised by GNPs. Because of facilitating the production of excessive ROS to damage tumor cells, GNPs are proven to be a prospective radiosensitizer for radiotherapy, particularly for the treatment of certain radioresistant tumor cells. Through this pathway, the tumoricidal efficacy of radiotherapy can be raised.

Chlorinated Organophosphate Flame Retardants Impair the Lung Function via the IL-6/JAK/STAT Signaling Pathway.

Toxicological studies have revealed the adverse impacts of organophosphate flame retardants (OPFRs) on the respiratory system, while there is a lack of epidemiological evidence, and information for risk assessment remains insufficient. Herein, we investigated the associations of urinary metabolites of OPFRs with the lung function in 987 adults participating in the U.S. National Health and Nutrition Examination Survey 2011-2012. The elevation of three primary metabolites of chlorinated OPFRs [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-chloroethyl) phosphate (BCEP), and bis(1-chloro-2-propyl) phosphate (BCIPP)] was related to pulmonary dysfunction in a sample-weighted regression model. Each one-unit increase in the log-transformed levels of BDCIPP and BCEP was related to 91.52 and 79.34 mL reductions in the forced vital capacity (FVC). Each one-unit elevation in BCIPP was correlated with 130.86, 153.56, 302.26, and 148.24 mL reductions in forced expiratory volume 1st second (FEV1), FVC, peak expiratory flow rate (PEF), and forced expiratory flow at 25-75% of FVC (FEF25-75%), respectively. Then, an adverse outcome pathway (AOP) framework was constructed using the Comparative Toxicogenomics Database, the Toxicity Forecaster, and the GeneCards database. Based on the weight of the evidence, BDCIPP, BCEP, BCIPP, and their parent compounds (TDCIPP, TCEP, and TCIPP) may affect the IL-6/Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, induce airway remodeling, and impair the lung function. Additionally, tobacco smoke exposure may modify the effects of BDCIPP on the lung function (Pint < 0.05) and affect the IL-6-mediated AOP. These results suggested that chlorinated OPFRs were associated with pulmonary dysfunction via the IL-6/JAK/STAT pathway.

Cognitive function and delirium following sevoflurane or propofol anesthesia for valve replacement surgery: A multicenter randomized controlled trial.

Cognitive dysfunction is a common postoperative neurological complication in patients undergoing valve replacement surgery. This study aimed to compare the effects of sevoflurane versus propofol-based total intravenous anesthesia on the incidence of cognitive dysfunction following valve replacement surgery. This multicenter, randomized, controlled double-blinded study was conducted in three teaching hospitals in China. Patients receiving on-pump valve replacement surgery were enrolled. Stratified block randomization was used to randomly assign patients 1:1 to receive sevoflurane (1.0-1.5 MAC) or propofol (2.0-3.0 mg/kg/h) for anesthesia maintenance. The primary outcome was the incidence of cognitive dysfunction assessed by four cognitive tests before, as well as 7-14 days after surgery. Patients were randomly assigned to receive sevoflurane anesthesia (n = 144) or propofol-based total intravenous anesthesia (n = 145). The incidence of postoperative cognitive dysfunction in the sevoflurane anesthesia group (31.9%) was significantly lower than that in the total intravenous anesthesia group (43.4%; relative risk 0.61, 95% confidence interval [CI]: 0.38-0.97, p = 0.044). There was no difference in the incidence of delirium between patients receiving sevoflurane and total intravenous anesthesia (27.8% [35/144] vs. 25.9% [35/145], 1.10, 95% CI: 0.64 to 1.90, p = 0.736). There was a significant difference in the Katz Index on day 3 after surgery (3 [0.9) vs. 3 (1.0], 0.095, 95% CI: 0.05 to 0.43, p = 0.012). No difference was observed in other outcomes between the two groups. For patients undergoing on-pump valve replacement surgery, sevoflurane anesthesia had a smaller effect on cognitive function and independence in daily life activities compared with propofol anesthesia.

Computational Study of Fenestration and Parallel Grafts Used in TEVAR of Aortic Arch Aneurysms.

To explore the differences between fenestration technique and parallel grafts technique of thoracic endovascular aortic repair, and evaluate the risk of complications after interventional treatment of aortic arch aneurysms. A three-dimensional aortic model was established from the follow-up imaging data of patient who reconstructed the superior arch vessel by the chimney technique, which was called the chimney model. Based on the chimney model, the geometric of the reconstructed vessel was modified by virtual surgery, and the normal model, fenestration model and periscope model were established. The blood flow waveforms measured by 2D phase contrast magnetic resonance imaging were processed as the boundary conditions of the ascending aorta inlet and the superior arch vessels outlets of the normal model. The pressure waveform of descending aorta was obtained using three-element Windkessel model, and specific pressure boundary conditions were imposed at reconstructed branches for the postoperative models. Through computational fluid dynamics simulations, the hemodynamic parameters of each model were obtained. The reconstructed vessel flow rate of the periscope model and the fenestration model are 33% and 50% of that of the normal model, respectively. The pressure difference between the inner and outer walls of the fenestration stent and periscope stent is 3.15 times and 7.56 times that of the chimney stent. The velocity in the fenestration stent and periscope stent is uneven. The high relative residence time is concentrated in the region around the branch stents, which is prone to thrombosis. The "gutter" part of the chimney model may become larger due to the effect of the stent-graft DF, increasing the risk of endoleak. For patients with incomplete circle of Willis, the periscope technique to reconstruct the supra-arch vessels may affect blood perfusion. It is recommended to use balloon-expandable stent for fenestration stent and periscope stent, and self-expanding stent for chimney stent. For patients with aortic arch aneurysms, the fenestration technique may be superior to the parallel grafts technique. This article is protected by copyright. All rights reserved.

