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In this study, the keyhole dynamic behavior and molten pool flow were investigated to elucidate the effects of oscillating laser on porosity in narrow-gap oscillating laser-MIG hybrid welding of aluminum alloys. A weld with a porosity of 0.08% was produced at the laser oscillating frequency of 600 Hz and diameter of 1 mm, while 2.27% without oscillating laser. Compared to non-oscillating laser, keyhole opening size increased by about 2.3 times and keyhole depth fluctuation was suppressed. The forces acted on the interface between keyhole wall and molten pool became more balanced. The increased vapor recoil pressure overcame the combined closure effect of gravity and molten pool pressure. While applying oscillating laser, the vortex in molten pool was eliminated and the liquid metal flow was more stable. The combined impact force caused by droplets transfer and liquid metal convection due to constraining effect of narrow gap was buffered, which had less effect on molten pool and keyhole stability. The liquid metal tended to flow from the molten pool inside to surface, which favored the escape of bubbles from the molten pool.

Abstract Background Tissue plasminogen activator (tPA) is recommended as the preferred thrombolytic therapy for acute myocardial infarction (AMI). This study aimed to explore tPA-related adverse events (AEs) reported in the United States Food and Drug Administration Adverse Event Reporting System (FAERS), assess the potential safety of three preferred tPA therapies for treating AMI, and provide guidance for selecting tPA for prehospital thrombolysis. Method Four algorithms, including ROR, PRR, BCPNN, and MGPS, were used to quantify the signals of Tenecteplase, Reteplase, and Alteplase related AEs and compare the differential degrees of the three tPA-associated AEs in the actual data. Result We detected 18 signals of Tenecteplase-induced AE, 29 signals of Reteplase-induced AE, and 22 signals of Alteplase-induced AE. Among the three drugs, Tenecteplase had the highest signal intensity for intracranial hemorrhage-related AE, followed by Alteplase. Besides, Reteplase had the highest signal intensity for procedure-related AE and Alteplase had the highest signal intensity for arrhythmia-related AE. The time-onset analysis indicates that we should be vigilant for AEs, especially within the first week and the first 1–2 days after medication. Conclusion This study identified and compared the signals of AE related to Tenecteplase, Reteplase, and Alteplase in AMI patients.

Abstract Background Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality. Methods To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion IHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy. Results Capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib in both models. The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib extended survival and induced long-term progression-free survival when combined with radiotherapy in two complementary mouse models. Capmatinib treatment increased radiation-induced DNA double-strand breaks and delayed their repair. Conclusions We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies, and insights into molecular mechanism underlying increased efficacy. Taken together, we demonstrate the groundbreaking efficacy of capmatinib and radiation as a highly promising concept for future clinical trials.

Abstract Cadmium (Cd) is a neurotoxic contaminant that induces cognitive decline similar to that observed in Alzheimer's disease (AD). Autophagic flux dysfunction is attributed to the pathogenesis of AD, and this study aimed to investigate the effect of autophagy on environmental Cd‐induced AD progression and the underlying mechanism. Here, Cd exposure inhibited autophagosome‐lysosome fusion and impaired lysosomal function, leading to defects in autophagic clearance and then to APP accumulation and nerve cell death. Proteomic analysis coupled with Ingenuity Pathway Analysis (IPA) identified SIRT5 as an essential molecular target in Cd‐impaired autophagic flux. Mechanistically, Cd exposure hampered the expression of SIRT5, thus increasing the succinylation of RAB7A at lysine 31 and inhibiting RAB7A activity, which contributed to autophagic flux blockade. Importantly, SIRT5 overexpression led to the restoration of autophagic flux blockade, the alleviation of Aβ deposition and memory deficits, and the desuccinylation of RAB7A in Cd‐exposed FAD4T mice. Additionally, SIRT5 levels decrease mainly in neurons but not in other cell clusters in the brains of AD patients according to single‐nucleus RNA sequencing data from the public dataset GSE188545. This study reveals that SIRT5‐catalysed RAB7A desuccinylation is an essential adaptive mechanism for the amelioration of Cd‐induced autophagic flux blockade and AD‐like pathogenesis.

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors, leading to progressive photoreceptor loss. Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival. This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation (tcES) in mice affected by inherited retinal degeneration. Additionally, the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans. In this study, we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular, sine, and ramp waveforms. To investigate the functional effects of electrical stimulation on photoreceptors, we used human retinal explant cultures and rhodopsin knockout (Rho–/–) mice, demonstrating progressive photoreceptor degeneration with age. Human retinal explants isolated from the donors’ eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro. Photoreceptor density was evaluated by rhodopsin immunolabeling. In vivo Rho–/– mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms. Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response (OMR), respectively. Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas. Oscilloscope recordings indicated effective delivery of rectangular, sine, and ramp waveforms to the retina by transcorneal electrical stimulation, of which the ramp waveform required the lowest voltage. Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes. The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro (~0.5–1.5°C). Electrical stimulation increased photoreceptor survival in human retinal explant cultures, particularly at the ramp waveform. Transcorneal electrical stimulation (rectangular + ramp) waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results. Histology and immunolabeling demonstrated increased photoreceptor survival, improved outer nuclear layer thickness, and increased bipolar cell sprouting in Rho–/– mice. These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina, improves photoreceptor survival in both human and mouse retinas, and increases visual function in Rho–/– mice. Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.

Purpose: Renal interstitial fibrosis is a pathological manifestation of the progression of diabetic kidney disease (DKD). Dendrobium officinale polysaccharides (DOP), one of the major active components of Dendrobium officinale, have hypoglycemic and hypolipidemic effects and are used clinically to treat diabetes. However, the role of DOP in delaying DKD progression remains unclear. This study aimed to explore the potential mechanisms by which DOP delays DKD renal interstitial fibrosis. Methods: Using db/db mice as a model of DKD, we administered DOP by gavage and observed its therapeutic effectiveness. Employing ASO technology, we knocked down lncRNA XIST expression in kidney tissues and detected the expression of lncRNA XIST, TGF-β1, and renal interstitial fibrosis-related molecules. Results: DOP was primarily composed of monosaccharides, with 91.57% glucose and 1.41% mannose, forming a spheroid-like structure. It has a high polydispersity index with an Mw/Mn of 6.146, and the polysaccharides are mainly connected by 4-Man(p) and 4-Glc(p) linkages. In the kidneys of db/db mice, lncRNA XIST and TGF-β1 are highly expressed; however, their expression is significantly reduced after gastric infusion with DOP, and upon knockdown of lncRNA XIST, it might delay the progression of renal interstitial fibrosis in DKD. Conclusion: DOP may delay the progression of DKD renal interstitial fibrosis through the regulation of the LncRNA XIST/TGF-β1 related fibrotic pathway. This provides a new perspective for clinical strategies to delay the progression of DKD renal interstitial fibrosis.

