Pharmacological inhibition of Kir4.1 evokes rapid-onset antidepressant responses.

Major depressive disorder, a prevalent and severe psychiatric condition, necessitates development of new and fast-acting antidepressants. Genetic suppression of astrocytic inwardly rectifying potassium channel 4.1 (Kir4.1) in the lateral habenula ameliorates depression-like phenotypes in mice. However, Kir4.1 remains an elusive drug target for depression. Here, we discovered a series of Kir4.1 inhibitors through high-throughput screening. Lys05, the most potent one thus far, effectively suppressed native Kir4.1 channels while displaying high selectivity against established targets for rapid-onset antidepressants. Cryogenic-electron microscopy structures combined with electrophysiological characterizations revealed Lys05 directly binds in the central cavity of Kir4.1. Notably, a single dose of Lys05 reversed the Kir4.1-driven depression-like phenotype and exerted rapid-onset (as early as 1 hour) antidepressant actions in multiple canonical depression rodent models with efficacy comparable to that of (S)-ketamine. Overall, we provided a proof of concept that Kir4.1 is a promising target for rapid-onset antidepressant effects.

MGF6mARice: prediction of DNA N6-methyladenine sites in rice by exploiting molecular graph feature and residual block.

DNA N6-methyladenine (6mA) is produced by the N6 position of the adenine being methylated, which occurs at the molecular level, and is involved in numerous vital biological processes in the rice genome. Given the shortcomings of biological experiments, researchers have developed many computational methods to predict 6mA sites and achieved good performance. However, the existing methods do not consider the occurrence mechanism of 6mA to extract features from the molecular structure. In this paper, a novel deep learning method is proposed by devising DNA molecular graph feature and residual block structure for 6mA sites prediction in rice, named MGF6mARice. Firstly, the DNA sequence is changed into a simplified molecular input line entry system (SMILES) format, which reflects chemical molecular structure. Secondly, for the molecular structure data, we construct the DNA molecular graph feature based on the principle of graph convolutional network. Then, the residual block is designed to extract higher level, distinguishable features from molecular graph features. Finally, the prediction module is used to obtain the result of whether it is a 6mA site. By means of 10-fold cross-validation, MGF6mARice outperforms the state-of-the-art approaches. Multiple experiments have shown that the molecular graph feature and residual block can promote the performance of MGF6mARice in 6mA prediction. To the best of our knowledge, it is the first time to derive a feature of DNA sequence by considering the chemical molecular structure. We hope that MGF6mARice will be helpful for researchers to analyze 6mA sites in rice.

ggmsa: a visual exploration tool for multiple sequence alignment and associated data.

The identification of the conserved and variable regions in the multiple sequence alignment (MSA) is critical to accelerating the process of understanding the function of genes. MSA visualizations allow us to transform sequence features into understandable visual representations. As the sequence-structure-function relationship gains increasing attention in molecular biology studies, the simple display of nucleotide or protein sequence alignment is not satisfied. A more scalable visualization is required to broaden the scope of sequence investigation. Here we present ggmsa, an R package for mining comprehensive sequence features and integrating the associated data of MSA by a variety of display methods. To uncover sequence conservation patterns, variations and recombination at the site level, sequence bundles, sequence logos, stacked sequence alignment and comparative plots are implemented. ggmsa supports integrating the correlation of MSA sequences and their phenotypes, as well as other traits such as ancestral sequences, molecular structures, molecular functions and expression levels. We also design a new visualization method for genome alignments in multiple alignment format to explore the pattern of within and between species variation. Combining these visual representations with prime knowledge, ggmsa assists researchers in discovering MSA and making decisions. The ggmsa package is open-source software released under the Artistic-2.0 license, and it is freely available on Bioconductor (https://bioconductor.org/packages/ggmsa) and Github (https://github.com/YuLab-SMU/ggmsa).

Revealing of long-range soliton interaction induced time and phase dynamics in a mode-locked fiber laser.

By means of the dispersive temporal interferometry technique, we carried out a real-time observation of the time separation and relative phase evolutions of two pulses toward harmonic mode-locking. During the separation stage of the buildup process, the time separation increases, while the relative phase decreases synchronously, and the largest change rates are 0.247 fs/r and -0.017 rad/r, respectively. Meanwhile, the two rates show a linear relation with the former 17.4 times larger than the latter. Moreover, a residual phase change rate of -3.89 × 10-4 rad/r is observed in a steady non-uniform dual-soliton state, while such phase change is absent in a uniform four-soliton state. This study unveils the soliton interaction dynamics in lasers, which not only help to reduce timing jitter in multi-soliton mode-locking, but also bring insight to a temporal tweezing of femtosecond pulse.

