The deep population history of northern East Asia from the Late Pleistocene to the Holocene.

Northern East Asia was inhabited by modern humans as early as 40 thousand years ago (ka), as demonstrated by the Tianyuan individual. Using genome-wide data obtained from 25 individuals dated to 33.6-3.4 ka from the Amur region, we show that Tianyuan-related ancestry was widespread in northern East Asia before the Last Glacial Maximum (LGM). At the close of the LGM stadial, the earliest northern East Asian appeared in the Amur region, and this population is basal to ancient northern East Asians. Human populations in the Amur region have maintained genetic continuity from 14 ka, and these early inhabitants represent the closest East Asian source known for Ancient Paleo-Siberians. We also observed that EDAR V370A was likely to have been elevated to high frequency after the LGM, suggesting the possible timing for its selection. This study provides a deep look into the population dynamics of northern East Asia.

The intrinsically disordered CARDs-Helicase linker in RIG-I is a molecular gate for RNA proofreading.

The innate immune receptor RIG-I provides a first line of defense against viral infections. Viral RNAs are recognized by RIG-I's C-terminal domain (CTD), but the RNA must engage the helicase domain to release the signaling CARD (Caspase Activation and Recruitment Domain) domains from their autoinhibitory CARD2:Hel2i interactions. Because the helicase itself lacks RNA specificity, mechanisms to proofread RNAs entering the helicase domain must exist. Although such mechanisms would be crucial in preventing aberrant immune responses by non-specific RNAs, they remain largely uncharacterized to date. This study reveals a previously unknown proofreading mechanism through which RIG-I ensures that the helicase engages RNAs explicitly recognized by the CTD. A crucial part of this mechanism involves the intrinsically disordered CARDs-Helicase Linker (CHL), which connects the CARDs to the helicase subdomain Hel1. CHL uses its negatively charged regions to antagonize incoming RNAs electrostatically. In addition to this RNA gating function, CHL is essential for stabilization of the CARD2:Hel2i interface. Overall, we uncover that the CHL and CARD2:Hel2i interface work together to establish a tunable gating mechanism that allows CTD-chosen RNAs to bind the helicase domain, while at the same time blocking non-specific RNAs. These findings also indicate that CHL could represent a novel target for RIG-I-based therapeutics.

Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndromes (IVUS-ACS): a two-stage, multicentre, randomised trial.

BACKGROUND: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome. METHODS: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups. INTERPRETATION: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Upregulated Expression of the IL-9 Receptor on TRAF3-Deficient B Lymphocytes Confers Ig Isotype Switching Responsiveness to IL-9 in the Presence of Antigen Receptor Engagement and IL-4.

The pleiotropic cytokine IL-9 signals to target cells by binding to a heterodimeric receptor consisting of the unique subunit IL-9R and the common subunit γ-chain shared by multiple cytokines of the γ-chain family. In the current study, we found that the expression of IL-9R was strikingly upregulated in mouse naive follicular B cells genetically deficient in TNFR-associated factor 3 (TRAF3), a critical regulator of B cell survival and function. The highly upregulated IL-9R on Traf3-/- follicular B cells conferred responsiveness to IL-9, including IgM production and STAT3 phosphorylation. Interestingly, IL-9 significantly enhanced class switch recombination to IgG1 induced by BCR crosslinking plus IL-4 in Traf3-/- B cells, which was not observed in littermate control B cells. We further demonstrated that blocking the JAK-STAT3 signaling pathway abrogated the enhancing effect of IL-9 on class switch recombination to IgG1 induced by BCR crosslinking plus IL-4 in Traf3-/- B cells. Our study thus revealed, to our knowledge, a novel pathway that TRAF3 suppresses B cell activation and Ig isotype switching by inhibiting IL-9R-JAK-STAT3 signaling. Taken together, our findings provide (to our knowledge) new insights into the TRAF3-IL-9R axis in B cell function and have significant implications for the understanding and treatment of a variety of human diseases involving aberrant B cell activation such as autoimmune disorders.

Assembly and comparative analysis of the complete mitochondrial genome of Fritillaria ussuriensis Maxim. (Liliales: Liliaceae), an endangered medicinal plant.