Deep neural networks must address the dual challenge of delivering high-accuracy predictions and providing user-friendly explanations. While deep models are widely used in the field of time series modeling, deciphering the core principles that govern the models’ outputs remains a significant challenge. This is crucial for fostering the development of trusted models and facilitating domain expert validation, thereby empowering users and domain experts to utilize them confidently in high-risk decision-making contexts (e.g., decision-support systems in healthcare). In this work, we put forward a deep prototype learning model that supports interpretable and manipulable modeling and classification of medical time series (i.e., ECG signal). Specifically, we first optimize the representation of single heartbeat data by employing a bidirectional long short-term memory and attention mechanism, and then construct prototypes during the training phase. The final classification outcomes (i.e., normal sinus rhythm, atrial fibrillation, and other rhythm) are determined by comparing the input with the obtained prototypes. Moreover, the proposed model presents a human–machine collaboration mechanism, allowing domain experts to refine the prototypes by integrating their expertise to further enhance the model’s performance (contrary to the human-in-the-loop paradigm, where humans primarily act as supervisors or correctors, intervening when required, our approach focuses on a human–machine collaboration, wherein both parties engage as partners, enabling more fluid and integrated interactions). The experimental outcomes presented herein delineate that, within the realm of binary classification tasks—specifically distinguishing between normal sinus rhythm and atrial fibrillation—our proposed model, albeit registering marginally lower performance in comparison to certain established baseline models such as Convolutional Neural Networks (CNNs) and bidirectional long short-term memory with attention mechanisms (Bi-LSTMAttns), evidently surpasses other contemporary state-of-the-art prototype baseline models. Moreover, it demonstrates significantly enhanced performance relative to these prototype baseline models in the context of triple classification tasks, which encompass normal sinus rhythm, atrial fibrillation, and other rhythm classifications. The proposed model manifests a commendable prediction accuracy of 0.8414, coupled with macro precision, recall, and F1-score metrics of 0.8449, 0.8224, and 0.8235, respectively, achieving both high classification accuracy as well as good interpretability.

Abstract Lithium‐ion batteries (LIBs) have monopolized energy storage markets in modern society. The reliable operation of LIBs at cold condition (

Abstract Background Enterovirus (EV) infections are being increasingly seen in younger infants, often being more severe than in older children. The risk factors of EV infection in infants have been inadequately investigated till date. Methods We conducted a retrospective study on hospitalized children with laboratory-confirmed EV infection (50 infants aged 0–3 months and 65 older than 3 months) at a tertiary care center in China. Prevalence, clinical characteristics, and genetic features of the virus were analyzed, and independent predictors for severe infection were assessed. Results Clinical findings showed that severe infection was more common in infants aged 0–3 months than in older children (78.0% vs. 35.4%, p

Abstract Lithium‐ion batteries (LIBs) with fast‐charging capabilities have the potential to overcome the “range anxiety” issue and drive wider adoption of electric vehicles. The U.S. Advanced Battery Consortium has set a goal of fast charging, which requires charging 80% of the battery's state of charge within 15 min. However, the polarization effects under fast‐charging conditions can lead to electrode structure degradation, electrolyte side reactions, lithium plating, and temperature rise, which are highly linked to the thermodynamic and kinetic properties of electrolytes. The conventional nonaqueous electrolytes used in LIBs consist of carbonate and cannot support fast‐charging without compromising performance and lifespan. This review outlines the challenges of fast‐charging LIBs and the requirements of electrolytes suitable for fast‐charging. Additionally, recent developments in fast‐charging electrolytes from four key perspectives: electrolyte additives, low‐viscosity co‐solvents, high concentration or localized high‐concentration electrolytes, and advanced electrolytes are summarized. Furthermore, this review provides insights for the design of fast‐charging electrolytes based on the mechanism of charging process and offers an overview of the current state and future direction of the field.

Biodegradable magnesium alloy stents have great application potential in the treatment of cardiovascular diseases. However, bare magnesium alloy stents are still limited by some problems such as too fast degradation, poor hemocompatibility, and inability to regulate the behaviors of vascular cells in clinical applications. Surface modifications are highly requested to improve the corrosion resistance and biocompatibility of magnesium alloy stents. Herein, a fucoidan-based coating consisting of MgF2 layer, polydopamine (PDA) and fucoidan was constructed on Mg-Zn-Y-Nd (ZE21B) alloy to improve its corrosion resistance, hemocompatibility and rapid endothelialization for vascular stent application. Compared to bare ZE21B alloy, the modified ZE21B alloy exhibited better corrosion resistance and hemocompatibility. More importantly, the endothelial cells (ECs) and smooth muscle cells (SMCs) exhibited a distinct dose-dependent behaviors towards the fucoidan grafting density. The relatively low fucoidan grafting density promoted the proliferation, spreading and migration of ECs, but suppressed these behaviors of SMCs. The results of in vivo implantation experiments indicated that the fucoidan-based coating modified ZE21B alloy can inhibit intimal hyperplasia, relieve tissue inflammation, and promote the rapid endothelialization. Thus, the fucoidan-based coating provides a simple and effective strategy to develop novel magnesium alloy stents with improved corrosion resistance, good hemocompatibility and pro-endothelialization potential.

Abstract Background Currently, there is no generally approved surgical treatment for patients with primary angle-closure glaucoma (PACG) and co-existing cataracts. The aim of this systematic review and meta-analysis was to compare the efficacy and safety of phacoemulsification and phacotrabeculectomy in PACG patients with cataract. Methods Diverse databases were searched, including PubMed, MEDLINE, EMBASE, Cochrane Library, Chinese Journal Full-text Database (CNKI), Wanfang database, and China Science and Technology Journal Database, for randomized controlled trials (RCTs) on phacoemulsification and phacotrabeculectomy for the treatment of PACG published up to 30 June 2021. ReviewManager (RevMan) version 5.4 software was used for the meta-analysis, and the effective quantity of measurement data was measured by the mean difference (MD) and 95% confidence interval (CI). The effect of counting data was measured by odds ratio (OR). Results Our search of the databases identified 14 RCTs that satisfied the search criteria. Meta-analysis of these 14 RCTs showed that at the 1 month postoperative follow-up, intraocular pressure (IOP) of patients in the phacoemulsification group was higher than that of patients in the phacotrabeculectomy group (MD 2.04, 95% CI 1.42–2.65; P

AbstractThe intention of this study was to explore whether it is feasible to use a heterotrophic nitrifying-aerobic denitrifying strain to bio-enhance the biological contact oxidation process. In this experiment, Acinetobacter sp. RW, a highly efficient heterotrophic nitrifying-aerobic denitrifying strain isolated in the laboratory, was used as the functional strain. The results show that part of the NH4+-N (ammonia nitrogen), TN (total nitrogen) and CODCr (dichromate oxidizability) of the sewage could be effectively removed via the biological contact oxidation process performed in the laboratory. Average removal ratios of NH4+-N, TN and CODCr increased by 32.8%, 4.33% and 11.13%, respectively, after biological enhancement of RW. According to the biodiversity information, Acinetobacter exhibited the greatest change at the genus level in both the water and biofilm after adding the strain RW. In the 12 days without RW addition, the treatment efficiency of the device was only 1.01% different from that during daily dosing. The results demonstrate that the treatment efficiency of the process can be improved by adding RW. RW can effectively adhere to the biofilm and become one of the dominant strains. Therefore, we conclude that the biological contact oxidation process bio-enhanced by RW was successful and has practical potential.

