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The vast humid regions in southeast China are strongly influenced by the East Asian Monsoon (EAM); however, the origin and underlying mechanisms driving the EAM in this area remains uncertain. Here, we present Eocene palynological records from two sedimentary successions in the Qingjiang Basin of central Jiangxi Province, southeast China, which reveals a major vegetation transition from an early Eocene Ephedra -dominated shrub desert to late Eocene taxodioid Cupressaceae-dominated swamp forests. Using the Coexistence Approach and the Climatic Amplitude method, we quantitatively reconstructed climatic parameters, which indicate a climate shift from arid conditions with mean annual precipitation (MAP) lower than 200 mm to humid conditions with a MAP of 1479 ± 373 mm. We infer that this sharp increase in humidity is linked to the onset of a modern-style EAM, implying that the EAM has prevailed in southeast China since at least the late Eocene, much earlier than previously thought. We conclude that the establishment of the EAM in southeast China by the late Eocene was primarily controlled by paleogeographic changes, not changes in atmospheric CO 2 levels. These results provide a new perspective on the early evolutionary history of the EAM, and challenges the prevailing view that the origin of humid southeast China was a Neogene phenomenon. [Display omitted] • Vegetation changed from early Eocene desert to late Eocene swamp forests. • Eocene climate transformation from arid to humid monsoonal. • Quantitative estimates show the MAP increased from 200 mm to 1479 mm. • Modern-like EAM has prevailed in southeast China since at least the late Eocene. [ABSTRACT FROM AUTHOR]

The Paleocene–Eocene Thermal Maximum (PETM, ~56 Ma) was a geologically abrupt and extreme global warming event that had a profound effect on global climate and ecosystems. Efforts to understand the response of vegetation to this hyperthermal event have hitherto primarily focused on Europe and North America. However, a limited record from China hampers the understanding of regional terrestrial ecosystem response to PETM warming. Here, we present the a detailed palynological record from the Fushun Basin, NE China, spanning the late Paleocene to early Eocene. The palynological assemblage reveals an abrupt change in vegetation composition as a response to PETM warming. Swamps dominated by taxodioid conifers (Cupressaceae) were abruptly replaced by communities of Pinaceae conifers and the megathermal genus Aquilapollenites. This marked the abrupt collapse of the swamp ecosystem during the PETM as climate became hotter and wetter and mean annual temperature (MAT) increased from 15.6 °C to 19.7 °C. Vegetation turnover was driven by rapid global warming and localised changes due to increases in precipitation, subsequent elevated water levels, and expansion of lake systems. The marked discrepancy in the characteristics and magnitudes of the respective vegetation responses shows that the effects of PETM warming were more severe for swamp ecosystems than for other terrestrial ecosystems. The PETM warming led to swamp degradation, frequent wildfires, and concomitant peat burning; these changes may have triggered further warming through positive feedback mechanisms. • A detailed PETM palynological record in China was obtained. • Transient and abrupt change in vegetation composition during the PETM. • Abrupt collapse of swamp ecosystem in NE China during the PETM. • Quantitative estimates show the MAT increased from 15.6 to 19.7 °C. • Response of swamp ecosystem of NE China to PETM warming is remarkable. [ABSTRACT FROM AUTHOR]

The India–Asia collision and subsequent uplift of the Tibetan Plateau during the Cenozoic were the main drivers of Asian monsoon development and evolution. However, the climate and possible existence of a desert landscape in southern China prior to the significant uplift of the Tibetan Plateau remain uncertain, because of a lack of reliable proxies or direct geological evidence. The well–preserved early Eocene palynomorphs recovered from the Hengyang Basin, southern China, provide an ideal opportunity to address this problem. The palynological record suggests that the Hengyang Basin was dominated by xerophytic shrubs and an open forest vegetation landscape, confirming that a typical arid desert environment prevailed in the Hengyang Basin during the early Eocene. The high proportion of thermophilic and xerophytic taxa implies a hot and arid climate. The estimated mean annual precipitation (<230 mm) of the early Eocene in the Hengyang Basin was significantly lower than that of present (1354 mm). We propose that, prior to the significant uplift of the Tibetan Plateau, the combined effects of a strong subtropical anticyclone associated with the extremely warm climate and a rain–shadow effect caused by coastal mountains, were the primary factors responsible for the extreme arid climate and desert–like landscape of inland southern China during the early Eocene. • Early Eocene palynoflora was systematically studied in the Hengyang Basin. • Our result confirmed desert environment prevailed in southern China before the TP uplift. • The estimated MAP of the early Eocene in the Hengyang Basin was significantly lower than that of present. [ABSTRACT FROM AUTHOR]