Real-time revealing of Cherenkov radiation evolution in optical fibers.

The generation of Cherenkov radiation (CR) is determined by the phase-matching condition, but the experimental observation on the phase change of its transient process is still incomplete. In this paper, we use the dispersive temporal interferometer (DTI) technique to real-time reveal the buildup and evolution of CR. Experiments show that when the pump power varies, the phase-matching conditions also change, which is mainly affected by the nonlinear phase shift caused by the Kerr effect. Further simulation results propose that both pulse power and pre-chirp management have a significant impact on phase-matching. The CR wavelength can be shortened and the generation position can be moved forward by adding a suitable positive chirp or increasing the incident peak power. Our work directly reveals the evolution of CR in optical fibers and provides a method for optimizing it.

The nonneuronal cholinergic system in the colon: A comprehensive review.

Acetylcholine (ACh) is found not only in cholinergic nerve termini but also in the nonneuronal cholinergic system (NNCS). ACh is released from cholinergic nerves by vesicular ACh transporter (VAChT), but ACh release from the NNCS is mediated by organic cation transporter (OCT). Recent studies have suggested that components of the NNCS are located in intestinal epithelial cells (IECs), crypt-villus organoids, immune cells, intestinal stem cells (ISCs), and vascular endothelial cells (VECs). When ACh enters the interstitial space, its self-modulation or effects on adjacent tissues are part of the range of its biological functions. This review focuses on the current understanding of the mechanisms of ACh synthesis and release in the NNCS. Furthermore, studies on ACh functions in colonic disorders suggest that ACh from the NNCS contributes to immune regulation, IEC and VEC repair, ISC differentiation, colonic movement, and colonic tumor development. As indicated by the features of some colonic disorders, ACh and the NNCS have positive and negative effects on these disorders. Furthermore, the NNCS is located in multiple colonic organs, and the specific effects and cross-talk involving ACh from the NNCS in different colonic tissues are explored.

A short period of early life oxytocin treatment rescues social behavior dysfunction via suppression of hippocampal hyperactivity in male mice.

Early sensory experiences interact with genes to shape precise neural circuits during development. This process is vital for proper brain function in adulthood. Neurological dysfunctions caused by environmental alterations and/or genetic mutation may share the same molecular or cellular mechanisms. Here, we show that early life bilateral whisker trimming (BWT) subsequently affects social discrimination in adult male mice. Enhanced activation of the hippocampal dorsal CA3 (dCA3) in BWT mice was observed during social preference tests. Optogenetic activation of dCA3 in naive mice impaired social discrimination, whereas chemogenetic silencing of dCA3 rescued social discrimination deficit in BWT mice. Hippocampal oxytocin (OXT) is reduced after whisker trimming. Neonatal intraventricular compensation of OXT relieved dCA3 over-activation and prevented social dysfunction. Neonatal knockdown of OXT receptor in dCA3 mimics the effects of BWT, and cannot be rescued by OXT treatment. Social behavior deficits in a fragile X syndrome mouse model (Fmr1 KO mice) could also be recovered by early life OXT treatment, through negating dCA3 over-activation. Here, a possible avenue to prevent social dysfunction is uncovered.

The ATR-WEE1 kinase module inhibits the MAC complex to regulate replication stress response.

DNA damage response is a fundamental mechanism to maintain genome stability. The ATR-WEE1 kinase module plays a central role in response to replication stress. Although the ATR-WEE1 pathway has been well studied in yeasts and animals, how ATR-WEE1 functions in plants remains unclear. Through a genetic screen for suppressors of the Arabidopsis atr mutant, we found that loss of function of PRL1, a core subunit of the evolutionarily conserved MAC complex involved in alternative splicing, suppresses the hypersensitivity of atr and wee1 to replication stress. Biochemical studies revealed that WEE1 directly interacts with and phosphorylates PRL1 at Serine 145, which promotes PRL1 ubiquitination and subsequent degradation. In line with the genetic and biochemical data, replication stress induces intron retention of cell cycle genes including CYCD1;1 and CYCD3;1, which is abolished in wee1 but restored in wee1 prl1. Remarkably, co-expressing the coding sequences of CYCD1;1 and CYCD3;1 partially restores the root length and HU response in wee1 prl1. These data suggested that the ATR-WEE1 module inhibits the MAC complex to regulate replication stress responses. Our study discovered PRL1 or the MAC complex as a key downstream regulator of the ATR-WEE1 module and revealed a novel cell cycle control mechanism.