The use of electrochemical energy storage systems based on alkali metal electrodes is hindered by the dendrites’ growth and volume changes upon cycling. Here, the authors propose nitrogen and zinc co-doped porous carbon nanofibers as potassium metal hosting material for reversible metal deposition.

Abstract Despite wide‐temperature tolerance and high‐voltage compatibility, employing propylene carbonate (PC) as electrolyte in lithium‐ion batteries (LIBs) is hampered by solvent co‐intercalation and graphite exfoliation due to incompetent solvent‐derived solid electrolyte interphase (SEI). Herein, trifluoromethylbenzene (PhCF3), featuring both specific adsorption and anion attraction, is utilized to regulate the interfacial behaviors and construct anion‐induced SEI at low Li salts’ concentration (

Microplastics (MPs) are emerging contaminants that pose a global threat to the environment. Mangrove ecosystems, which contribute to biogeochemical cycles, are vulnerable to various anthropogenic disturbances and chemical pollutants. In this study, the abundance and the characteristics of MPs were investigated in 10 species of benthic organisms, including crabs, bivalves, and snails, from seven typical mangrove distribution areas, with a total of 15 sampling sites in Hainan, South China. The abundance of MPs in each sampling site ranged between 0.83 ± 1.32 and 12.00 ± 0.00 items/individual, with an average of 3.90 ± 3.31 items/individual, while the abundance of MPs varied between 0.17 and 2.00 items/individual for the different species. Fibers (80.13%) were the most abundant MPs, most of the MPs were brown (37.18%) or blue (26.64%), and more than 80% were small-sized plastic (

Lithium halide electrolytes show great potential in constructing high-energy-density solid-state batteries with high-voltage cathode materials due to their high electrochemical stability and wide voltage windows. However, the high cost and low conductivity of some compositions inhibit their applications. Moreover, the effect of electronic additives in the cathode mixture on the stability and capacity is unclear. Here, the Y3+ doping strategy is applied to enhance the conductivity of low-cost Li2ZrCl6 electrolytes. By tailoring the Y3+ dopant in the structure, the optimal Li2.5Zr0.5Y0.5Cl6 with high conductivity up to 1.19 × 10−3 S cm−1 is obtained. Li2.5Zr0.5Y0.5Cl6@CNT/Li2.5Zr0.5Y0.5Cl6/Li5.5PS4.5Cl1.5/In-Li solid-state batteries with different carbon nanotube (CNT) contents in the cathode are fabricated. The stability and electrochemical performances of the cathode mixture as a function of CNT content are studied. The cathode mixture containing 2% (wt.) CNT exhibits the highest stability and almost no discharge capacity, while the cathode mixture consisting of Li2.5Zr0.5Y0.5Cl6 and 10% (wt.) CNT delivers a high initial discharge capacity of 199.0 mAh g−1 and reversible capacities in the following 100 cycles. Multiple characterizations are combined to unravel the working mechanism and confirm that the electrochemical reaction involves the 2-step reaction of Y3+/Y0, Zr4+/Zr0, and Cl−/Clx− in the Li2.5Zr0.5Y0.5Cl6 electrolyte. This work provides insight into designing a lithium halide electrolyte-based cathode mixture with a high ionic/electronic conductive framework and good interfacial stability for solid-state batteries.

Background. In this meta-analysis, we aimed to systematically compare the efficacy and safety of phacoemulsification and laser peripheral iridotomy (LPI) in the treatment of primary angle-closure glaucoma (PACG). Method. We searched PubMed, MEDLINE, EMBASE, the Cochrane Library, the Chinese Journal Full-text Database (CNKI), the Wanfang database, and the China Science and Technology Journal Database for randomized controlled trials (RCTs) of phacoemulsification and LPI in the treatment of PACG published up to September 30, 2022. Postoperative intraocular pressure (IOP), anterior chamber depth (ACD), complications, corneal endothelial cell count, and best-corrected visual acuity (BCVA) were compared. The effective quantity of measurement data was measured by the mean difference (MD) and 95% confidence interval (CI). The effect of counting data was measured by the odds ratio (OR). Result. A total of 1731 potential studies were identified, and after screening, 8 RCT studies were included. The results of the meta-analysis showed that, compared to the LPI group, the patients in the phacoemulsification group showed lower IOP six and twelve months after operation (MD-3.39, 95% CI −4.15∼−2.63, P

PurposeThis study aimed to investigate the causal association between unhealthy lifestyle factors and diabetic retinopathy (DR) risk and to determine better interventions targeting these modifiable unhealthy factors.DesignTwo-sample Mendelian randomization (MR) analysis was performed in this study. The inverse variance-weighted method was used as the primary method.MethodOur study included 687 single-nucleotide polymorphisms associated with unhealthy lifestyle factors as instrumental variables. Aggregated data on individual-level genetic information were obtained from the corresponding studies and consortia. A total of 292,622,3 cases and 739,241,18 variants from four large consortia (MRC Integrative Epidemiology Unit [MRC-IEU], Genetic Investigation of Anthropometric Traits [GIANT], GWAS & Sequencing Consortium of Alcohol and Nicotine Use [GSCAN], and Neale Lab) were included.ResultIn the MR analysis, a higher body mass index (BMI) (odds ratio [OR], 95% confidence interval [CI] = 1.42, 1.30–1.54; P < 0.001] and cigarettes per day (OR, 95% CI = 1.16, 1.05–1.28; P = 0.003) were genetically predicted to be causally associated with an increased risk of DR, while patients with higher hip circumference (HC) had a lower risk of DR (OR, 95% CI = 0.85, 0.76–0.95; P = 0.004). In the analysis of subtypes of DR, the results of BMI and HC were similar to those of DR, whereas cigarettes per day were only related to proliferative DR (PDR) (OR, 95% CI = 1.18, 1.04–1.33; P = 0.009). In the MR-PRESSO analysis, a higher waist-to-hip ratio (WHR) was a risk factor for DR and PDR (OR, 95% CI = 1.24, 1.02–1.50, P = 0.041; OR, 95% CI = 1.32, 1.01–1.73, P = 0.049) after removing the outliers. Furthermore, no pleiotropy was observed in these exposures.ConclusionOur findings suggest that higher BMI, WHR, and smoking are likely to be causal factors in the development of DR, whereas genetically higher HC is associated with a lower risk of DR, providing insights into a better understanding of the etiology and prevention of DR.