BACKGROUND: Fritillaria ussuriensis is an endangered medicinal plant known for its notable therapeutic properties. Unfortunately, its population has drastically declined due to the destruction of forest habitats. Thus, effectively protecting F. ussuriensis from extinction poses a significant challenge. A profound understanding of its genetic foundation is crucial. To date, research on the complete mitochondrial genome of F. ussuriensis has not yet been reported. RESULTS: The complete mitochondrial genome of F. ussuriensis was sequenced and assembled by integrating PacBio and Illumina sequencing technologies, revealing 13 circular chromosomes totaling 737,569 bp with an average GC content of 45.41%. A total of 55 genes were annotated in this mitogenome, including 2 rRNA genes, 12 tRNA genes, and 41 PCGs. The mitochondrial genome of F. ussuriensis contained 192 SSRs and 4,027 dispersed repeats. In the PCGs of F. ussuriensis mitogenome, 90.00% of the RSCU values exceeding 1 exhibited a preference for A-ended or U-ended codons. In addition, 505 RNA editing sites were predicted across these PCGs. Selective pressure analysis suggested negative selection on most PCGs to preserve mitochondrial functionality, as the notable exception of the gene nad3 showed positive selection. Comparison between the mitochondrial and chloroplast genomes of F. ussuriensis revealed 20 homologous fragments totaling 8,954 bp. Nucleotide diversity analysis revealed the variation among genes, and gene atp9 was the most notable. Despite the conservation of GC content, mitogenome sizes varied significantly among six closely related species, and colinear analysis confirmed the lack of conservation in their genomic structures. Phylogenetic analysis indicated a close relationship between F. ussuriensis and Lilium tsingtauense. CONCLUSIONS: In this study, we sequenced and annotated the mitogenome of F. ussuriensis and compared it with the mitogenomes of other closely related species. In addition to genomic features and evolutionary position, this study also provides valuable genomic resources to further understand and utilize this medicinal plant.

PCSK9 inhibitor added to high-intensity statin therapy to prevent cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention: a randomized, double- blind, placebo-controlled, multicenter SHAWN study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Leukemia inhibitory factor protects against graft-versus-host disease while preserving graft-versus-leukemia activity.

Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation, a widely used therapy for hematologic malignancies and blood disorders. Here, we report an unexpected role of cytokine leukemia inhibitory factor (LIF) in protecting against GVHD development. Administrating recombinant LIF protein (rLIF) protects mice from GVHD-induced tissue damage and lethality without compromising the graft-versus-leukemia activity, which is crucial to prevent tumor relapse. We found that rLIF decreases the infiltration and activation of donor immune cells and protects intestinal stem cells to ameliorate GVHD. Mechanistically, rLIF downregulates IL-12-p40 expression in recipient dendritic cells after irradiation through activating STAT1 signaling, which results in decreased major histocompatibility complex II levels on intestinal epithelial cells and decreased donor T-cell activation and infiltration. This study reveals a previously unidentified protective role of LIF for GVHD-induced tissue pathology and provides a potential effective therapeutic strategy to limit tissue pathology without compromising antileukemic efficacy.

Exosomal lncRNA-MIAT promotes neovascularization via the miR-133a-3p/MMP-X1 axis in diabetic retinopathy.

Diabetic retinopathy (DR), a most common microangiopathy of diabetes, causes vision loss and even blindness. The mechanisms of exosomal lncRNA remain unclear in the development of DR. Here, we first identifed the pro-angiogenic effect of exosomes derived from vitreous humor of proliferative diabetic retinopathy patients, where lncRNA-MIAT was enriched inside. Secondly, lncRNA-MIAT was demonstrated significantly increased in exosomes from high glucose induced human retinal vascular endothelial cell, and can regulate tube formation, migration and proliferation ability to promote angiogenesis in vitro and in vivo. Mechanistically, the pro-angiogenic effect of lncRNA-MIAT was via the lncRNA-MIAT/miR-133a-3p/MMP-X1 axis. The reduced level of lncRNA-MIAT in this axis mitigated the generation of retinal neovascular in mouse model of oxygen-induced retinopathy (OIR), providing crucial evidence for lncRNA-MIAT as a potential clinical target. These findings enhance our understanding of the role of exosomal lncRNA-MIAT in retinal angiogenesis, and propose a promising therapeutic strategy against diabetic retinopathy.

Human lens epithelial-secreted exosomes attenuate ocular angiogenesis via inhibiting microglial activation.