Evaluation of the accuracy of cone-beam computed tomography image segmentation of isolated tooth roots based on the dynamic threshold method.

OBJECTIVE: Accurate quantification of the root surface area (RSA) plays a decisive role in the advancement of periodontal, orthodontic, and restorative treatment modalities. In this study, we aimed to develop a dynamic threshold-based computer-aided system for segmentation and calculation of the RSA of isolated teeth on cone-beam computed tomography (CBCT) and to assess the accuracy of the measured data. METHOD: We selected 24 teeth to be extracted, including single-rooted and multi-rooted teeth, from 22 patients who required tooth extraction. In the experimental group, we scanned 24 isolated teeth using CBCT with a voxel size of 0.3 mm. We designed a computer-aided system based on a personalized dynamic threshold algorithm to automatically segment the roots of 24 isolated teeth in CBCT images and calculate the RSA. In the control group, we employed digital intraoral scanner devices to perform optical scanning on 24 isolated teeth and subsequently manually segmented the roots using 3-matic software to calculate the RSA. We used the paired t-test (P < 0.05) and Bland-Altman plots to analyze the consistency of the two measurement methods. RESULTS: The results of the paired t-test showed that there was no significant difference in the RSAs obtained using the dynamic threshold method and the optical scanning image reconstruction (t = 1.005, P = 0.325 > 0.05). As per the Bland-Altman plot, the results were evenly distributed within the region of ± 1.96 standard deviations of the mean, with no increasing or decreasing trends and good consistency. CONCLUSION: In this study, we designed a computer-aided root segmentation system based on a personalized dynamic threshold algorithm to automatically segment the roots of isolated teeth in CBCT images with a voxel size of 0.3 mm. We found that the RSA calculated using this approach was highly accurate, and a voxel of 0.3 mm in size could accurately display the surface area data in CBCT images. Overall, our findings in this study provide a foundation for future work on accurate automatic segmentation of tooth roots in full-mouth CBCT images and the computation of RSA.

Atroposelective Synthesis of C-N Vinylindole Atropisomers by Palladium-Catalyzed Asymmetric Hydroarylation of 1-Alkynylindoles.

Transition-metal-catalyzed hydroarylation of unsymmetrical internal alkynes remains challenging because of the difficulty in controlling regioselectivity and stereoselectivity. Moreover, the enantioselective hydroarylation of alkynes using organoboron reagents has not been reported. Herein, we report for the first time that palladium compounds can catalyze the hydroarylation of 1-alkynylindoles with organoborons for the synthesis of chiral C-N atropisomers. A series of rarely reported vinylindole atropisomers was synthesized with excellent regio-, stereo- (Z-selectivity), and enantioselectivity under mild reaction conditions. The ready availability of organoborons and alkynes and the simplicity, high stereoselectivity, and good functional group tolerance of this catalytic system make it highly attractive.

Enantioselective Synthesis of N-N Atropisomers by Palladium-Catalyzed C-H Functionalization of Pyrroles.

The catalytic asymmetric construction of N-N atropisomeric biaryls remains a formidable challenge. Studies of them lag far behind studies of the more classical carbon-carbon biaryl atropisomers, hampering meaningful development. Herein, the first palladium-catalyzed enantioselective C-H activation of pyrroles for the synthesis of N-N atropisomers is presented. Structurally diverse indole-pyrrole atropisomers possessing a chiral N-N axis were produced with good yields and high enantioselectivities by alkenylation, alkynylation, allylation, or arylation reactions. Furthermore, the kinetic resolution of trisubstituted N-N heterobiaryls with more sterically demanding substituents was also achieved. Importantly, this versatile C-H functionalization strategy enables iterative functionalization of pyrroles with exquisite selectivity, expediting the formation of valuable, complex, N-N atropisomers.

Resveratrol-induced Sirt1 phosphorylation by LKB1 mediates mitochondrial metabolism.