The modern environment of southern China is dominated by a humid monsoon climate, and presents a striking contrast to the widespread deserts found at similar latitudes elsewhere. The formation of a monsoon climate marks a major environmental shift in southern China during the Cenozoic; however, the origin and possible driving mechanism of the climate transition remain unclear. Paleogene palynological records from seven basins across southern China offer an exceptional opportunity to address this knowledge gap. The Paleogene palynoflora reveals two completely different vegetation and climate patterns: the Paleocene to early Eocene was characterized by a relatively high abundance of xerophilous taxa, suggesting an arid/semi-arid climate; while the middle Eocene to Oligocene supported subtropical wet evergreen and deciduous broad-leaved mixed forest, characterized by a significant increase in broad-leaved, coniferous taxa and the almost complete disappearance of xerophilous taxa, together indicating the emergence of a warm–humid climate at this time. Combined palynological, sedimentological, paleozoological, and paleobotanical proxy evidence reveal that the major environmental transition occurred roughly around the middle Eocene; this transition may mark the establishment of the monsoon climate. Furthermore, middle Eocene climatic parameters obtained through the Coexistence Approach (CA) were compared with those of modern sites with known climate regimes. The middle Eocene parameters were most similar to those exposed to the modern East Asian Monsoon (EAM), further indicating that the middle Eocene climate of southern China was predominantly influenced by the EAM. The evolution of the Paleogene palynoflora in southern China is largely consistent with global climate change. We infer that the enhancement of the East Asian winter monsoon (EAWM) during the middle Eocene was closely related to long-term global cooling, while the intensified East Asian summer monsoon (EASM) was primarily caused by the northward drift of the Indian Subcontinent and the uplift of the Tibetan Plateau. • Paleogene palynoflora were systematically studied in southern China. • Paleogene palynoflora of southern China reveals two completely different environmental patterns. • A major environmental shift roughly occurred around the middle Eocene in southern China. • Quantitative estimates show the middle Eocene climate in southern China typical of the modern East Asia Monsoon. [ABSTRACT FROM AUTHOR]

Observational and Mendelian randomization (MR) studies have established links between dyslipidemia and select cancer susceptibilities. However, there is a lack of comprehensive exploration of causal relationships spanning diverse cancer types. Here, we conducted a two-sample MR analysis to elucidate the causative connections between 9 blood lipid metabolic profiles (namely, adiponectin, leptin, lipoprotein A, apolipoprotein A1, apolipoprotein B, cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol) and 21 site-specific cancer risks. Our findings reveal genetically predicted adiponectin levels to be associated with a reduced ovarian cancer risk, while genetically determined leptin increases bladder cancer risk but decreases prostate cancer risk. Lipoprotein A elevates risk of prostate cancer while diminishing risk of endometrial cancer, while apolipoprotein A1 heightens risks of breast and cervical cancers. Furthermore, elevated levels of cholesterol are positively correlated with kidney cancer, and triglycerides demonstrate a positive association with non-melanoma skin cancer but a negative association with breast cancer. Protective effects of genetically predicted LDL-cholesterol on endometrial cancer and adverse effects of HDL-cholesterol on breast cancer are also observed. Our study conclusively establishes that blood lipid metabolic profiles exert causal effects on cancer susceptibility, providing more robust evidence for cancer prevention and prompting contemplation regarding the future health of the human populace. [ABSTRACT FROM AUTHOR]

