Vertical MoS2 transistors with sub-1-nm gate lengths.

Ultra-scaled transistors are of interest in the development of next-generation electronic devices1-3. Although atomically thin molybdenum disulfide (MoS2) transistors have been reported4, the fabrication of devices with gate lengths below 1 nm has been challenging5. Here we demonstrate side-wall MoS2 transistors with an atomically thin channel and a physical gate length of sub-1 nm using the edge of a graphene layer as the gate electrode. The approach uses large-area graphene and MoS2 films grown by chemical vapour deposition for the fabrication of side-wall transistors on a 2-inch wafer. These devices have On/Off ratios up to 1.02 × 105 and subthreshold swing values down to 117 mV dec-1. Simulation results indicate that the MoS2 side-wall effective channel length approaches 0.34 nm in the On state and 4.54 nm in the Off state. This work can promote Moore's law of the scaling down of transistors for next-generation electronics.

Programmable Ferroelectricity in Hf0.5Zr0.5O2 Enabled by Oxygen Defect Engineering.

Ferroelectricity, especially the Si-compatible type recently observed in hafnia-based materials, is technologically useful for modern memory and logic applications, but it is challenging to differentiate intrinsic ferroelectric polarization from the polar phase and oxygen vacancy. Here, we report electrically controllable ferroelectricity in a Hf0.5Zr0.5O2-based heterostructure with Sr-doped LaMnO3, a mixed ionic-electronic conductor, as an electrode. Electrically reversible extraction and insertion of an oxygen vacancy into Hf0.5Zr0.5O2 are macroscopically characterized and atomically imaged in situ. Utilizing this reversible process, we achieved multilevel polarization states modulated by the electric field. Our study demonstrates the usefulness of the mixed conductor to repair, create, manipulate, and utilize advanced ferroelectric functionality. Furthermore, the programmed ferroelectric heterostructures with Si-compatible doped hafnia are desirable for the development of future ferroelectric electronics.

Mitigation of ROS-triggered endoplasmic reticulum stress by upregulating Nrf2 retards diabetic nephropathy.

Endoplasmic reticulum stress (ERS) plays a crucial role in the pathogenesis of diabetic nephropathy (DN), and it is often accompanied by an increase in reactive oxygen species (ROS) production. However, the precise relationship between NFE2-related factor-2 (Nrf2), a key regulator of ROS balance, and ERS in DN remains elusive. This study aimed to investigate the impact of Nrf2 on ERS and its therapeutic potential in DN. Herein, ERS-related changes, including increased activating transcription factor-6 (ATF6), glucose-regulated protein 78 (GRP78), and transcription factor C/EBP homologous protein (CHOP) expression, were observed in the renal tissues of streptozotocin-induced DN mice and high glucose cultured human renal proximal tubular (HK-2) cells. Nrf2 knockdown increased the sensitivity of HK-2 cells to ERS under high glucose conditions, underscoring the regulatory role of Nrf2 in ERS modulation. Notably, upregulating Nrf2 in ezetimibe-treated diabetic mice restored ERS markers and ameliorated albuminuria, glomerular hypertrophy, mesangial expansion, and tubulointerstitial fibrosis. Furthermore, the inhibition of ERS in HK-2 cells by the ROS scavenger, N-acetylcysteine, highlights the interplay between ROS and ERS. This study, for the first time, elucidates that the upregulation of Nrf2 may alleviate the negative influence of ROS-mediated ERS, presenting a promising therapeutic avenue for delaying the progression of DN. These findings suggest a potential strategy for targeting Nrf2 and ERS in developing novel therapeutic interventions for DN.

Social, Behavioral, and Metabolic Risk Factors and Racial Disparities in Cardiovascular Disease Mortality in U.S. Adults : An Observational Study.

BACKGROUND: Cardiovascular disease (CVD) mortality is persistently higher in the Black population than in other racial and ethnic groups in the United States. OBJECTIVE: To examine the degree to which social, behavioral, and metabolic risk factors are associated with CVD mortality and the extent to which racial differences in CVD mortality persist after these factors are accounted for. DESIGN: Prospective cohort study. SETTING: NHANES (National Health and Nutrition Examination Survey) 1999 to 2018. PARTICIPANTS: A nationally representative sample of 50 808 persons aged 20 years or older. MEASUREMENTS: Data on social, behavioral, and metabolic factors were collected in each NHANES survey using standard methods. Deaths from CVD were ascertained from linkage to the National Death Index with follow-up through 2019. RESULTS: Over an average of 9.4 years of follow-up, 2589 CVD deaths were confirmed. The age- and sex-standardized rates of CVD mortality were 484.7 deaths per 100 000 person-years in Black participants, 384.5 deaths per 100 000 person-years in White participants, 292.4 deaths per 100 000 person-years in Hispanic participants, and 255.1 deaths per 100 000 person-years in other race groups. In a multiple Cox regression analysis adjusted for all measured risk factors simultaneously, several social (unemployment, low family income, food insecurity, lack of home ownership, and unpartnered status), behavioral (current smoking, lack of leisure-time physical activity, and sleep <6 or >8 h/d), and metabolic (obesity, hypertension, and diabetes) risk factors were associated with a significantly higher risk for CVD death. After adjustment for these metabolic, behavioral, and social risk factors separately, hazard ratios of CVD mortality for Black compared with White participants were attenuated from 1.54 (95% CI, 1.34 to 1.77) to 1.34 (CI, 1.16 to 1.55), 1.31 (CI, 1.15 to 1.50), and 1.04 (CI, 0.90 to 1.21), respectively. LIMITATION: Causal contributions of social, behavioral, and metabolic risk factors to racial and ethnic disparities in CVD mortality could not be established. CONCLUSION: The Black-White difference in CVD mortality diminished after adjustment for behavioral and metabolic risk factors and completely dissipated with adjustment for social determinants of health in the U.S. population. PRIMARY FUNDING SOURCE: National Institutes of Health.