The lens is an avascular tissue, where epithelial cells (LECs) are the primary living cells. The role of LECs-derived exosomes (LEC-exos) is largely unknown. In our study, we determined the anti-angiogenic role of LEC-exos, manifested as regressed retinal neovascularization (NV) using the oxygen-induced retinopathy (OIR), and reduced choroidal NV size and pathological vascular leakage using the laser-induced choroidal neovascularization (laser-induced CNV). Furthermore, the activation and accumulation of microglia were also restricted by LEC-exos. Based on Luminex multiplex assays, the expressions of chemokines such as SCYB16/CXCL16, MCP-1/CCL2, I-TAC/CXCL11, and MIP 3beta/CCL19 were decreased after treatment with LEC-exos. Transwell assays showed that LEC-exos restricted the migration of the mouse microglia cell line (BV2 cells). After incubation with LEC-exos-treated BV2 cells, human umbilical vein endothelial cells (hUVECs) were collected for further evaluation using tube formation, Transwell assays, and 5-ethynyl-2'-deoxyuridine (EDU) assays. Using in vitro experiments, the pro-angiogenic effect of microglia was restricted by LEC-exos. Hence, it was investigated that LEC-exos attenuated ocular NV, which might attribute to the inhibition of microglial activation and accumulation.

Lens epithelial cell-derived exosome inhibits angiogenesis in ocular pathological neovascularization through its delivery of miR-146a-5p.

Abnormal ocular neovascularization, a major pathology of eye diseases, leads to severe visual loss. The role of lens epithelial cell (LEC)-derived exosomes (Lec-exo) is largely unknown. Thus, we aimed to investigate whether Lec-exo can inhibit abnormal ocular neovascularization and explore the possible mechanisms. In our study, we proved the first evidence that exosomes derived from LECs attenuated angiogenesis in both oxygen-induced retinopathy and laser-induced choroidal neovascularization mice models. Further in vitro experiments proved that Lec-exo inhibited proliferation, migration, and tube formation capability of human umbilical vein endothelial cells in high glucose condition. Further high-throughput miRNAs sequencing analysis detected that miR-146a-5p was enriched in Lec-exo. Mechanistically, exosomal miR-146a-5p was delivered to endothelial cells and bound to the NRAS coding sequence, which subsequently inactivated AKT/ERK signaling pathway. We successfully elucidated the function of Lec-exo in inhibiting abnormal ocular neovascularization, which may offer a promising strategy for treatment of abnormal ocular neovascularization.

Effect of small molecular crowders on dynamics of kinesin molecular motors.

Kinesin is a motor protein that can convert chemical energy of ATP hydrolysis into mechanical energy of moving processively on microtubules. Apart from the load and ATP concentration affecting the dynamics of the motor such as velocity, run length, dissociation rate, etc., the increase of solution viscosity by supplementing crowding agents of low molecular weight into the buffer can also affect the dynamics. Here, based on our proposed model for the chemomechanical coupling of the kinesin motor, a systematically theoretical study of the motor dynamics under the variation of the viscosity and load is presented. Both the load on the motor's stalk and that on one of the two heads are considered. The theoretical results provide a consistent explanation of the available contradictory experimental results, with some showing that increasing viscosity decreases sensitively the velocity whereas others showing that increasing viscosity has little effect on the velocity. The theoretical results reproduce quantitatively the puzzling experimental data showing that under different directions of the load on the stalk, increasing viscosity has very different effects on the change of run length or dissociation rate. The theoretical results predict that in both the pure and crowded buffers the dependence of the run length on the load acting one of the two heads has very different feature from that on the load acting on the stalk.

Modeling study of kinesin-13 MCAK microtubule depolymerase.

Mitotic centromere-associated kinesin (MCAK) motor protein is a typical member of the kinesin-13 family, which can depolymerize microtubules from both plus and minus ends. A critical issue for the MCAK motor is how it performs the depolymerase activity. To address the issue, the pathway of the MCAK motor moving on microtubules and depolymerizing the microtubules is presented here. On the basis of the pathway, the dynamics of both the wild-type and mutant MCAK motors is studied theoretically, which include the full-length MCAK, the full-length MCAK with mutations in the α4-helix of the motor domain, the mutant full-length MCAK with a neutralized neck, the monomeric MCAK and the mutant monomeric MCAK with a neutralized neck. The studies show that a single dimeric MCAK motor can depolymerize microtubules in a processive manner, with either one tubulin or two tubulins being removed per times. The theoretical results are in agreement with the available experimental data. Moreover, predicted results are provided.

Leveraging External Aggregated Information for the Marginal Accelerated Failure Time Model.

It is becoming increasingly common for researchers to consider leveraging information from external sources to enhance the analysis of small-scale studies. While much attention has focused on univariate survival data, correlated survival data are prevalent in epidemiological investigations. In this article, we propose a unified framework to improve the estimation of the marginal accelerated failure time model with correlated survival data by integrating additional information given in the form of covariate effects evaluated in a reduced accelerated failure time model. Such auxiliary information can be summarized by using valid estimating equations and hence can then be combined with the internal linear rank-estimating equations via the generalized method of moments. We investigate the asymptotic properties of the proposed estimator and show that it is more efficient than the conventional estimator using internal data only. When population heterogeneity exists, we revise the proposed estimation procedure and present a shrinkage estimator to protect against bias and loss of efficiency. Moreover, the proposed estimation procedure can be further refined to accommodate the non-negligible uncertainty in the auxiliary information, leading to more trustable inference conclusions. Simulation results demonstrate the finite sample performance of the proposed methods, and empirical application on the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial substantiates its practical relevance.