All-solid-state lithium sulfide batteries exhibit great potential as next-generation energy storage devices due to their low cost and high energy density. However, the poor conductivity of the solid electrolytes and the low electronic conductivity of sulfur limit their development. In this work, the highly conductive Li7P3S11 glass-ceramic solid electrolyte with room temperature conductivity of 1.27 mS cm−1 is synthesized and combined with the FeS2 cathode and Li-In anode to fabricate FeS2/Li7P3S11/Li-In all-solid-state Li-S battery. The assembled battery delivers high initial discharge capacities of 620.8, 866.4 mAh g−1, and 364.8 mAh g−1 at 0.1C under room temperature, 60°C and 0°C, respectively. It shows a discharge capacity of 284.8 mAh g−1 with a capacity retention of 52.4% after 80 cycles at room temperature. When the operating temperature rises to 60°C, this battery suffers a fast decay of capacity in 40 cycles. However, this battery sustains a high discharge capacity of 256.6 mAh g−1 with a capacity retention of 87.9% after 100 cycles under 0°C, smaller volume expansion of ASSBs at 0°C keep the solid/solid contact between the electrolyte particles, thus resulting in better electrochemical performances. EIS and in situ pressure characterizations further verify that the differences of electrochemical performances are associated with the volume variations caused by the temperature effects. This work provides a guideline for designing all-solid-state Li-S which is workable in a wide temperature range.

Objective To analyze the characteristics and influencing factors of blood transfusion in patients undergoing hepatectomy with hydatid hepatica, so as to provide perioperative blood security of these patients. Methods A retrospective analysis was performed on 40 hydatid hepatica patients who underwent hepatectomy from June 2011 to June 2021, and they were divided into the transfusion group (n=15) and the non-transfusion group (n=25). The difference in basic information, operative information, blood routine, coagulation function, biochemical parameters and thromboelastogram between the two groups were compared, and the characteristics of perioperative blood transfusion were analyzed. Results Fifteen(37.5%, 15/40) patients undergoing hepatectomy received blood transfusion, among which 2(5%, 5/40), 10(25%, 10/40) and 11(27.5%, 11/40) received preoperative, intraoperative and postoperative transfusion, respectively. The average transfusion of suspended red blood cells, plasma and cryoprecipitate were 4.77 U, 1 355 mL and 11.9 U respectively, without any adverse reactions of blood transfusion occurred. The operative time, intraoperative blood loss, the number of patients with tumor diameter ≥10 cm/ diameter

Objective The study aim was to evaluate the clinical outcomes, functional outcomes, and postoperative complications of anchor and Krackow‐“8” suture fixation (AS) and K‐wire fixation in patients with distal pole patellar fractures. Methods Twenty‐eight patients with distal pole patella fractures between January 2011 and December 2014 were reviewed retrospectively. The anchor and Krackow‐“8” suture fixation (AS group) was applied in 10 patients and 18 patients underwent K‐wire fixation (K‐wire group). The average age of patients was 46.000 ± 19.476 years in the AS group and 47.556 ± 15.704 years in the K‐wire group, with comparable demographic characteristics. All patients underwent regular follow‐up the operative data and postoperative functional and clinical outcomes were recorded. Complications were recorded by clinical and radiographic assessment. Bostman patellar fracture functional score was used to evaluate knee function after patellar fracture. Results A total of 28 eligible patients were included in this study. The mean follow‐up was similar for the AS and the K‐wire groups (P > 0.05). The incision length of AS group was significantly smaller than that of K‐wire group (P < 0.05). The incision length of AS group was significantly smaller than that of K‐wire group (P < 0.05). The final follow‐up on the range of motion of the knee: the average extension lag was similar in two groups (P > 0.05); flexion and flexion–extension angle was slightly better in the AS group than in the K‐wire group. The Bostman patella fracture functional score of AS group were better than K‐wire group at 3 and 6 months after operation. Four kinds of postoperative complications in two groups, one patient (10%) in the AS group and two patients (11.1%) in the K‐wire group had infections. Two (11.1%) cases of nonunion in group K and three patients (16.7%) required re‐operation: one due to infection and two due to early implant failure. In the AS group, all distal pole fractures of the patella showed bony union, without loosening, falling, pulling out and nonunion of the fractures 6 months after operation. Conclusions Anchor and Krackow‐“8” suture fixation is an easily executed surgical procedure that can significantly reduce incision length and achieve better surgical outcomes than traditional procedures with regard to postoperative complications, knee function and without requiring a second operation. This technique is an effective operation method for the treatment of inferior patellar pole fractures.

Objective To evaluate the treatment effects of the reinforced Ma‐Griffith method combined with a minimally invasive small incision(M‐G/MISI) in the treatment of acute Achilles tendon rupture. Methods From January 2012 to January 2020, a retrospective study was carried out on thirty‐one patients with acute Achilles tendon ruptures that were treated using the M‐G/MISI. Patient with acute Achilles tendon rupture was operated on in the prone position. The M‐G/MISI begin with making a small incision to debride the stumps of ruptured tendon. Then M‐G/MISI was used to suture the distal and proximal Achilles tendons with the help of a epidural puncture needle and polydioxanone synthetic absorbable suture (PDS) Ⅱ line. Finally the stumps of ruptured tendon was reattached. After the surgery, the affected limb was fixed with either a plaster slab below the knee brace or a functional brace. Removal of plaster external fixation and partial weight‐bearing with crutches five weeks after the operation; Complete weight‐bearing nine weeks after the operation; jogging permitted 12 weeks after the operation; Patients were allowed to resume normal activities six months after the operation. Results All 31 patients in this study were male. Nineteen of these patients had Achilles tendon rupture on the right lower extremity, while 12 had ruptures on the left lower extremity. The patients had a mean age of 33.35 ± 7.13 years (range, 18‐52 years). The mean operation time was 79.58 ± 22.67 minutes (range, 40‐167 minutes). The mean time from injury to operation was 4.19 ± 2.01 days (range, 1‐8 days), and the mean hospital stay was 9.87 ± 3.88 days (range, 5‐22 days). The new technique had a small incision with a mean length of 3.94 ± 1.82 cm (range, 2‐6 cm). The mean intraoperative blood loss was 16.77 ± 13.76 mL (range, 10‐50 mL) and the mean follow‐up time was 21.35 ± 10.18 months (range, 6‐50 months). No wound infection, fistula, skin necrosis, sural nerve damage, deep venous thrombosis or tendon re‐rupture was found. One year after the surgery, all patients reported 97.00 (range, 93‐100 points) AOFAS ankle‐hindfoot score points and the mean ATRS was 97.39 (range, 91‐100) points. Conclusion The reinforced Ma‐Griffith method, combined with a minimally invasive small incision suture, is a simple, effective, minimally invasive technique and low‐cost surgical method for the treatment of acute Achilles tendon rupture.