Objective: To conduct a systematic review and meta-analysis to investigate the clinical efficacy of acupuncture combined with active exercise training in improving pain and function of knee osteoarthritis (KOA) individuals. Data sources: PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Data, Technology Periodical Database and China Biology Medicine were searched from their inceptions to April 5, 2023. Review methods: We analyzed trials of acupuncture combined with active exercise training for KOA. The included studies were of high quality (Jadad ≥ 4) and RCTs. Study selection, data extraction, risk of bias and quality assessment were independently performed by two reviewers. We performed systematic analyses based on different outcome measures, including total efficiency rate, visual analogue scale (VAS), the Western Ontario and Mcmaster Universities Osteoarthritis Index (WOMAC), the Lysholm Knee Scale (LKS) and range of motion (ROM). We used Review Manager 5.3 and Stata/MP 14.0 to analyze the data. And it was verified by trial sequence analysis (TSA). If I2 > 50% and p < 0.05, we performed sensitivity analysis and subgroup analysis to find the source of heterogeneity. Publication bias was studied by funnel plot and Egger's test was used to verify it. Results: Full 11 high-quality studies (Jadad ≥ 4) including 774 KOA individuals were included in this review for meta-analysis. The results showed that acupuncture combined with active exercise training (combined group) was superior to the acupuncture group in improving the total effective rate [RR = 1.13, 95%CI (1.05, 1.22), I2 = 0%, P = 0.70], reducing the pain level (VAS) [MD = − 0.74, 95%CI (− 1.04, − 0.43), I2 = 68%, P < 0.05], improving knee joint function (WOMAC) [MD = − 6.97, 95%CI (− 10.74, − 3.19), I2 = 76%, P < 0.05] and improving joint range of motion (ROM) [MD = 6.25, 95%CI (2.37, 10.04), I2 = 0%, P = 0.71]. Similarly, the combined group showed significant improvements in the total effective rate [RR = 1.31, 95% CI (1.18, 1.47), I2 = 48%, P = 0.10], pain (VAS) [MD = 1.42, 95% CI (− 1.85, − 1.00), I2 = 65%, P = 0.02] and knee function (WOMAC) [MD = 7.05, 95% CI (− 11.43, − 2.66), I2 = 86%, P < 0.05] compared with the non-acupuncture group. Conclusion: The combined effect of all studies showed significant benefits of acupuncture combined with active exercise training in improving the total effective rate, reducing pain, promoting recovery of knee function and expanding range of motion. However, some evaluation indicators are highly subjective and need to be further confirmed by more objective and evidence-based high-quality RCTs in future. Systematic Review Registration: [PROSPERO], identifier [No. CRD42023425823]. [ABSTRACT FROM AUTHOR]

[Display omitted] • LiTi 2 (PO 4) 3 as a precursor is synthesized by the solvothermal method and calcinated in N 2. • LiTi 2 (PO 4) 3 –7h exhibits excellent electrochemical performance. • LiTi 2 (PO 4) 3 –7h exhibits the initial discharge capacity of 123.3 mAh·g−1 at 10C. Nanoparticle LiTi 2 (PO 4) 3 was prepared by solvothermal and calcination methods. LiTi 2 (PO 4) 3 -xh(x = 5, 7, 9, 13) was successfully synthesized under different calcination times in nitrogen atmosphere, and LiTi 2 (PO 4) 3 –7h showed excellent rate and electrochemical performance. It delivered discharge capacities of 141.2, 119.9, 109.8, 98.2, 87.3, and 76.7 mAh·g−1 at rates of 0.5, 1, 2, 5, 10, and 20C, respectively. In particular, its initial discharge capacity can reach 123.3 mAh·g−1 at the high rate of 10C. Hence, these superior properties demonstrate that LiTi 2 (PO 4) 3 –7h has great application advantages as a cathode for lithium-ion batteries. [ABSTRACT FROM AUTHOR]

The sedimentary strata from the Late Cretaceous to Early Eocene in the Himalayan foothills offer detailed insights into land collision processes. Unfortunately, a comprehensive dating study on these strata has been lacking, limiting our understanding of the collision and splicing history of the Indian and Lhasa plates. To address this question, we conducted a paleomagnetic study on the Late Cretaceous to Early Eocene succession in the Tulsipur area, western Nepal. The paleomagnetic data obtained from a 357 m thick succession were used to establish a new magnetostratigraphic framework for this region. The observed magnetic polarity sequence contains six normal and six reversed polarity zones, spanning the age range of 68–54 Ma (Maastrichtian to Early Eocene). In addition, two major and two stable sediment accumulation rates (SARs) were identified which were likely controlled by tectonics. The rifting and subsidence events caused by continuous northward movement of the Indian plate might have modulated the shifting of distal offshore to tidal flat settings in this region. We document fifteen (Unit I) and seven (Unit II) transgressive-regressive cycles, indicative of passive margin instability influenced by near-field effects of the India-Asian convergence. This new magnetostratigraphic result is expected to serve as a basic age framework in reconstructing the Late Mesozoic and Early Cenozoic tectonic evolution. Furthermore, it will also facilitate reliable cross-regional correlation between lithostratigraphic units across passive margins in the southern Himalaya and similar strata in the Tethyan Himalaya and active continental margins of the southern Tibetan Plateau. [Display omitted] • Magnetostratigraphy dates a section ranging from ∼68 to 54 Ma. • Sediment accumulation rates changes, indicating shifts from distal offshore to tidal flat settings. • Rifting and subsidence events released passive margins instability in the southern foothills of Himalayas. [ABSTRACT FROM AUTHOR]

