A distinct dimer configuration of a diatom Get3 forming a tetrameric complex with its tail-anchored membrane cargo.

BACKGROUND: Most tail-anchored (TA) membrane proteins are delivered to the endoplasmic reticulum through a conserved posttranslational pathway. Although core mechanisms underlying the targeting and insertion of TA proteins are well established in eukaryotes, their role in mediating TA protein biogenesis in plants remains unclear. We reported the crystal structures of algal arsenite transporter 1 (ArsA1), which possesses an approximately 80-kDa monomeric architecture and carries chloroplast-localized TA proteins. However, the mechanistic basis of ArsA2, a Get3 (guided entry of TA proteins 3) homolog in plants, for TA recognition remains unknown. RESULTS: Here, for the first time, we present the crystal structures of the diatom Pt-Get3a that forms a distinct ellipsoid-shaped tetramer in the open (nucleotide-bound) state through crystal packing. Pulldown assay results revealed that only tetrameric Pt-Get3a can bind to TA proteins. The lack of the conserved zinc-coordination CXXC motif in Pt-Get3a potentially leads to the spontaneous formation of a distinct parallelogram-shaped dimeric conformation in solution, suggesting a new dimer state for subsequent tetramerization upon TA targeting. Pt-Get3a nonspecifically binds to different subsets of TA substrates due to the lower hydrophobicity of its α-helical subdomain, which is implicated in TA recognition. CONCLUSIONS: Our study provides new insights into the mechanisms underlying TA protein shielding by tetrameric Get3 during targeting to the diatom's cell membrane.

Augmenting Neutrophil Extracellular Traps with Carbonized Polymer Dots: A Potential Treatment for Bacterial Sepsis.

Sepsis is a life-threatening condition that can progress to septic shock as the body's extreme response to pathogenesis damages its own vital organs. Staphylococcus aureus (S. aureus) accounts for 50% of nosocomial infections, which are clinically treated with antibiotics. However, methicillin-resistant strains (MRSA) have emerged and can withstand harsh antibiotic treatment. To address this problem, curcumin (CCM) is employed to prepare carbonized polymer dots (CPDs) through mild pyrolysis. Contrary to curcumin, the as-formed CCM-CPDs are highly biocompatible and soluble in aqueous solution. Most importantly, the CCM-CPDs induce the release of neutrophil extracellular traps (NETs) from the neutrophils, which entrap and eliminate microbes. In an MRSA-induced septic mouse model, it is observed that CCM-CPDs efficiently suppress bacterial colonization. Moreover, the intrinsic antioxidative, anti-inflammatory, and anticoagulation activities resulting from the preserved functional groups of the precursor molecule on the CCM-CPDs prevent progression to severe sepsis. As a result, infected mice treated with CCM-CPDs show a significant decrease in mortality even through oral administration. Histological staining indicates negligible organ damage in the MRSA-infected mice treated with CCM-CPDs. It is believed that the in vivo studies presented herein demonstrate that multifunctional therapeutic CPDs hold great potential against life-threatening infectious diseases.

An RRM domain protein SOE suppresses transgene silencing in rice.

Gene expression is regulated at multiple levels, including RNA processing and DNA methylation/demethylation. How these regulations are controlled remains unclear. Here, through analysis of a suppressor for the OsEIN2 over-expressor, we identified an RNA recognition motif protein SUPPRESSOR OF EIN2 (SOE). SOE is localized in nuclear speckles and interacts with several components of the spliceosome. We find SOE associates with hundreds of targets and directly binds to a DNA glycosylase gene DNG701 pre-mRNA for efficient splicing and stabilization, allowing for subsequent DNG701-mediated DNA demethylation of the transgene promoter for proper gene expression. The V81M substitution in the suppressor mutant protein mSOE impaired its protein stability and binding activity to DNG701 pre-mRNA, leading to transgene silencing. SOE mutation enhances grain size and yield. Haplotype analysis in c. 3000 rice accessions reveals that the haplotype 1 (Hap 1) promoter is associated with high 1000-grain weight, and most of the japonica accessions, but not indica ones, have the Hap 1 elite allele. Our study discovers a novel mechanism for the regulation of gene expression and provides an elite allele for the promotion of yield potentials in rice.