Population asynchrony within and between trophic levels have contrasting effects on consumer community stability in a subtropical lake.

Clarifying the effects of biodiversity on ecosystem stability in the context of global environmental change is crucial for maintaining ecosystem functions and services. Asynchronous changes between trophic levels over time (i.e. trophic community asynchrony) are expected to increase trophic mismatch and alter trophic interactions, which may consequently alter ecosystem stability. However, previous studies have often highlighted the stabilising mechanism of population asynchrony within a single trophic level, while rarely examining the mechanism of trophic community asynchrony between consumers and their food resources. In this study, we analysed the effects of population asynchrony within and between trophic levels on community stability under the disturbances of climate warming, fishery decline and de-eutrophication, based on an 18-year monthly monitoring dataset of 137 phytoplankton and 91 zooplankton in a subtropical lake. Our results showed that species diversity promoted community stability mainly by increasing population asynchrony both for phytoplankton and zooplankton. Trophic community asynchrony had a significant negative effect on zooplankton community stability rather than that of phytoplankton, which supports the match-mismatch hypothesis that trophic mismatch has negative effects on consumers. Furthermore, the results of the structural equation models showed that warming and top-down effects may simultaneously alter community stability through population dynamics processes within and between trophic levels, whereas nutrients act on community stability mainly through the processes within trophic levels. Moreover, we found that rising water temperature decreased trophic community asynchrony, which may challenge the prevailing idea that climate warming increases the trophic mismatch between primary producers and consumers. Overall, our study provides the first evidence that population and trophic community asynchrony have contrasting effects on consumer community stability, which offers a valuable insight for addressing global environmental change.

M2 microglia-derived exosomes promote vascular remodeling in diabetic retinopathy.

Diabetic retinopathy (DR) is a vision-threatening diabetic complication that is characterized by microvasculature impairment and immune dysfunction. The present study demonstrated that M2 microglia intensively participated in retinal microangiopathy in human diabetic proliferative membranes, mice retinas, retinas of mice with oxygen-induced retinopathy (OIR) mice, and retinas of streptozotocin-induced DR mice. Further in vivo and in vitro experiments showed that exosomes derived from M2 polarized microglia (M2-exo) could reduce pericyte apoptosis and promote endothelial cell proliferation, thereby promoting vascular remodeling and reducing vascular leakage from the diabetic retina. These effects were further enhanced by M2-exo that facilitated M2 polarization of retinal microglia. Collectively, the study demonstrated the capability of M2-exo to induce retinal microvascular remodeling, which may provide a new therapeutic strategy for the treatment of DR.

Biological ultrathin amniotic membrane flap to close refractory macular holes associated with high myopia.

PURPOSE: To propose an ultrathin biological amniotic membrane (btAM) thinner than 10 µm as the graft to treat highly myopic macular holes (MH). METHODS: This pilot study included 14 patients affected by refractory macular holes associated with high myopia. btAM was used as a bandage covering the holes. The best-corrected visual acuity (BCVA), fundus photography, and optical coherence tomography (OCT) before and after surgery were compared. RESULTS: The mean MH size was 865.93 ± 371.72 µm and all the MHs achieved anatomical closure. The btAM located centrally and fully on MHs from fundus photography yet no obvious visual masking was complained. The average BCVA 1 month, 3, and 6 months after surgery were 0.95 ± 0.24, 0.92 ± 0.23, 0.92 ± 0.23 logMAR, respectively, improved significantly compared to pre-operative BCVA (1.24 ± 0.42 logMAR, all P < 0.05). Ten out of 14 (71.4%) exhibited 2C closure patterns (formally closed and no bare RPE) on OCT. CONCLUSION: The btAM thinner showed a favorable anatomical success with less risk of parafoveal atrophy or iatrogenic injuries and shortened the dissolving time.

Using QCT for the prediction of spontaneous age- and gender-specific thoracolumbar vertebral fractures and accompanying distant vertebral fractures.