Accelerated Fibrosis Progression of Diabetic Nephropathy From High Uric Acid's Activation of the ROS/NLRP3/SHP2 Pathway in Renal Tubular Epithelial Cells Under High Glucose Conditions.

Context: Elevated uric-acid levels in the blood are closely associated with hypertension, metabolic syndrome, diabetic nephropathy, cardiovascular diseases, and chronic kidney disease (CKD). A high-glucose diet promotes the accumulation of uric acid. Fibrosis commonly occurs in patients with late-stage type 1 or 2 diabetes and can lead to organ dysfunction. Objective: The study intended to investigate whether high uric acid under high glucose conditions can promote the fibrotic progression of diabetic nephropathy by activating the reactive oxygen species (ROS)/ "nod-like receptor (NLR) family pyrin domain containing 3" (NLRP3)/ "Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2" (SHP2) pathway, which can promote epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells. Design: The research team conducted an animal study. Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei Province, China. Animals: The animals were 14 healthy, male, C57BL/6J mice. Outcome Measures: The research team: (1) using Masson's trichrome staining, examined the fibrosis of renal, tubular epithelial cells in the streptozotocin (STZ) modeling and the STZ modeling + uric-acid groups; (2) used Western Blot analysis to detect the protein expression of NLRP3, "nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase 2" (NOX2), NOX4, alpha-smooth muscle actin (α-SMA), fibronectin 1 (FN-1), collagen-I, and mothers against decapentaplegic homolog 2/3 (SMAD2/3); (3) conducted in-vitro experiments by dividing transformed C3H mouse kidney-1 (TCMK-1) cells into different groups: STZ modeling group, STZ modeling + high-glucose group, STZ modeling + high-glucose + advanced glycation end (AGE) product group, STZ modeling+ high-glucose + AGE + uric-acid group, STZ modeling+ high glucose + SHP2 small interfering RNA (SiRNA) group, STZ modeling + high glucose + SHP2 SiRNA + AGE group, and STZ modeling+ high-glucose + SHP2 SiRNA + AGE + uric-acid group for Western Blot experiments; and (4) performed immunofluorescence, CCK-8, and transwell experiments on the seven groups of TCMK-1 cells with different treatments. Results: The STZ modeling + uric acid group's levels of fibrosis was significantly higher than that of the STZ modeling group (P < .01). Additionally, the STZ modeling + uric acid groups' expression of α-SMA, FN-1, collagen-I, P-SMAD2, P-SMAD3, NLRP3, and reactive oxygen species (ROS), EMT, and SMAD-related proteins were significantly higher than those of the STZ modeling group (P < .01). The protein expression of SHP2, P-SMAD2, α-SMA, and FN-1 for the STZ modeling + high glucose + SHP2 SiRNA, the STZ modeling + high glucose + SHP2 SiRNA + AGE, and the STZ modeling + high glucose + SHP2 SiRNA + AGE + uric acid groups were significantly lower than those of the STZ modeling + high glucose, STZ modeling + high glucose + AGE, and the STZ modeling + high glucose + AGE + uric acid groups, respectively. Immunofluorescence indicated that the STZ modeling+ high glucose + AGE + uric acid group had the highest relative fluorescence intensity, while the three groups treated with SHP2 SiRNA showed the least expression. The cell counting kit-8 (CCK-8) assay showed that STZ modeling group had less cell proliferation, STZ modeling + high sugar group had less cell proliferation than STZ modeling + high sugar +AGE group, STZ modeling + high sugar +AGE+ uric acid group had the highest cell proliferation, STZ modeling + high sugar +SHP2 SiRNA group and STZ modeling + high sugar +SHP2 SiRNA+AGE group and STZ modeling + high sugar +SHP2 SiRNA+AGE+ uric acid group showed the least number of cell proliferation. The results of the transwell cell migration assay were consistent with the CCK-8 assay. Conclusions: In a high-glucose environment, high uric acid can promote the fibrotic progression of diabetic nephropathy by activating the ROS/NLRP3/SHP2 pathway, leading to mesenchymal transition between renal tubular epithelial cells.

Membrane-Based Preparation Process and Antioxidant and Anti-AGEs Activities of a Novel Propolis Ultrafiltrate.