The NAD+-dependent deacetylase Sirt1 has been implicated in the prevention of many age-related diseases, including cancer, type 2 diabetes, and cardiovascular disease. Resveratrol, a plant polyphenol, exhibits antiaging, antitumor, and vascular protection effects by activating Sirt1. However, the molecular mechanism of Sirt1 activation as induced by resveratrol remains unclear. By knockdown/rescue experiments, fluorometric Sirt1 activity assay, immunoprecipitation, and pull-down assays, we identify here that the tumor suppressor LKB1 (liver kinase B1) as a direct activator of Sirt1 elicited by resveratrol. Resveratrol promotes the binding between LKB1 and Sirt1, which we first reported, and this binding leads to LKB1-mediated phosphorylation of Sirt1 at three different serine residues in the C terminus of Sirt1. Mechanistically, LKB1-mediated phosphorylation increases intramolecular interactions in Sirt1, such as the binding of the C terminus to the deacetylase core domain, thereby eliminating DBC1 (Deleted in Breast Cancer 1, Sirt1 endogenous inhibitor) inhibition and promoting Sirt1-substrate interaction. Functionally, LKB1-dependent Sirt1 activation increases mitochondrial biogenesis and respiration through deacetylation and activation of the transcriptional coactivator PGC-1α. These results identify Sirt1 as a context-dependent target of LKB1 and suggest that a resveratrol-stimulated LKB1-Sirt1 pathway plays a vital role in mitochondrial metabolism, a key physiological process that contributes to numerous age-related diseases.

Epilepsy phenotype and response to KCNQ openers in mice harboring the Kcnq2 R207W voltage-sensor mutation.

KCNQ2-encoded Kv7.2 subunits play a critical role in balancing neuronal excitability. Mutations in KCNQ2 are responsible for highly-heterogenous epileptic and neurodevelopmental phenotypes ranging from self-limited familial neonatal epilepsy (SeLFNE) to severe developmental and epileptic encephalopathy (DEE). Pathogenic KCNQ2 variants cluster at the voltage sensor domain (VSD), the pore domain, and the C-terminal tail. Although several knock-in mice harboring Kcnq2 pore variants have been developed, no mouse line carrying Kcnq2 voltage-sensor mutations has been described. KCNQ2-R207W is an epilepsy-causing mutation located in the VSD, mainly affecting voltage-dependent channel gating. To study the physiological consequence of Kcnq2 VSD dysfunction, we generated a Kcnq2-R207W mouse line and analyzed the pathological and pharmacological phenotypes of mutant mice. As a result, both homozygous (Kcnq2RW/RW) and heterozygous (Kcnq2RW/+) mice were viable. While Kcnq2RW/RW mice displayed a short lifespan, growth retardation, and spontaneous seizures, Kcnq2RW/+ mice survived and developed normally, although only a fraction (9/64; 14%) of them showed behavioral- and ECoG-confirmed spontaneous seizures. Kcnq2RW/+ mice displayed increased susceptibility to evoked seizures, which was dramatically ameliorated by treatment with the novel KCNQ opener pynegabine (HN37). Our results show that the Kcnq2-R207W mouse line, the first harboring a Kcnq2 voltage-sensor mutation, exhibits a unique epileptic phenotype with both spontaneous seizures and increased susceptibility to evoked seizures. In Kcnq2-R207W mice, the potent KCNQ opener HN37, currently in clinical phase I, shows strong anticonvulsant activity, suggesting it may represent a valuable option for the severe phenotypes of KCNQ2-related epilepsy.

ggtreeExtra: Compact Visualization of Richly Annotated Phylogenetic Data.

We present the ggtreeExtra package for visualizing heterogeneous data with a phylogenetic tree in a circular or rectangular layout (https://www.bioconductor.org/packages/ggtreeExtra). The package supports more data types and visualization methods than other tools. It supports using the grammar of graphics syntax to present data on a tree with richly annotated layers and allows evolutionary statistics inferred by commonly used software to be integrated and visualized with external data. GgtreeExtra is a universal tool for tree data visualization. It extends the applications of the phylogenetic tree in different disciplines by making more domain-specific data to be available to visualize and interpret in the evolutionary context.

Towards optimal conversion efficiency of Brillouin random fiber lasers in a half-open linear cavity.