Symbiosis between Dendrobium catenatum protocorms and Serendipita indica involves the plant hypoxia response pathway.

Mycorrhizae are ubiquitous symbioses established between fungi and plant roots. Orchids, in particular, require compatible mycorrhizal fungi for seed germination and protocorm development. Unlike arbuscular mycorrhizal fungi, which have wide host ranges, orchid mycorrhizal fungi are often highly specific to their host orchids. However, the molecular mechanism of orchid mycorrhizal symbiosis is largely unknown compared to that of arbuscular mycorrhizal and rhizobial symbiosis. Here, we report that an endophytic Sebacinales fungus, Serendipita indica, promotes seed germination and the development of protocorms into plantlets in several epiphytic Epidendroideae orchid species (6 species in 2 genera), including Dendrobium catenatum, a critically endangered orchid with high medicinal value. Although plant-pathogen interaction and high meristematic activity can induce the hypoxic response in plants, it has been unclear whether interactions with beneficial fungi, especially mycorrhizal ones, also involve the hypoxic response. By studying the symbiotic relationship between D. catenatum and S. indica, we determined that hypoxia-responsive genes, such as those encoding alcohol dehydrogenase (ADH), are highly induced in symbiotic D. catenatum protocorms. In situ hybridization assay indicated that the ADH gene is predominantly expressed in the basal mycorrhizal region of symbiotic protocorms. Additionally, the ADH inhibitors puerarin and 4-methylpyrazole both decreased S. indica colonization in D. catenatum protocorms. Thus, our study reveals that S. indica is widely compatible with orchids and that ADH and its related hypoxia-responsive pathway are involved in establishing successful symbiotic relationships in germinating orchids.

PCBP1 acts as a regulator of CCL2 expression in macrophages to induce recruitment of monocyte-derived macrophages into the inflamed colon.

Intestinal macrophages with functional plasticity play essential roles in gut immune responses by increasing chemokines and cytokines, thereby contributing to the pathogenesis of inflammatory bowel disease (IBD). Poly(rC)-binding protein 1 (PCBP1), which is widely expressed in immune cells, binds to nucleic acids in mRNA processing, stabilization, translation and transcription. However, little is known about the influence of PCBP1 on macrophages and its specific mechanism in inflamed intestines. In this study, conditional depletion of Pcbp1 in macrophages protected mice from progression of dextran sulfate sodium induced colitis and resulted in significant alleviation of colitis. Pcbp1 deficiency markedly decreased C-C motif chemokine ligand 2 (CCL2) production by colonic CX3C motif chemokine receptor 1+ (CX3CR1+) macrophages and reduced accumulation of pro-inflammatory macrophages and production of pro-inflammatory cytokines, such as IL-6 and TNF-α, in the inflamed colon. RNA-immunoprecipitation analysis indicated that PCBP1 might interact with Ccl2 mRNA and regulate its expression in macrophages. PCBP1 expression in inflamed intestines also correlated significantly with IBD severity in patients, suggesting a critical involvement of PCBP1 in intestinal inflammation. We anticipate that our findings will facilitate the development of novel therapeutic approaches for IBD by targeting the specific function of immune cells in the local microenvironment, thereby helping to reduce adverse effects.

Density Functional Theory Calculations on Fluorescence-Enhanced Mechanisms of the Optical Sensor for Zinc Ions, ADPA.

N-(9-anthracenylmethyl)-N-(2-pyridinylmethyl)-2-pyridinemethanamine (ADPA) as a specific ion sensor for Zn2+ has been widely applied. Although the photo-induced electron transfer (PET) mechanism was proposed previously, its fluorescence-enhanced effect still remains somewhat ambiguous, according to unknown influences of non-radiative energy decay pathways, such as intersystem crossing and internal conversion. Herein, a thorough study using density functional theory has been performed for low-lying electronic states of the ADPA monomer and hydrated ADPA-Zn2+ complex. Based on interfragment charge transfer analyses, we quantitatively calculated the amount of transferred electrons in the monomer and complex, providing solid evidences for the PET mechanism and in line with the conclusion of frontier molecular orbital analyses. Moreover, the ISC process of S1→T2 was confirmed to play a considerable role in the excitation energy relaxation process of the ADPA monomer, but this influence was significantly suppressed in the hydrated ADPA-Zn2+ complex. These results provide additional clues for the design of new metal ion-specific fluorescence probes.

MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control.

HCl/DMSO/HFIP-Mediated Chlorination of Pyrrolo[2,1-a]isoquinolines and Other Electron-Rich Heteroarenes.

An efficient oxidative chlorination of pyrrolo[2,1-a]isoquinolines has been established using HCl (aq) as the chlorine source and DMSO as the terminal oxidant in HFIP at ambient temperature. A variety of chlorinated pyrrolo[2,1-a]isoquinoline derivatives have been prepared readily in 23 to 99% yields. This chlorination strategy can be expanded to the functionalization of other electron-rich heteroarenes including substituted pyrroles, indoles, and naphthols.

Regioselective 1,4-/1,3-Difunctionalization of 1,3-Enynes with Selenosulfonates in Water.

1,4-/1,3-Regioselective bifunctionalization of 1,3-enynes with selenosulfonates in water under catalyst-free conditions for the construction of sulfonyl allene and 1,3-disulfonyl-conjugated dienes respectively have been developed. The reactions feature mild reaction conditions in aqueous solution and remarkable regioselectivity controlled by substrates.

Binding Strengths and Orientations in CO2 Adsorption on Cationic Scandium Oxides: Governing Factor Revealed by a Combined Infrared Spectroscopy and Theoretical Study.

Carbon dioxide (CO2) adsorption is a critical step to curbing carbon emissions from fossil fuel combustion. Among various options, transition metal oxides have received extensive attention as promising CO2 adsorbents due to their affordability and sustainability for large-scale use. Here, the nature of binding interactions between CO2 molecules and cationic scandium oxides of different sizes, i.e., ScO+, Sc2O2+, and Sc3O4+, is investigated by mass-selective infrared photodissociation spectroscopy combined with quantum chemical calculations. The well-accepted electrostatic considerations failed to provide explanations for the trend in the binding strengths and variations in the binding orientations between CO2 and metal sites of cationic scandium oxides. The importance of orbital interactions in the driving forces for CO2 adsorption on cationic scandium oxides was revealed by energy decomposition analyses. A molecular surface property, known as the local electron attachment energy, is introduced to elucidate the binding affinity and orientation-specific reactivity of cationic scandium oxides upon the CO2 attachment. This study not only reveals the governing factor in the binding behaviors of CO2 adsorption on cationic scandium oxides but also serves as an archetype for predicting and rationalizing favorable binding sites and orientations in extended surface-adsorbate systems.

Structural Study of [Sc3O4(CO2)n]+ (n = 2, 3) Complexes by Infrared Photodissociation Spectroscopy and Density Functional Calculations.

The catalytic transformation of CO2 into valuable products has garnered wide interest owing to both economic and environmental benefits, in which the chemical fixation of CO2 into carbonate structures represents a crucial step that occurs on the adsorbed catalyst surfaces. Transition metal oxides with acidic and basic active sites have exhibited potential in promoting the carbonation of weakly bound CO2 molecules. Here, the interactions between CO2 molecules and the Sc3O4+ cation in the gas phase are investigated by using infrared photodissociation spectroscopy in conjunction with quantum chemical calculations. Both end-on and various carbonate-containing configurations, including center and bridge carbonate structures, have been theoretically identified for the CO2-coordinated ion-molecule complexes. Based on the comparison between the experimental spectra and simulated spectra of low-lying isomers in the CO2 antisymmetric stretching vibrational frequency region, isomers characterized by a bridge carbonate core structure are demonstrated to be the major contributors to the observed spectra. Examination of potential energy surfaces reveals lower energy barriers and simpler reaction routes for the conversion of molecularly bound CO2 into a bridge carbonate moiety, providing reasonable explanations for their prevalence in the experiments.

Factors influencing the implementation of early discharge hospital at home and admission avoidance hospital at home: a qualitative evidence synthesis.