PurposeThe aim of this study was to improve the intratumoral accumulation of an antibody–drug conjugate (ADC) and minimize its off-target toxicity, SKB264, a novel anti-trophoblast antigen 2 (TROP2) ADC that was developed using 2-methylsulfonyl pyrimidine as the linker to conjugate its payload (KL610023), a belotecan-derivative topoisomerase I inhibitor. The preclinical pharmacologic profiles of SKB264 were assessed in this study.MethodsThe in vitro and in vivo pharmacologic profiles of SKB264, including efficacy, pharmacokinetics–pharmacodynamics (PK-PD), safety, and tissue distribution, were investigated using TROP2-positive cell lines, cell-derived xenograft (CDX), patient-derived xenograft (PDX) models, and cynomolgus monkeys. Moreover, some profiles were compared with IMMU-132.ResultsIn vitro, SKB264 and SKB264 monoclonal antibody (mAb) had similar internalization abilities and binding affinities to TROP2. After cellular internalization, KL610023 was released and inhibited tumor cell survival. In vivo, SKB264 significantly inhibited tumor growth in a dose-dependent manner in both CDX and PDX models. After SKB264 administration, the serum or plasma concentration/exposure of SKB264 (conjugated ADC, number of payload units ≥1), total antibody (Tab, unconjugated and conjugated mAb regardless of the number of the payload units), and KL610023 in cynomolgus monkeys increased proportionally with increasing dosage from 1 to 10 mg/kg. The linker stability of SKB264 was significantly enhanced as shown by prolonged payload half-life in vivo (SKB264 vs. IMMU-132, 56.3 h vs. 15.5 h). At the same dose, SKB264’s exposure in tumor tissue was 4.6-fold higher than that of IMMU-132.ConclusionsCompared with IMMU-132, the longer half-life of SKB264 had a stronger targeting effect and better antitumor activity, suggesting the better therapeutic potential of SKB264 for treating TROP2-positive tumors.

Cadmium (Cd), which is considered an endocrine disruptor, has been linked to the onset of breast cancer (BC). Our recent study demonstrated that Cd-induced BC progression has a strong correlation with miR-374c-5p dysregulation. The aim of our work was to investigate other potential miRNAs involved in Cd-induced BC cell proliferation and metastasis. In our study, the miRNA profiles of Cd-treated T-47D cells (10 μM, 72 h) were analyzed by miRNA-seq, and our results confirmed that miR-3614–5p was the top downregulated miRNA. Moreover, miR-3614–5p mimic transfection significantly decreased the proliferative ability, migration and invasive ability of BC cell lines (T-47D and MCF-7). Furthermore, we analyzed the overlapping genes from our RNA-seq data and predicted targets from the mirDIP database, and twelve genes (ALDH1A3, FBN1, GRIA3, NOS1, PLD5, PTGER4, RASGRF2, RELN, RNF150, SLC17A4, TG, and TXNRD1) were identified as potential binding targets of miR-3614–5p in the current model. Nonetheless, only miR-3614–5p inhibition caused an increase in TXNRD1 expression upon Cd exposure in T-47D and MCF-7 cell lines. Importantly, luciferase reporter assays further verified that miR-3614–5p suppressed the expression of TXNRD1 by directly binding to the 3′-untranslated region (UTR), and TXNRD1 inhibition significantly repressed the proliferation and metastasis capacity of BC cells upon Cd exposure. Together, our findings demonstrated that Cd exposure repressed the expression of miR-3614–5p, thus activating TXNRD1 expression, which promoted the abnormal proliferation and metastasis of BC cells.

Bovine herpesvirus type 1 (BHV-1) causes bovine respiratory disease that poses a significant threat to the cattle industry. The prevalence of BHV-1 has recently increased in China. However, the lack of information about the prevalent isolates limits the control of the disease. In this study, a novel strain of BHV-1 was isolated from nasal swabs of Holstein cows in 2020 in China, designated as BHV SHJS. The genome of BHV strain SHJS is 135, 102 bp in length and highly similar to strain SP1777 (KM258883.1) with an identity of 99.64%. Mutations, insertions, or deletions mainly occur in UL27, UL44, and US8, etc., relative to the different genomic coordinates. Phylogenetic tree of UL44 (gC) showed that BHV strain SHJS belongs to BHV-1.2b cluster. The result showed that the strain had a different evolutionary origin from those prevalent in China. This study will enrich our knowledge regarding BHV outbreak strains in China and contribute to the prevention and pathogenic studies of BHV-1.2.

Patient-derived xenografts provide a resource for basic and translational cancer research. Here, the authors generate multiple pediatric high-grade glioma xenografts, use omics technologies to show that they are representative of primary tumours and use them to assess therapeutic response.

Genogroup II genotype 4 (GII.4) norovirus causes acute gastroenteritis in children, and its infection is more severe than that of other genotypes. Early and precise detection and treatment are critical for controlling its spread and reducing the severity of infection. In this study, a rapid and efficient isothermal assay for the GII.4 norovirus detection (GII.4-CRISPR detection) was developed based on the CRISPR/Cas13a system. The assay can be applied without expensive instrumentation, and the results can be read via both fluorescence and lateral flow strip (LFS). The analytical sensitivity of this assay was 5 copies/reaction, and there was no cross-reaction with other genotypes of norovirus or other clinically common pathogens. There was a coincidence rate of 100% between our assay and commercial quantitative polymerase chain reaction. GII.4-CRISPR detection improves upon the shortcomings of some previously established molecular methods of detection, particularly with regard to accessibility. It provides an alternative tool for outbreak control and early diagnosis of GII.4 norovirus infection.

Fluoride has received much attention for its predominant bone toxicity in the human body. However, the toxic mechanism of bone injury caused by fluoride exposure remains largely unclear. Bone marrow mesenchymal stem cells (BMSCs) are widely used as model cells for evaluating bone toxicity after environmental toxicant exposure. In this study, BMSCs were exposed to fluoride at 1, 2, and 4 mM for 24 h, and fluoride significantly inhibited cell viability at 2 and 4 mM. A multiomics analysis combining transcriptomics with metabolomics was employed to detect alterations in genes and metabolites in BMSCs treated with 2 mM fluoride. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of transcriptomics profiles identified “lysosomes” as the top enriched pathway, which was severely damaged by fluoride exposure. Lysosomal damage was indicated by decreases in the expression of lysosomal associated membrane protein 2 (LAMP 2) and cathepsin B (CTSB) as well as an increase in pH. Upregulation of the lysosome-related genes Atp6v0b and Gla was observed, which may be attributed to a compensatory lysosomal biogenesis transcriptional response. Interestingly, inhibition of glutathione metabolism was observed in fluoride-treated BMSCs at the metabolomic level. Moreover, an integrative analysis between altered genes, metabolites and lysosome signaling pathways was conducted. Palmitic acid, prostaglandin C2, and prostaglandin B2 metabolites were positively associated with Atp6v0b, a lysosome-related gene. Overall, our results provide novel insights into the mechanism responsible for fluoride-induced bone toxicity.