The distribution pattern of arid–humid climate in the modern northwest–southeast confrontation in Asia evolved from the zonal distribution pattern of the Paleogene. However, this evolutionary process remains poorly constrained by geological evidence. In this paper, we analyze the characteristics of sporopollen assemblages recorded in Late Eocene strata of the Jianchuan Basin in southwest China. We show that vegetation patterns exhibited a remarkable shift from tropical–subtropical sparse forest to subtropical–temperate mixed broad-leaved–coniferous forest at ∼40.6 Ma; this shift is further indicated by the rapid decrease in drought-tolerant plants, mostly Ephedra and Chenopodiaceae, evidence that the previous hot–dry climate was replaced by a warm–humid climate at this time. This evidence suggests that the Asian monsoon began to affect the study area at ∼40.6 Ma. We then comprehensively integrated sporopollen results from several basins across East Asia, revealing that the frontal edge of the humid monsoon climate moved intermittently to the northwest after the Late Eocene, and may have advanced to the Lunpola–Lanzhou line by the early Late Oligocene, this being similar to the position of the leading edge of the modern monsoon. Moreover, the frontal edge of the humid monsoon climate may have extended as far as the Qaidam Basin during the Middle Miocene, but then gradually retreated to the position of the modern monsoon front. The uplift of the Tibetan Plateau and global climate change may have played dominant roles in this evolution. • A Late Eocene sporopollen record was obtained from the subtropical Yunnan region. • The Asian monsoon extended from tropical to subtropical regions around 40.6 Ma. • The Asian monsoon reached the modern monsoon front in the early Late Oligocene. • The Asian monsoon advanced on one occasion to the Qaidam Basin in the Mid-Miocene. [ABSTRACT FROM AUTHOR]

Remdesivir (RDV) is the first drug approved by the FDA for clinical treatment of hospitalized patients infected with COVID-19 because it has been shown to have good antiviral activity against a variety of viruses, including Arenaviridae and Coronaviridae viral families. However, it has been reported that its clinical treatment leads to the symptoms of sick sinus syndrome such as sinus bradycardia, conduction block, and sinus arrest, but the electrophysiological mechanism of its specific cardiac adverse events is still unclear. We report complementary, experimental, studies of its electrophysiological effects. In wireless cardiac telemetry experiments in vivo and electrocardiographic studies in ex vivo cardiac preparations, RDV significantly caused sinus bradycardia, sinus atrial block, and prolongation of the QT interval in guinea pigs. Dose-dependent effects of RDV on the electrical activities of sinoatrial node (SA node) preparations of guinea pigs were characterised by multielectrode, optical RH237 voltage mapping. These revealed reversibly reduced sinoatrial conduction time (SACT), increased AP durations (APDs), and decreased the pacemaking rate of the SA node. Patch-clamp experiments showed that RDV significantly inhibited the I f current of HCN4 channels, resulting in a significant decrease in the spontaneous firing rate of SA node cells, which may underlie the development of sick sinus node syndrome. In addition, RDV significantly inhibits I Kr currents in hERG channels, leading to prolongation of the QT interval and playing a role in bradycardia. Therefore, these findings provide insights into the understanding the bradycardia effect of RDV, which may be used as basic theoretical guidance for the intervention of its adverse events, and prompt safety investigations of RDV's cardiac safety in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Yue, Xie and Zhang.)

Ageing is an inevitable process that affects various tissues and organs of the human body, leading to a series of physiological and pathological changes. Mechanisms such as telomere depletion, stem cell depletion, macrophage dysfunction, and cellular senescence gradually manifest in the body, significantly increasing the incidence of diseases in elderly individuals. These mechanisms interact with each other, profoundly impacting the quality of life of older adults. As the ageing population continues to grow, the burden on the public health system is expected to intensify. Globally, the prevalence of musculoskeletal system diseases in elderly individuals is increasing, resulting in reduced limb mobility and prolonged suffering. This review aims to elucidate the mechanisms of ageing and their interplay while exploring their impact on diseases such as osteoarthritis, osteoporosis, and sarcopenia. By delving into the mechanisms of ageing, further research can be conducted to prevent and mitigate its effects, with the ultimate goal of alleviating the suffering of elderly patients in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cai, Han, Cheng, Li, Wang, Chen, Liu, Xie, Lin, Zhou, Wang, Zhou and Jin.)