BACKGROUND: Worldwide there is an increasing demand for Hospital at Home as an alternative to hospital admission. Although there is a growing evidence base on the effectiveness and cost-effectiveness of Hospital at Home, health service managers, health professionals and policy makers require evidence on how to implement and sustain these services on a wider scale. OBJECTIVES: (1) To identify, appraise and synthesise qualitative research evidence on the factors that influence the implementation of Admission Avoidance Hospital at Home and Early Discharge Hospital at Home, from the perspective of multiple stakeholders, including policy makers, health service managers, health professionals, patients and patients' caregivers. (2) To explore how our synthesis findings relate to, and help to explain, the findings of the Cochrane intervention reviews of Admission Avoidance Hospital at Home and Early Discharge Hospital at Home services. SEARCH METHODS: We searched MEDLINE, CINAHL, Global Index Medicus and Scopus until 17 November 2022. We also applied reference checking and citation searching to identify additional studies. We searched for studies in any language. SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with qualitative data collection and analysis methods examining the implementation of new or existing Hospital at Home services from the perspective of different stakeholders. DATA COLLECTION AND ANALYSIS: Two authors independently selected the studies, extracted study characteristics and intervention components, assessed the methodological limitations using the Critical Appraisal Skills Checklist (CASP) and assessed the confidence in the findings using GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research). We applied thematic synthesis to synthesise the data across studies and identify factors that may influence the implementation of Hospital at Home. MAIN RESULTS: From 7535 records identified from database searches and one identified from citation tracking, we included 52 qualitative studies exploring the implementation of Hospital at Home services (31 Early Discharge, 16 Admission Avoidance, 5 combined services), across 13 countries and from the perspectives of 662 service-level staff (clinicians, managers), eight systems-level staff (commissioners, insurers), 900 patients and 417 caregivers. Overall, we judged 40 studies as having minor methodological concerns and we judged 12 studies as having major concerns. Main concerns included data collection methods (e.g. not reporting a topic guide), data analysis methods (e.g. insufficient data to support findings) and not reporting ethical approval. Following synthesis, we identified 12 findings graded as high (n = 10) and moderate (n = 2) confidence and classified them into four themes: (1) development of stakeholder relationships and systems prior to implementation, (2) processes, resources and skills required for safe and effective implementation, (3) acceptability and caregiver impacts, and (4) sustainability of services. AUTHORS' CONCLUSIONS: Implementing Admission Avoidance and Early Discharge Hospital at Home services requires early development of policies, stakeholder engagement, efficient admission processes, effective communication and a skilled workforce to safely and effectively implement person-centred Hospital at Home, achieve acceptance by staff who refer patients to these services and ensure sustainability. Future research should focus on lower-income country and rural settings, and the perspectives of systems-level stakeholders, and explore the potential negative impact on caregivers, especially for Admission Avoidance Hospital at Home, as this service may become increasingly utilised to manage rising visits to emergency departments.

Clinical application of repetitive transcranial magnetic stimulation in improving functional impairments post-stroke: review of the current evidence and potential challenges.

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.

Balance Control Deficits are Associated With Diminished Ankle Force Sense, Not Position Sense, in Athletes with Chronic Ankle Instability.

OBJECTIVES: To compare balance control and ankle proprioception between athletes with and without chronic ankle instability (CAI). A further objective was to explore the relationship between balance control performance and ankle proprioception in athletes with CAI. DESIGN: Cross-sectional study. SETTINGS: Sports Rehabilitation Laboratory. PARTICIPANTS: Eighty-eight recreational athletes (47 CAI and 41 healthy control) were recruited. INTERVENTIONS: No applicable. MAIN OUTCOME MEASURES: Balance control performance was assessed using the sway velocity of the center of the pressure during the one-leg standing tasks. Ankle proprioception, including joint position sense and force sense, were tested using absolute error (AE) associated with joint position reproduction and force reproduction tasks in 4 directions, that is, plantarflexion, dorsiflexion, inversion, and eversion. RESULTS: Athletes with CAI performed significantly worse than those without CAI in balance control tasks. In addition, CAI athletes showed significantly worse joint position sense and force sense in all 3 movement directions tested (plantarflexion, inversion, and eversion). Correlation analysis showed that the AE of the plantarflexion force sense was significantly moderately correlated with medial-lateral sway velocity in the one-leg standing with eyes open and closed conditions (r=.372-.403, P=.006-.012), and the AE of inversion force sense was significantly moderately correlated with medial-lateral sway velocity in the one-leg standing with eyes open (r=.345, P=.018) in athletes with CAI, but the joint position sense measures were not (all P>0.05). CONCLUSIONS: Athletes with CAI showed significantly impaired balance control performance and diminished ankle proprioception. Deficit in force sense was deemed as a moderate predictor of one-leg standing balance control deficits in athletes with dominant-side injury CAI, whereas ankle position sense may be a small predictor.