Objective To explore the corresponding strategies of blood preparation for placenta previa operation in our hospital according to the situation of blood transfusion during and after operation. Methods Ninety pregnant women with placenta previa (complete, partial or marginal) undergoing the caesarean operation and blood transfusion in our hospital from January 2011 to September 2020 were selected as the research objects. The corresponding data about intraoperative/postoperative blood loss, blood transfusion and blood preparation were collected, analyzed and compared. Results There was no significant differences in age between complete and marginal placenta previa(P>0.05), but significant differences in intraoperative/postoperative blood loss and the units of blood transfusion (P1 000 mL). The difference between ordering and transfusion units of complete and marginal placenta previa were 0.4 and 0, respectively. When the complete placenta previa was accompanied by placenta increta or placenta percreta, the blood loss was larger (>1 000 mL) and the units of blood transfusion ranged from 4.5 U to 6 U, while the blood loss was generally low (≤1 000 mL) and the units of blood transfusion was concentrated at 3 (2, 4) U without placenta accreta nor implantation.The difference between ordering and transfusion units of complete placenta previa with non-implantation, placenta accreta, placenta increta and placenta percreta were 0.165, 0.33, 0.5 and 1, respectively. Conclusion For marginal placenta previa, 3U blood is recommended for routine preparation, 3U blood for complete placenta previa with non-implantation or placenta accrete, and 4.5-6U for complete placenta previa with placenta increta or placenta percreta.

Epstein–Barr virus (EBV) is a prevalent human gamma-herpesvirus that infects the majority of the adult population worldwide and is associated with several lymphoid and epithelial malignancies. EBV displays a biphasic life cycle, namely, latent and lytic replication cycles, expressing a diversity of viral proteins. Among the EBV proteins being expressed during both latent and lytic cycles, the oncogenic roles of EBV lytic proteins are largely uncharacterized. In this review, the established contributions of EBV lytic proteins in tumorigenesis are summarized according to the cancer hallmarks displayed. We further postulate the oncogenic properties of several EBV lytic proteins by comparing the evolutionary conserved oncogenic mechanisms in other herpesviruses and oncoviruses.

Abstract Background Tourniquets are widely used in total knee arthroplasty (TKA), but the issue of their safety remains controversial. Previous studies have focused on TKA blood loss, duration of surgery, and hemostatic drugs. The purpose of this meta-analysis was to analyze the effect of tourniquet use on postoperative deep venous thrombosis (DVT). Methods PubMed, SCOPUS, Web of Science, Embase, and the Cochrane Library were searched for randomized clinical trials published before April 17, 2020, that compared the effect of tourniquet use on postoperative DVT, knee circumference, D-dimers, and pain measured using the visual analog scale (VAS). Results Fourteen clinical trials that included 1321 unique participants were included in the meta-analysis. Among the total, 721 and 600 participants were randomized to the tourniquet and non-tourniquet groups, respectively. The incidence of postoperative thrombosis in the tourniquet group was significantly higher than in the non-tourniquet group (RR 2.30, 95% CI 1.51–3.49, P < 0.0001, I 2 = 0%). On the 1st, 3rd, and 5th to 21st days, and 3 to 6 weeks after surgery, the knee circumference difference of the tourniquet group was significantly larger than that of the non-tourniquet group (P < 0.05). However, 4 to 6 months after the surgery, no significant difference in knee circumference was found between the two groups (MD 0.14, 95% CI −0.02–0.31, P = 0.09, I 2 = 0%). The VAS score of the tourniquet group was higher than the non-tourniquet group on the 3rd and 5th days after surgery (P < 0.05). However, this difference was not significant (MD 0.31, 95% CI −0.05–0.66, P = 0.09, I 2 = 89%). Conclusion Results of this meta-analysis indicate that tourniquet application could increase the incidence of postoperative DVT and aggravate postoperative pain and swelling in the short term. Level of evidence Level III

Abstract All‐solid‐state (ASS) Na–S batteries are promising for a large‐scale energy‐storage system owing to numerous merits. However, the high conversion reaction barrier impedes their practical application. In this work, the basic mechanism on how Se catalyzes the conversion reaction in the Na–S batteries is unraveled. The sodiation/desodiation of Na–SeS2 nanobatteries are systematically evaluated via in situ transmission electron microscopy (in situ TEM) with a microheating device. The real‐time analyses reveal an amorphous Na–SexSy intermediate phase appears during the direct conversion from SeS2 to Na2S, and a reverse reaction succeeds at 100 °C with a prior formation of Se. The absence of polysulfides and a much lower desodiation temperature in contrast to Na–S nanobatteries demonstrate that the Se incorporation significantly lowers the conversion reaction barrier. According to these findings, the ASS SeS2 batteries using a Na3SbS4 solid electrolyte (SE) are assembled using various SE:C ratios in the composite cathodes to investigate the effect of the ion and electron transport on the electrochemical properties, including the effective transport properties, MacMullin number, and the tortuosity factor. The obtained results in turn confirm the findings from the in situ TEM. These findings are applicable to optimize other S‐based active materials and improve their utilization.

Antibiotic residue may pose a serious risk to aquaculture, and the culture of Litopenaeus vannamei in a low-salinity environment is a growing trend over the world. Here, we aimed to understand the combined effect of low salinity and sulfamethoxazole (SMZ) and florfenicol (FLO) antibiotics on L. vannamei. The growth performance, immune functions, antioxidant capacity and intestinal microbiota were investigated. Compared with the control group, the weight gain and survival rate significantly decreased (p < 0.05) in shrimp after they were exposed to low-salinity (salinity 3) water and the mixture of antibiotics and low-salt conditions for 28 days. The antioxidant activities of SOD and T-AOC, shown at low salinity and in the higher concentration of the SMZ treatment group (SMZH), were significantly decreased, while the GST activity was significantly increased in each treatment group in comparison with the control group. The expression of immune-related genes, including TOLL, LvIMD, PPO and HSP, in the low concentration of the SMZ treatment group (SMZL) was higher than that in the other groups. The diversity of intestine microbiota was disturbed with a lower Shannon index in the low-salinity and SMZH groups, and a higher Simpson index in the SMZH group. Proteobacteria, Actinobacteria and Bacteroidetes were the dominant phyla in the gut of L. vannamei. At the genus level, Microbacterium, Shewanella, Aeromonas, Acinetobacter, Gemmobacter, Paracoccus and Lysobacter were significantly decreased in the low-salinity group. However, the abundance of opportunistic pathogens belonging to the genus Aeromonas in the FLO group was increased. The predicted microbe-mediated functions showed that the pathway for “amino acid metabolism” and “replication and repair” was significantly inhibited in both the low-salinity and antibiotic-exposed groups. All the findings in this study indicate that the combined effect of antibiotics and low salinity on L. vannamei negatively impacted the physiological and intestinal microbiota functions.