Despite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method and the choice of genomic regions 1-3 . Here we address these issues by analysing the genomes of 363 bird species 4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a marked degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous-Palaeogene boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that are a challenge to model due to either extreme DNA composition, variable substitution rates, incomplete lineage sorting or complex evolutionary events such as ancient hybridization. Assessment of the effects of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates and relative brain size following the Cretaceous-Palaeogene extinction event, supporting the hypothesis that emerging ecological opportunities catalysed the diversification of modern birds. The resulting phylogenetic estimate offers fresh insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Genome-wide circulating cell-free DNA (ccfDNA) fragmentation for cancer detection has been rarely evaluated using blood samples collected before cancer diagnosis. To evaluate ccfDNA fragmentation for detecting early hepatocellular carcinoma (HCC), we first modeled and tested using hospitalized HCC patients and then evaluated in a population-based study. A total of 427 samples were analyzed, including 270 samples collected prior to HCC diagnosis from a population-based study. Our model distinguished hospital HCC patients from controls excellently (area under curve 0.999). A high ccfDNA fragmentation score was highly associated with an advanced tumor stage and a shorter survival. In evaluation, the model showed increasing sensitivities in detecting HCC using 'pre-samples' collected ≥4 years (8.3%), 3-4 years (20.0%), 2-3 years (31.0%), 1-2 years (35.0%), and 0-1 year (36.4%) before diagnosis. These findings suggested ccfDNA fragmentation is sensitive in clinical HCC detection and might be helpful in screening early HCC., Competing Interests: Z.Z. receives patent royalty from ArcherDX; is a scientific advisor for and holds equity in GenEditBio; these interests are reviewed and regulated by institutional Outside Practice and Outside Work policies annually. Z.Z. and S.L. have filed patent based on the WGS method. The other authors declare no competing interests., (© 2024 The Author(s).)

Background: Dickkopf-1 (DKK1) exhibits abnormal expression in various cancers and correlates with poor prognosis. This study investigates DKK1's prognostic relevance in head and neck squamous cell carcinoma (HNSC)., Methods: We conducted a comprehensive search across literature and sequencing databases to gather eligible studies and HNSC datasets. We calculated pooled standardized mean differences (SMD) and 95% confidence intervals (CI) for clinical characteristics, as well as hazard ratios (HR) with 95% CIs for overall survival (OS) and progression-free/disease-free survival (PFS/DFS). Sensitivity analysis gauged result stability, and Egger's test assessed publication bias., Results: Pooled results indicated that HNSC patients with higher T-stage exhibited elevated DKK1 expression levels, and this elevated expression was associated with shorter OS and PFS/DFS. While sensitivity analysis identified some studies significantly affecting pooled results, most were unaffected, and no publication bias was detected., Conclusion: DKK1 holds promise as a potential biomarker for predicting poor prognosis in HNSC patients, but further research is needed for confirmation.

Objective: To investigate the effects of vestibular rehabilitation training (VRT) combined with anti-vertigo drugs on vertigo and balance function in patients with vestibular neuronitis (VN)., Data Sources: PubMed, EMBASE, The Cochrane Library, Web of Science, CNKI, Wan Fang Data, VIP, and CBM were searched until July 13, 2023., Participants: Patients with vestibular neuronitis participated in the study., Results: Twenty one studies including 1,415 patients were included in this review for meta-analysis. According to the Physiotherapy Evidence Database (PEDro) quality assessment, four studies received high quality (≥seven scores) and 17 studies received moderate quality (six scores). The meta-analysis showed that VRT combined with anti-vertigo drugs significantly reduced the Dizziness Handicap Inventory (DHI) score, the Vestibular Disorders Activities of Daily Living Scale (VADL) score and the Canal Paresis (CP) score, and improved the overall efficiency and the Berg Balance Scale (BBS) score, promoting vestibular evoked myogenic potentials (VEMPs) returned to normal in VN compared to simple anti-vertigo drugs or VRT alone., Conclusion: The results of this meta-analysis demonstrate the efficacy and safety of VRT combined with anti-vertigo drugs in patients with VN. Combined therapy can alleviate vestibular dysfunction such as vertigo and vomiting in patients, improve daily activity ability and balance ability, in addition to VRT has fewer adverse reactions, so it is extremely safe. However, there are shortcomings such as lack of long-term follow-up and different frequency and duration of treatment. Therefore, future randomized controlled trials (RCTs) with larger sample sizes and longer-term observations are needed to verify the effectiveness of VRT in combination with anti-vertigo drugs for VN. Systematic Review Registration : https://www.crd.york.ac.uk/prospero/., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Liu, Xie and Jin.)