PURPOSE: To investigate the value and age- and gender-specific threshold values of bone mineral density (BMD) by quantitative computed tomography (QCT) for the prediction of spontaneous thoracolumbar vertebral fractures and thoracolumbar junction fractures accompanying distant vertebral fractures. METHODS: Among the 556 patients included, 68 patients had thoracolumbar vertebral fractures (12 patients with distant vertebral fractures, 56 patients without distant vertebral fractures) and 488 patients had no vertebral fractures. All patients were grouped by gender and age. According to the principle of Youden index, the threshold values were calculated from receiver operating characteristic (ROC) curves. RESULTS: The threshold values for predicting thoracolumbar vertebral fractures were 89.8 mg/cm3 for all subjects, 90.1 mg/cm3 for men, and 88.6 mg/cm3 for women. The threshold values for men aged < 60 years old and ≥ 60 years old were 117.4 mg/cm3 and 87.5 mg/cm3, respectively. The threshold values for women aged < 60 years old and ≥ 60 years old were 88.6 and 68.4 mg/cm3, respectively. The threshold value for predicting spontaneous thoracolumbar junction fractures with distant vertebral fractures was 62.7 mg/cm3. CONCLUSIONS: QCT provides a good ability to predict age- and gender-specific spontaneous thoracolumbar vertebral fractures, and to further predict spontaneous thoracolumbar junction fractures with distant vertebral fractures.

Muscle Synergy during Wrist Movements Based on Non-Negative Tucker Decomposition.

Modular control of the muscle, which is called muscle synergy, simplifies control of the movement by the central nervous system. The purpose of this study was to explore the synergy in both the frequency and movement domains based on the non-negative Tucker decomposition (NTD) method. Surface electromyography (sEMG) data of 8 upper limb muscles in 10 healthy subjects under wrist flexion (WF) and wrist extension (WE) were recorded. NTD was selected for exploring the multi-domain muscle synergy from the sEMG data. The results showed two synergistic flexor pairs, Palmaris longus-Flexor Digitorum Superficialis (PL-FDS) and Extensor Carpi Radialis-Flexor Carpi Radialis (ECR-FCR), in the WF stage. Their spectral components are mainly in the respective bands 0-20 Hz and 25-50 Hz. And the spectral components of two extensor pairs, Extensor Digitorum-Extensor Carpi Ulnar (ED-ECU) and Extensor Carpi Radialis-Brachioradialis (ECR-B), are mainly in the respective bands 0-20 Hz and 7-45 Hz in the WE stage. Additionally, further analysis showed that the Biceps Brachii (BB) muscle was a shared muscle synergy module of the WE and WF stage, while the flexor muscles FCR, PL and FDS were the specific synergy modules of the WF stage, and the extensor muscles ED, ECU, ECR and B were the specific synergy modules of the WE stage. This study showed that NTD is a meaningful method to explore the multi-domain synergistic characteristics of multi-channel sEMG signals. The results can help us to better understand the frequency features of muscle synergy and shared and specific synergies, and expand the study perspective related to motor control in the nervous system.

Hand Gesture Recognition Based on High-Density Myoelectricity in Forearm Flexors in Humans.

Electromyography-based gesture recognition has become a challenging problem in the decoding of fine hand movements. Recent research has focused on improving the accuracy of gesture recognition by increasing the complexity of network models. However, training a complex model necessitates a significant amount of data, thereby escalating both user burden and computational costs. Moreover, owing to the considerable variability of surface electromyography (sEMG) signals across different users, conventional machine learning approaches reliant on a single feature fail to meet the demand for precise gesture recognition tailored to individual users. Therefore, to solve the problems of large computational cost and poor cross-user pattern recognition performance, we propose a feature selection method that combines mutual information, principal component analysis and the Pearson correlation coefficient (MPP). This method can filter out the optimal subset of features that match a specific user while combining with an SVM classifier to accurately and efficiently recognize the user's gesture movements. To validate the effectiveness of the above method, we designed an experiment including five gesture actions. The experimental results show that compared to the classification accuracy obtained using a single feature, we achieved an improvement of about 5% with the optimally selected feature as the input to any of the classifiers. This study provides an effective guarantee for user-specific fine hand movement decoding based on sEMG signals.

Practical gram-scale synthesis of bicyclol metabolites M2 and M3.

Bicyclol, an innovative hepatoprotective drug, was approved by the Chinese National Medical Products Administration (NMPA) in 2001 to treat Hepatitis B and drug-induced liver injury. Two active metabolites of bicyclol have been identified as M2 and M3. To evaluate the impact on drug safety and efficacy of possible drug-drug interactions (DDIs) associated with these metabolites, a sufficient quantity of these metabolites is required. Herein, we report a concise novel route for the synthesis of M2 and M3 using the Suzuki-Miyaura coupling as the key step. Furthermore, we complete the gram-scale syntheses of M2 and M3.