Microspinel LiMn2O4 (LMO) is a widely used cathode material in power lithium-ion batteries. However, inevitable Mn dissolution and dynamic phase instability will cause the degradation of microspinel LMO during cycling. Here, a low-tortuosity LMO (LMO-LT) electrode is fabricated by an ice-templating method, which exhibits enhanced dynamic phase stability, alleviated Mn dissolution, and rare particle microcracks during cycling. It is shown that the low-tortuosity electrode enables fast lithium-ion diffusion and thus small concentration polarization, leading to uniform electrochemical reaction within microregions of the LMO-LT electrode. Furthermore, the fast lithium-ion transport kinetics and even mesoscopic scale reactions of the LMO-LT electrode effectively alleviate irreversible phase transition and Mn dissolution as well as suppress crack generation in LMO particles. As a result, the full cell [negative-to-positive capacity ratio (N/P) = 1.1] with thick LMO-LT cathode (13 mg cm−2) and Li4Ti5O12 anode sustains 80.0% capacity over 200 cycles. The LMO-LT electrode further delivers 78.9% capacity of that at 0.1 C at the high rate of 5 C. This work provides an important strategy to enhance dynamic phase stability and suppress Mn dissolution at the mesoscopic scale, promoting the development of high-performance LMO electrodes.

Cadmium (Cd) is a toxic heavy metal that can facilitate the development and progression of breast cancer (BC). Emerging evidence has indicated that the progression of Cd-exposed BC is related to the dysregulation of microRNAs (miRNAs). The purpose of our study was to investigate the expression pattern and underlying mechanisms of miR-374c-5p in Cd-mediated BC progression. In this study, T-47D cells and MCF-7 cells were treated with different concentrations of Cd (0.1, 1 and 10 μM) for 72 h. MiR-374c-5p expression was downregulated, and transfection of miR-374c-5p mimics significantly decreased BC cell proliferation, migration and invasion induced by 10 μM Cd. Importantly, we used the Cytoscape software plugin cytoHubba to analyse the intersected genes between our RNA-Seq results and the mirDIP database, and six hub genes (CNR1, CXCR4, GRM3, RTN1, SLC1A6 and ZEB1) were identified as potential direct targets of miR-374c-5p in our model; however, luciferase reporter assays indicated that miR-374c-5p only repressed GRM3 by directly binding to its 3′-untranslated region (UTR). Of note, we verified that suppression of N6-methyladenosine (m6A) modification led to miR-374c-5p downregulation by decreasing its RNA transcript stability. Together, these findings demonstrated that m6A modification of pri-miRNA-374c blocks miRNA-374c-5p maturation and then activates GRM3 expression, which drives BC cell metastasis after Cd exposure.

Summary: Developing low cost, yet high-voltage electrolyte is significant to improve the energy density and practicability of lithium metal batteries (LMBs). Low concentration electrolyte has significant merits in terms of cost and viscosity; however, their poor compatibility with high-voltage LMBs hinders its applications. Here, we develop a diluted low concentration electrolyte by replacing solvating cosolvent with a non-solvating cosolvent to facilitate the interaction between BF4− and Li+, resulting in optimized interfacial chemistry and suppressed side reaction. Thus, the high-loading Li-LiCoO2 full cells (20.4 mg cm−2) deliver outstanding cycling stability and rate performance at a cutoff voltage of 4.6 V. More impressively, a Li-LiCoO2 pouch cell achieves an energy density of more than 400 Wh kg−1 under practical conditions with thin Li (50 μm) and lean electrolyte (2.7 g Ah−1). This work provides a rational approach to design a low concentration electrolyte, which can be extended to other high voltage battery systems.

Abstract Background Hand, foot, and mouth disease (HFMD) is a common infectious disease occurring in children under 5 years of age worldwide, and Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA-16) are identified as the predominant pathogens. In recent years, Coxsackievirus A6 (CVA-6) and Coxsackievirus A10 (CVA-10) have played more and more important role in a series of HFMD outbreaks. This study aimed to understand the epidemic characteristics associated with HFMD outbreak in Guangzhou, 2018. Methods The clinical and laboratory data of 1220 enterovirus-associated HFMD patients in 2018 were analysed in this study. Molecular diagnostic methods were performed to identify its serotypes. Phylogenetic analyses were depicted based on the complete VP1 gene. Results There were 21 enterovirus serotypes detected in Guangzhou in 2018. Three serotypes of enterovirus, CVA-6 (364/1220, 29.8%), CVA-10 (305/1220, 25.0%), and CVA-16 (397/1220, 32.5%), were identified as the causative pathogens and accounted for 87.3% among all 1220 HFMD patients. In different seasons, CVA-6 was the predominant pathogen of HFMD during autumn, and CVA-10 as well as CVA-16 were more prevalent in summer. Patients infected by CVA-6, CVA-10 or CVA-16 showed similar clinical features and laboratory characteristics, and the ratios of severe HFMD were 5.8, 5.9, and 1.5% in the three serotypes. Phylogenetic analyses of VP1 sequences showed that the CVA-6, CVA-10, and CVA-16 sequences belonged to the sub-genogroup E2, genogroup E, and genogroup B1, respectively. Conclusions CVA-6, CVA-10, and CVA-16 were the predominant and co-circulated serotypes in Guangzhou China, 2018, which should be the new target for prevention and control of HFMD. Our findings provide useful information for diagnosis, treatment, and prevention of HFMD.

Cadmium (Cd) is a carcinogen that stimulates breast cancer (BC) progression. Rapamycin is a macrolide antibiotic produced by Streptomyces hygroscopicus that possesses a wide array of pharmacological activities, including anti-BC activity. However, the effects of rapamycin on Cd-increased BC progression and the underlying mechanism have not been fully elucidated. Here, we hypothesize that rapamycin antagonizes Cd-induced BC cell proliferation and metastasis by directly modulating ACSS2. In this study, we found that rapamycin efficiently inhibited Cd-induced proliferation, invasion and migration in MCF-7 and T47-D cells. Moreover, a surface plasmon resonance (SPR) assay confirmed that rapamycin directly binds to the ACSS2 protein with a calculated equilibrium dissociation constant (KD) of 18.3 μM. Molecular docking showed that there are three binding sites in the ACSS2 protein and that rapamycin binds at the coenzyme A (COA) binding site with a docking score of − 12.26 and a binding free energy of − 26.34 kcal/mol. More importantly, rapamycin suppresses Cd-induced BC progression by activating ACSS2. After cells were cotreated with an ACSS2 inhibitor, the effects of rapamycin were abolished. In conclusion, our findings suggest that rapamycin suppresses Cd-augmented BC progression by upregulating ACSS2, and ACSS2 may serve as a direct target of rapamycin for inhibiting xenobiotic (e.g., Cd)-mediated BC progression.