A high-throughput screening assay to identify inhibitory antibodies targeting alphavirus release.

BACKGROUND: Several studies have demonstrated neutralizing antibodies to be highly effective against alphavirus infection in animal models, both prophylactically and remedially. In most studies, neutralizing antibodies have been evaluated for their ability to block viral entry in vitro but recent evidence suggests that antibody inhibition through other mechanisms, including viral budding/release, significantly contributes to viral control in vivo for a number of alphaviruses. RESULTS: We describe a BSL-2, cell-based, high-throughput screening system that specifically screens for inhibitors of alphavirus egress using chikungunya virus (CHIKV) and Mayaro virus (MAYV) novel replication competent nano-luciferase (nLuc) reporter viruses. Screening of both polyclonal sera and memory B-cell clones from CHIKV immune individuals using the optimized assay detected several antibodies that display potent anti-budding activity. CONCLUSIONS: We describe an "anti-budding assay" to specifically screen for inhibitors of viral egress using novel CHIKV and MAYV nLuc reporter viruses. This BSL-2 safe, high-throughput system can be utilized to explore neutralizing "anti-budding" antibodies to yield potent candidates for CHIKV and MAYV therapeutics and prophylaxis.

Advantages of Transmuscular Quadratus Lumborum Block via Subfascial Approach Versus Extrafascial Approach for Postoperative Analgesia After Laparoscopic Cholecystectomy: A Randomized Controlled Study.

OBJECTIVE: We aimed to compare the analgesic effect and incidence of lower limb weakness of transmuscular quadratus lumborum (TQL) block via subfascial approach with that via extrafascial after laparoscopic cholecystectomy (LC). METHODS: Eighty patients undergoing LC were randomized to receive ultrasound-guided bilateral TQL block via subfascial (subfascial group) or extrafascial (extrafascial group) using 30 mL of 0.33% ropivacaine unilaterally. Pain scores of port sites while rest and coughing at 1, 6, 12, 24, 36, and 48 hours postoperatively as primary outcome were compared. Modified Lovett Rating Scale, ambulatory dependency, and rescue analgesia requirement was also compared. RESULTS: The pain score of the subxiphoid and of the right subcostal port site for up to the postoperative 36 hours (2 [1 to 2]) and 24 hours (2 [2 to 3]) in the subfascial group was significantly lower than that in extrafascial group (2 [2 to 2] and 3 [2.25 to 4]). Up to postoperative 24 hours, the rescue analgesia requirement in subfascial group was significantly lower than that in extrafascial group, namely less fentanyl consumption and parecoxib (1.3 [±5.5] µg vs. 5.6 [±10.6] µg; 17.5% vs. 37.5%). The ratio of patients with LRS score of 6 at postoperative 1 hour (65.0%), and with dependent ambulation at postoperative 1 and 6 hours in subfascial group (15.0% and 0.0%) was significantly lower than that in extrafascial group (10.0%, 80.0%, and 17.5%). CONCLUSION: TQL block via subfascial had the advantages of better analgesic effect and less lower limbs weakness after LC over that via extrafascial.

Phosphorylation of a wheat aquaporin at two sites enhances both plant growth and defense.

Eukaryotic aquaporins share the characteristic of functional multiplicity in transporting distinct substrates and regulating various processes, but the underlying molecular basis for this is largely unknown. Here, we report that the wheat (Triticum aestivum) aquaporin TaPIP2;10 undergoes phosphorylation to promote photosynthesis and productivity and to confer innate immunity against pathogens and a generalist aphid pest. In response to elevated atmospheric CO₂ concentrations, TaPIP2;10 is phosphorylated at the serine residue S280 and thereafter transports CO₂ into wheat cells, resulting in enhanced photosynthesis and increased grain yield. In response to apoplastic H₂O₂ induced by pathogen or insect attacks, TaPIP2;10 is phosphorylated at S121 and this phosphorylated form transports H₂O₂ into the cytoplasm, where H₂O₂ intensifies host defenses, restricting further attacks. Wheat resistance and grain yield could be simultaneously increased by TaPIP2;10 overexpression or by expressing a TaPIP2;10 phosphomimic with aspartic acid substitutions at S121 and S280, thereby improving both crop productivity and immunity.

Comprehensive Molecular Analyses of an SLC Family-Based Model in Stomach Adenocarcinoma.

Background: Solute carrier (SLC) family members are crucial in transporting amino acids across membranes. Amino acids are indispensable for both cancer and immune cells. However, the clinical significance of amino acid transporting SLC members in stomach adenocarcinoma (STAD) remains unclear. This study aimed to develop an SLC family-based model to predict the prognosis and the response of STAD patients to immunotherapy. Methods: A total of 1239 tumor cases were obtained from online databases. The training set (n = 371) consisted of RNA sequencing profiles obtained from The Cancer Genome Atlas (TCGA), while those from Gene Expression Omnibus (GEO) were used as the test set. Subsequently, the clinical characteristics and immune profiles were investigated, and potential immunotherapy response prediction values of the model were assessed. Results: Based on the TCGA cohort, an SLC family-based model was developed using multivariate Cox analysis. All tumor cases were stratified into high- and low-risk groups considering the SLC model. High-risk patients had a worse overall survival (OS) than low-risk patients, consistent with the results of GEO cohorts. Comprehensive analyses revealed that the high-risk group was correlated with aggressiveness-related pathways, whereas the low-risk group had better T helper cell infiltration and stronger immunotherapy response. Compared to the high-risk group, the low-risk group presented increased PD-L1 and tumor mutation burden. Conclusion: This SLC family-based model has the potential to predict the prognosis and immunotherapy outcomes of STAD patients. The survival of patients in the low-risk group was greatly prolonged, and the patients may benefit more from immunotherapy.