Physical therapy for acute and sub-acute low back pain: A systematic review and expert consensus.

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.

Simultaneous inoculation of non-Saccharomyces yeast and lactic acid bacteria for aromatic kiwifruit wine production.

To further explore strain potential and develop an aromatic kiwifruit wine fermentation technique, the feasibility of simultaneous inoculation by non-Saccharomyces yeast and lactic acid bacteria was investigated. Lacticaseibacillus paracasei, Lactiplantibacillus plantarum, and Limosilactobacillus fermentum, which have robust ß-glucosidase activity as well as good acid and ethanol tolerance, were inoculated for simultaneous fermentation with Zygosaccharomyces rouxii and Meyerozyma guilliermondii, respectively. Subsequently, the chemical compositions and sensory characteristics of the wines were comprehensively evaluated. The results showed that the majority of the simultaneous protocols effectively improved the quality of kiwifruit wines, increasing the content of polyphenols and volatile compounds, thereby enhancing sensory acceptability compared to the fermentation protocols inoculated with non-Saccharomyces yeast individually. Particularly, the collaboration between Lacp. plantarum and Z. rouxii significantly increased the diversity and content of esters, alcohols, and ketones, intensifying floral and seeded fruit odors, and achieving the highest overall acceptability. This study highlights the potential significance of simultaneous inoculation in kiwifruit wine production.

The Effectiveness of Low-dose Esmketamine Versus Remifentanil Adjunct to Propofol for Sedation in Patients Undergoing Radiofrequency Thermocoagulation for Trigeminal Neuralgia.

Objectives: To access the effectiveness of propofol-esketamine versus propofol-remifentanyl in patients undergoing radiofrequency Thermocoagulation for Trigeminal Neuralgia of gasserian ganglion. Methods: In this clinical trial, 80 patients were candidates for RFT were randomly divided into two groups (n= 40). These patients aged from 21 to 81 years old. Before the start of the procedure, both groups received propofol TCI with a target level of 1.5 µgml-1. The intervention group (group E) received esketamine 0.15 mgkg-1, and the control group (group R) received remifentanyl 1.0 µgkg-1. The patients, the anesthetists and the surgeons were unaware of the medication regimen. Sedation level (based on a MOAA/S), blood pressure, oxygen saturation, the dosage of propofol, recovery time (based on Aldrete scores), postoperation pain (based on NRS), surgeons and patient satisfaction, and Pittsburgh Sleep Quality Index (PQSI) were recorded. Results: Data from 80 patients were analyzed. The sedative effects were equal in the two groups (P = .680) and the MOAA/s scores of both groups were basically maintained at or below 2 points, however, the dosage of propofol in group E was significantly less than that in group R [5.3mgkg-1h-1 (5.0 to 5.7) vs 5.8 mgkg-1h-1 ( 5.3 to 6.3), P = .000]. The group E had higher blood pressure levels during the procedure (PSBP = .002, PDBP = .023). Surgeons and patient satisfaction (Ps = .164, Pp = .580), recovery time (P = .228),The NRS values after 24hrs (P = .777)and PQSI showed no significant differences between the two groups (P = .133). Conclusions: Low-dose esketamine reduces the total amount of propofol necessary for sedation and incidence of respiratory depression during RFT of gasserian ganglion in American Society of Anesthesiologists I to III patients without affecting recovery time, satisfaction of surgeons and patients, cardiovascular adverse events, when compared with remifentanil.

Adolescents and Children Age Estimation Using Machine Learning Based on Pulp and Tooth Volumes on CBCT Images.