This data set contains the data used in Twarog et al. (2021) to examine the robustness and utility of response surface models in drug combination analysis. It includes simulated experimental data for the evaluation of traditional index methods, as well as a processed library of interaction metrics evaluated on the Merck OncoPolyPharmacology Screen (O'Neil et al., 2016), the scripts used to implement those metrics on all tested combinations in that screen, and scripts to evaluate the performance of those metrics in comparison with real-world mechanistic classifications. Finally, the data set includes data from several published and unpublished drug combination experiments, and scripts which allow the analyses of those experiments to be replicated and applied to new data.

Collaborative simultaneous localization and mapping have a great impact on various applications such as search-and-rescue and agriculture. For each agent, the key to performing collaboration is to measure the motion relative to other participants or external anchors; currently, this is mainly accompanied by (1) matching to the shared maps from other agents or (2) measuring the range to anchors with UWB devices. While requiring multiple agents to visit the same area can decrease the task efficiency and anchors demand a distribution process, this paper proposes to use a monocular camera, an inertial measurement unit (IMU), and a UWB device as the onboard sensors on each agent to build an accurate and efficient centralized collaborative SLAM system. For each participant, visual-inertial odometry is adopted to estimate the motion parameters and build a local map of the explored areas. The agent-to-agent range is measured by the onboard UWB and is published to the central server together with the estimated motion parameters and the reconstructed maps. We designed a global optimization algorithm to make use of the cross-agent map match information detected by a visual place technique, and the agent-to-agent range information to optimize the motion parameter of all the participants and merge the local maps into a global map. Compared with existing collaborative SLAM systems, the proposed system can perform collaboration with onboard UWB measurements only, vision only, and a combination of these; this greatly improves the adaptiveness and robustness of the collaborative system. We also present an in-depth analysis of C2VIR-SLAM in multiple UAV real-flight datasets.

Modern healthcare practice, especially in intensive care units, produces a vast amount of multivariate time series of health-related data, e.g., multi-lead electrocardiogram (ECG), pulse waveform, blood pressure waveform and so on. As a result, timely and accurate prediction of medical intervention (e.g., intravenous injection) becomes possible, by exploring such semantic-rich time series. Existing works mainly focused on onset prediction at the granularity of hours that was not suitable for medication intervention in emergency medicine. This research proposes a Multi-Variable Hybrid Attentive Model (MVHA) to predict the impending need of medical intervention, by jointly mining multiple time series. Specifically, a two-level attention mechanism is designed to capture the pattern of fluctuations and trends of different time series. This work applied MVHA to the prediction of the impending intravenous injection need of critical patients at the intensive care units. Experiments on the MIMIC Waveform Database demonstrated that the proposed model achieves a prediction accuracy of 0.8475 and an ROC-AUC of 0.8318, which significantly outperforms baseline models.

Glycan molecules can be modified directly on the cell surface via chemoenzymatic approaches. Here, the authors employ a set of four bacterial glycosyltransferases to develop a live cell-based killing assay to probe host cell glycan-mediated influenza A virus infection.

Lithium sulfur batteries are promising for advanced energy storage, but polysulfide shuttling limits performance lifetime. Here the authors report selenium-doping in a sulfur-based cathode to prevent dissolution of polysulfide intermediates, leading to ether compatibility, high capacity and stable cycling.

Abstract Background The flag leaf of rice (Oryza sativa L.) is an important determinant of plant type characteristics and grain yield. Identification of flag leaf mutants of rice is crucial to elucidate the molecular mechanism of flag-leaf development, and for exploitation of rice germplasm resources. Results In this study, we describe a mutant designated short and narrow flag leaf 1 (snfl1). Histological analysis showed that the length of epidermal cells and number of longitudinal veins were decreased in the flag leaf of the snfl1 mutant. Map-based cloning indicated that a member of the GATA family of transcription factors is a candidate gene for SNFL1. A single-nucleotide transition at the last base in the single intron of snfl1 led to variation in alternative splicing and early termination of translation. Complemented transgenic plants harbouring the candidate SNFL1 gene rescued the snfl1 mutant. Analysis of RT-PCR and the SNFL1 promoter by means of a GUS fusion expression assay showed that abundance of SNFL1 transcripts was higher in the culm, leaf sheath, and root. Expression of the SNFL1-GFP fusion protein in rice protoplasts showed that SNFL1 was localized in nucleus. Conclusions We conclude that SNFL1 is an important regulator of leaf development, the identification of which might have important implications for future research on GATA transcription factors.

Hand, foot, and mouth disease (HFMD) is a common infectious disease affecting mainly children under 5 years of age. Coxsackievirus A6 (CVA-6), a major causative pathogen of HFMD, has caused outbreaks in recent years. Currently, no effective vaccine or antiviral treatments are available. In this study, one-step reverse-transcription recombinase polymerase amplification (RT-RPA), combined with a disposable lateral flow strip (LFS) assay, was developed to detect CVA-6. This assay can be performed in less than 35 min at 37°C without expensive instruments, and the result can be observed directly with the naked eye. The sensitivity of the RT-RPA-LFS was 10 copies per reaction, which was comparable to that of the conventional real-time quantitative polymerase chain reaction (qPCR) assays. Moreover, the assay specificity was 100%. The clinical performance of the RT-RPA-LFS assay was evaluated using 142 clinical samples, and the coincidence rate between RT-RPA-LFS and qPCR was 100%. Therefore, our RT-RPA-LFS assay provides a simple and rapid approach for point-of-care CVA-6 diagnosis.

Moderate curling generally causes upright leaf blades, which favors the establishment of ideal plant architecture and increases the photosynthetic efficiency of the population, both of which are desirable traits for super hybrid rice (Oryza sativa L.). In this study, we identified a novel curled-leaf mutant, curled flag leaf 2 (cfl2), which shows specific curling at the base of the flag leaf owing to abnormal epidermal development, caused by enlarged bulliform cells and increased number of papillae with the disordered distribution. Map-based cloning reveals that CFL2 encodes a cytochrome P450 protein and corresponds to the previously reported OsCYP96B4. CFL2 was expressed in all analyzed tissues with differential abundance and was downregulated in the clf1 mutant [a mutant harbors a mutation in the homeodomain leucine zipper IV (HD-ZIP IV) transcription factor Roc5]. Yeast one-hybrid and transient expression assays confirm that Roc5 could directly bind to the cis-element L1 box in the promoter of CFL2 before activating CFL2 expression. RNA sequencing reveals that genes associated with cellulose biosynthesis and cell wall-related processes were significantly upregulated in the cfl2 mutant. The components of cell wall, such as lignin, cellulose, and some kinds of monosaccharide, were altered dramatically in the cfl2 mutant when compared with wild-type “Jinhui10” (WT). Taken together, CFL2, as a target gene of Roc5, plays an important role in the regulation of flag leaf shape by influencing epidermis and cell wall development.