We proposed and demonstrated an unprecedented high-efficiency Brillouin random fiber laser (BRFL) by fiber length optimization in a half-open linear cavity. In terms of the trade-off between Brillouin gain saturation and weak distributed Rayleigh feedback strength, optimal laser efficiency associated to proper fiber length in a BRFL was theoretically predicted. As a proof-of-concept, a unidirectional-pumped BRFL with a half-open linear cavity was experimentally conducted, in which a fiber Bragg grating at one end of gain fiber served as a high-reflection mirror while Rayleigh scattering enabled distributed feedback for random lasing resonance. Results show that the optimal fiber length of ∼3.4 km in the BRFL offers sufficient Rayleigh scattered random feedback whilst alleviating the Brillouin gain saturation to a large extent. Consequently, an optimal laser efficiency of 77.0% in the BRFL was experimentally demonstrated, which reaches the state-of-the-art high record. Laser characteristics, including the linewidth, statistics and frequency jitter were also systematically investigated. It is believed that such efficient BRFL could provide a promising platform for inspiring new explorations of laser physics as well as potentials in long-haul coherent communication and fiber-optic sensing.

Real-time observation of phase transition of bifurcation evolution in mode-locked lasers.

By using the dispersive temporal holography technology, we observe the real-time dynamics of period-doubling bifurcation evolution in an ultrafast fiber laser. The pulse properties including the phase, polarization state, chirp, pulse width, and pulse energy are fully bifurcated, which embody the bifurcation induced "phase transition." There are two types of bifurcation in the laser buildup: one to many bifurcation towards the chaos and the multiple bifurcated pulses back to the stationary state along the reversed trajectory. Both of them can be explained by the rule of the same phase transition. We conclude and illustrate the differences and connections to another common pulsation, the Hopf bifurcation. The findings can promote an understanding of the bifurcations in ultrafast lasers, and are beneficial for an improvement of laser stability.

Impact of posttransplant cyclophosphamide on the outcome of patients undergoing unrelated single-unit umbilical cord blood transplantation for pediatric acute leukemia.

BACKGROUND: Umbilical cord blood transplantation (UCBT) from unrelated donors is one of the successful treatments for acute leukemia in childhood. The most frequent side effect of UCBT is peri-engraftment syndrome (PES), which is directly associated with the greater prevalence of acute and chronic graft-versus-host-disease (aGvHD and cGvHD). In haploidentical stem cell transplantation, posttransplant cyclophosphamide (PTCY) has been demonstrated to be an effective method against GvHD. However, the effects of PTCY as a GvHD prophylactic in UCBT had not been investigated. This study aimed to evaluate the effects of PTCY on the outcomes of UCBT for pediatric acute leukemia. METHODS: This retrospective study included 52 children with acute leukemia who underwent unrelated single-unit UCBT after myeloablative conditioning regimens. The results from the PTCY and non-PTCY groups were compared. RESULTS: The incidence of transplantation-related mortality in non-PTCY and PTCY were 5% and 10% (p = 0.525), respectively. The incidence of relapse in non-PTCY and PTCY were 5% and 23% (p = 0.095), respectively. Second complete remission status (CR2) was an independent risk factor for relapse-free survival (hazard ratio = 9.782, p = 0.001). The odds ratio for sepsis or bacteremia incidence was significantly greater in the PTCY group (9.524, p = 0.017). PTCY group had increased rates of cytomegalovirus activity and fungal infection. The incidence of PES, aGvHD, cGvHD, and hemorrhagic cystitis in the PTCY group was lower than that in the non-PTCY group, although it was not significantly different. Additionally, higher doses of PTCY (29 mg/kg and 40 mg/kg) were associated with lower incidences of aGvHD and severe GvHD (65% and 29%, respectively) than lower doses (93% and 57%, respectively). Engraftment time and graft failure incidence were similar across groups. CONCLUSION: The results support the safety and efficiency of PTCY as part of PES controlling and GvHD prophylaxis in single-unit UCBT for children with acute leukemia. A PTCY dosage of 29 mg/kg to 40 mg/kg appears to be more effective in GvHD prophylaxis for UCBT patients.

SCN8A epileptic encephalopathy mutations display a gain-of-function phenotype and divergent sensitivity to antiepileptic drugs.