OBJECTIVES: To estimate adolescents and children age using stepwise regression and machine learning methods based on the pulp and tooth volumes of the left maxillary central incisor and cuspid on cone beam computed tomography (CBCT) images, and to compare and analyze the estimation results. METHODS: A total of 498 Shanghai Han adolescents and children CBCT images of the oral and maxillofacial regions were collected. The pulp and tooth volumes of the left maxillary central incisor and cuspid were measured and calculated. Three machine learning algorithms (K-nearest neighbor, ridge regression, and decision tree) and stepwise regression were used to establish four age estimation models. The coefficient of determination, mean error, root mean square error, mean square error and mean absolute error were computed and compared. A correlation heatmap was drawn to visualize and the monotonic relationship between parameters was visually analyzed. RESULTS: The K-nearest neighbor model (R2=0.779) and the ridge regression model (R2=0.729) outperformed stepwise regression (R2=0.617), while the decision tree model (R2=0.494) showed poor fitting. The correlation heatmap demonstrated a monotonically negative correlation between age and the parameters including pulp volume, the ratio of pulp volume to hard tissue volume, and the ratio of pulp volume to tooth volume. CONCLUSIONS: Pulp volume and pulp volume proportion are closely related to age. The application of CBCT-based machine learning methods can provide more accurate age estimation results, which lays a foundation for further CBCT-based deep learning dental age estimation research.

Lateral Shuffle-Induced Fatigue Effects on Ankle Proprioception and Countermovement Jump Performance.

To determine how lateral shuffling/lateral shuffle (LS) -induced fatigue affects ankle proprioception and countermovement jump (CMJ) performance. Eighteen male college athletes performed 6 modes of a repeated LS protocol with 2 distances (2.5 and 5 m) and 3 speeds (1.6, 1.8, and 2.0 m/s). After LS, ankle inversion proprioception (AIP) was measured using the active movement extent discrimination apparatus (AMEDA). CMJ, blood lactate (BLa), heart rate (HR) and rating of perceived exertion (RPE) were measured before and after LS. The number of changes of direction (CODs) in each protocol was recorded. LS-induced fatigue was evident in BLa, HR and RPE (all p < 0.05), increasing with shorter shuffle distance and faster speed. RM-ANOVA showed a significant distance main effect on both AIP (p < 0.01) and CMJ (p < 0.05), but the speed main effect was only significant for CMJ (p ≤ 0.001), not AIP (p = 0.87). CMJ performance was correlated with BLa, HR and RPE (r values range from -0.62 to -0.32, all p ≤ 0.001). AIP was only correlated with CODs (r = -0.251, p < 0.01). These results suggested that in LS, shorter distance, regardless of speed, was associated with worse AIP, whereas subsequent CMJ performance was affected by both LS distance and speed. Hence, AIP performance was not related to physiological fatigue, but CMJ performance was. Results imply that LS affects processing proprioceptive input and producing muscular output differently, and that these two aspects of neuromuscular control are affected by physiological fatigue to varying degrees. These findings have implications for injury prevention and performance enhancement.

Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein.

Japanese encephalitis is a mosquito-borne disease caused by the Japanese encephalitis virus (JEV) that is prevalent in Asia and the Western Pacific. Currently, there is no effective treatment for Japanese encephalitis. Curcumin (Cur) is a compound extracted from the roots of Curcuma longa, and many studies have reported its antiviral and anti-inflammatory activities. However, the high cytotoxicity and very low solubility of Cur limit its biomedical applications. In this study, Cur carbon quantum dots (Cur-CQDs) were synthesized by mild pyrolysis-induced polymerization and carbonization, leading to higher water solubility and lower cytotoxicity, as well as superior antiviral activity against JEV infection. We found that Cur-CQDs effectively bound to the E protein of JEV, preventing viral entry into the host cells. In addition, after continued treatment of JEV with Cur-CQDs, a mutant strain of JEV was evolved that did not support binding of Cur-CQDs to the JEV envelope. Using transmission electron microscopy, biolayer interferometry, and molecular docking analysis, we revealed that the S123R and K312R mutations in the E protein play a key role in binding Cur-CQDs. The S123 and K312 residues are located in structural domains II and III of the E protein, respectively, and are responsible for binding to receptors on and fusing with the cell membrane. Taken together, our results suggest that the E protein of flaviviruses represents a potential target for the development of CQD-based inhibitors to prevent or treat viral infections.