T-wave alternans (TWA) has been used for predicting the risk of malignant cardiac arrhythmias and sudden cardiac death (SCD) in multiple clinical settings; however, possible mechanism(s) underlying the spontaneous transition from cellular alternans reflected by TWA to arrhythmias in impaired repolarization remains unclear. The healthy guinea pig ventricular myocytes under E-4031 blocking I Kr (0.1 μM, N = 12; 0.3 μM, N = 10; 1 μM, N = 10) were evaluated using whole-cell patch-clamp. The electrophysiological properties of isolated perfused guinea pig hearts under E-4031 (0.1 μM, N = 5; 0.3 μM, N = 5; 1 μM, N = 5) were evaluated using dual- optical mapping. The amplitude/threshold/restitution curves of action potential duration (APD) alternans and potential mechanism(s) underlying the spontaneous transition of cellular alternans to ventricular fibrillation (VF) were examined. There were longer APD 80 and increased amplitude and threshold of APD alternans in E-4031 group compared with baseline group, which was reflected by more pronounced arrhythmogenesis at the tissue level, and were associated with steep restitution curves of the APD and the conduction velocity (CV). Conduction of AP alternans augmented tissue's functional spatiotemporal heterogeneity of regional AP/Ca alternans, as well as the AP/Ca dispersion, leading to localized uni-directional conduction block that spontaneous facilitated the formation of reentrant excitation waves without the need for additional premature stimulus. Our results provide a possible mechanism for the spontaneous transition from cardiac electrical alternans in cellular action potentials and intercellular conduction without the involvement of premature excitations, and explain the increased susceptibility to ventricular arrhythmias in impaired repolarization. In this study, we implemented voltage-clamp and dual-optical mapping approaches to investigate the underlying mechanism(s) for the arrhythmogenesis of cardiac alternans in the guinea pig heart at cellular and tissue levels. Our results demonstrated a spontaneous development of reentry from cellular alternans, arising from a combined actions of restitution properties of action potential duration, conduction velocity of excitation wave and interplay between alternants of action potential and the intracellular Ca handling. We believe this study provides new insights into underlying the mechanism, by which cellular cardiac alternans spontaneously evolves into cardiac arrhythmias., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Upper limb motor dysfunction after stroke is an important factor affecting patients' motor function and daily life. Acupuncture and repetitive transcranial magnetic stimulation are effective methods for stroke rehabilitation. However, a systematic and comprehensive overview of the combined efficacy of the two is lacking., Objective: Through a systematic review and meta-analysis of randomized controlled trials, this study aimed to assess the effectiveness of acupuncture combined with repetitive transcranial magnetic stimulation on upper extremity motor function in post-stroke patients., Methods: The relevant randomized controlled trials on acupuncture combined with repetitive transcranial magnetic stimulation in the treatment of upper limb motor disorders after stroke were searched in PubMed, Embase, Cochrane Library, Web of Science CNKI, VIP, Wanfang, and CBM databases. After screening clinical trials that met the inclusion criteria, data extraction was conducted independently by two investigators. Meta-analysis was performed using RevMan 5.4 software., Results: After the screening, 18 articles were included, with a total of 1083 subjects. The results of meta-analysis showed that combination therapy could effectively improve the patients' upper limb motor function (MD = 7.77, 95%CI [6.32, 9.22], P < 0.05), ability of daily living (MD = 8.53, 95%CI [6.28, 10.79], P < 0.05), and hemiplegic shoulder pain (MD = - 1.72, 95%CI [- 2.26, - 1.18], P < 0.05). Meanwhile, for neurophysiological indexes, combined treatment could significantly shorten the latency of motor evoked potential and central motor conduction time (MD = - 1.42, 95%CI [- 2.14, - 0.71], P < 0.05); (MD = - 0.47, 95%CI [- 0.66, - 0.29], P < 0.05), and also could increase the amplitude of motor evoked potential (SMD = 0.71, 95%CI [0.28, 1.14], P < 0.05)., Conclusion: According to the results of the meta-analysis, we can conclude that acupuncture combined with repeated transcranial magnetic stimulation can significantly improve the upper limb motor function and daily living ability of stroke patients.