De novo missense mutations in SCN8A gene encoding voltage-gated sodium channel NaV1.6 are linked to a severe form of early infantile epileptic encephalopathy named early infantile epileptic encephalopathy type13 (EIEE13). The majority of the patients with EIEE13 does not respond favorably to the antiepileptic drugs (AEDs) in clinic and has a significantly increased risk of death. Although more than 60 EIEE13-associated mutations have been discovered, only few mutations have been functionally analyzed. In this study we investigated the functional influences of mutations N1466T and N1466K, two EIEE13-associated mutations located in the inactivation gate, on sodium channel properties. Sodium currents were recorded from CHO cells expressing the mutant and wide-type (WT) channels using the whole-cell patch-clamp technique. We found that, in comparison with WT channels, both the mutant channels exhibited increased window currents, persistent currents (INaP) and ramp currents, suggesting that N1466T and N1466K were gain-of-function (GoF) mutations. Sodium channel inhibition is one common mechanism of currently available AEDs, in which topiramate (TPM) was effective in controlling seizures of patients carrying either of the two mutations. We found that TPM (100 µM) preferentially inhibited INaP and ramp currents but did not affect transient currents (INaT) mediated by N1466T or N1466K. Among the other 6 sodium channel-inhibiting AEDs tested, phenytoin and carbamazepine displayed greater efficacy than TPM in suppressing both INaP and ramp currents. Functional characterization of mutants N1466T and N1466K is beneficial for understanding the pathogenesis of EIEE13. The divergent effects of sodium channel-inhibiting AEDs on INaP and ramp currents provide insight into the development of therapeutic strategies for the N1466T and N1466K-associated EIEE13.

Effect of postoperative ultrasound-guided internal superior laryngeal nerve block on sore throat after intubation of double-lumen bronchial tube: a randomized controlled double-blind trial.

BACKGROUND: Postoperative sore throat (POST) is one of the main adverse postoperative outcome after tracheal intubation using double-lumen endobronchial tubes (DLTs). The aim of this study was to investigate the effectiveness and safety of ultrasound (US)-guided block of the internal branch of the superior laryngeal nerve (iSLN) for alleviating POST after intubation of DLTs. METHODS: Patients undergoing thoracic surgery between August 2019 and August 2021 were randomized into two groups depending on whether they received US-guided iSLN block immediately after the operation. In the control group, the patients underwent a thoracic surgery under general anesthesia (GA) with DLTs without any special treatment, while the patients in the experimental group received US-guided iSLN block bilaterally with 2 ml of 0.25% ropivacaine on either side immediately after the operation. The primary outcome was the grading of sore throat at three-time points after the operation, i.e., immediate extubation, 2 h after extubation, and 24 h after extubation. Secondary outcomes included the rate of nausea and vomiting, hoarseness, dyspnea, and choking cough after swallowing saliva at 2 h after extubation. RESULTS: The incidence and severity of sore throat were significantly lower in the experimental group than the control group at all time intervals (all P < 0.01). The rate of nausea and vomiting, hoarseness, dyspnea, and choking cough after swallow saliva at 2 h after extubation had no statistical difference (all P > 0.05). CONCLUSIONS: The use of US-guided iSLN block can be effectively and safely applied to relieve POST after intubation of DLTs on thoracic surgery. TRIAL REGISTRATION: The study protocol was registered at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , NO. ChiCTR2000032188, 22/04/2020).

Epidemiological and Whole-Genome Sequencing Analysis of a Gastroenteritis Outbreak Caused by a New Emerging Serotype of Vibrio parahaemolyticus in China.

Vibrio parahaemolyticus is an important foodborne pathogen with diverse serotypes. In May 2021, we investigated a gastroenteritis outbreak that occurred in China, caused by V. parahaemolyticus O10:K4 infection. Based on the epidemiological curve, this outbreak was identified as a homologous exposure event. A case-control study demonstrated that emperor crab with mashed garlic (odds ratio [OR] = 4.60, p = 0.030; 95% confidence interval [95% CI]: 1.11-19.14), goose liver geoduck (OR = 4.50, p = 0.029; 95% CI: 1.12-18.13), shrimp (OR = 4.89, p = 0.021; 95% CI: 1.22-19.65), and sea cucumber (OR = 7.36, p = 0.005; 95% CI: 1.68-32.26) were the potential sources of the food poisoning. V. parahaemolyticus isolates from 18 laboratory-confirmed cases were all serotyped O10:K4, and determined to be sequence type ST3 via multilocus sequence typing. Pulsed field gel electrophoresis and whole-genome sequencing analysis revealed the identical pattern and 0-2 single nucleotide variation among these isolates. tdh was positive in all isolates, while trh and Orf8 were absent. Seven essential base positions in toxRS for pandemic clone identification were identical between the O10:K4 and O3:K6 pandemic clones. Phylogenetic analysis with 45 additional genomes of 13 different serotypes showed the closest genetic relationship between O10:K4 and O1: KUT. O10:K4 was thought to evolve from the O3:K6 pandemic clone. The new serovariant of O3:K6 poses a challenge for the prevention and control of V. parahaemolyticus disease outbreaks, or even epidemics, in the future.