Propolis is one functional supplement with hundreds of years of usage. However, it's rarely consumed directly for its resinous property. Herein, a pre-treated process which can remove the impurity while preserve its bioactivities is needed to maximise its therapeutic opportunities. In the present study, a membrane-based ultrafiltration process was developed on a KM1812-NF experimental instrument. Using Brazilian green propolis as testing material, all experimental steps and parameters were sequentially optimized. In addition, a mathematical model was developed to fit the process. As a result, the optimum solvent was 60 % ethanol adjusted to pH 8-9, while the optimum MWCO (molecular weight cut-off) value of membrane was 30 KDa. The membrane filtration dynamic model fitted with the function y=(ax+b)/(1+cx+dx2 ). The resulting propolis ultrafiltrate from Brazilian green propolis, termed P30K, contains the similar profile of flavonoids and phenolic acids as raw propolis. Meanwhile, the ORAC (oxygen radical absorbance capacity) value of P30K is 11429.45±1557.58 µM TE/g and the IC50 value of inhibition of fluorescent AGEs (advanced glycation end products) formation is 0.064 mg/mL. Our work provides an innovative alternative process for extraction of active compounds from propolis and reveals P30K as an efficient therapeutic antioxidant.

PZT-Enabled MoS2 Floating Gate Transistors: Overcoming Boltzmann Tyranny and Achieving Ultralow Energy Consumption for High-Accuracy Neuromorphic Computing.

Low-power electronic devices play a pivotal role in the burgeoning artificial intelligence era. The study of such devices encompasses low-subthreshold swing (SS) transistors and neuromorphic devices. However, conventional field-effect transistors (FETs) face the inherent limitation of the "Boltzmann tyranny", which restricts SS to 60 mV decade-1 at room temperature. Additionally, FET-based neuromorphic devices lack sufficient conductance states for highly accurate neuromorphic computing due to a narrow memory window. In this study, we propose a pioneering PZT-enabled MoS2 floating gate transistor (PFGT) configuration, demonstrating a low SS of 46 mV decade-1 and a wide memory window of 7.2 V in the dual-sweeping gate voltage range from -7 to 7 V. The wide memory window provides 112 distinct conductance states for PFGT. Moreover, the PFGT-based artificial neural network achieves an outstanding facial-recognition accuracy of 97.3%. This study lays the groundwork for the development of low-SS transistors and highly energy efficient artificial synapses utilizing two-dimensional materials.

All Three AKT Isoforms Can Upregulate Oxygen Metabolism and Lactate Production in Human Hepatocellular Carcinoma Cell Lines.

Hepatocellular carcinoma (HCC), the main pathological type of liver cancer, is related to risk factors such as viral hepatitis, alcohol intake, and non-alcoholic fatty liver disease (NAFLD). The constitutive activation of the PI3K/AKT signaling pathway is common in HCC and has essential involvement in tumor progression. The serine/threonine kinase AKT has several downstream substrates, which have been implicated in the regulation of cellular metabolism. However, the contribution of each of the three AKT isoforms, i.e., AKT1, AKT2 and AKT3, to HCC metabolism has not been comprehensively investigated. In this study, we analyzed the functional role of AKT1, AKT2 and AKT3 in HCC metabolism. The overexpression of activated AKT1, AKT2 and AKT3 isoforms in the human HCC cell lines Hep3B and Huh7 resulted in higher oxygen consumption rate (OCR), ATP production, maximal respiration and spare respiratory capacity in comparison to vector-transduced cells. Vice versa, lentiviral vector-mediated knockdowns of each AKT isoform reduced OCR in both cell lines. Reduced OCR rates observed in the three AKT isoform knockdowns were associated with reduced extracellular acidification rates (ECAR) and reduced lactate production in both analyzed cell lines. Mechanistically, the downregulation of OCR by AKT isoform knockdowns correlated with an increased phosphorylation of the pyruvate dehydrogenase on Ser232, which negatively regulates the activity of this crucial gatekeeper of mitochondrial respiration. In summary, our data indicate that each of the three AKT isoforms is able to upregulate OCR, ECAR and lactate production independently of each other in human HCC cells through the regulation of the pyruvate dehydrogenase.

Efficacy and safety of tirofiban combined with endovascular therapy for basilar artery occlusion stroke due to large artery atherosclerosis.

BACKGROUND: This study aimed to evaluate the efficacy and safety of adjuvant tirofiban in patients with acute basilar artery occlusion due to large-artery atherosclerotic (LAA) receiving endovascular therapy (EVT). METHODS: This was a non-randomized, multicenter study using data from the Endovascular Treatment for Acute BASILAR Artery Occlusion (BASILAR) registry. Patients with acute basilar artery occlusion due to LAA within 24h of symptom onset who underwent EVT were included. Patients were divided into tirofiban and non-tirofiban groups according to whether tirofiban was used. The primary outcome was the ordinal modified Rankin scale score at 90 days. Safety outcomes were mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 h. RESULTS: A total of 417 patients were included, of whom 275 patients were in the tirofiban group and 142 patients in the non-tirofiban group. Compared with patients in the non-tirofiban group, patients in the tirofiban group were associated with a favorable shift in functional outcome at 90 days (6[4-6] vs 5 [2-6]; adjusted common OR, 2.51; 95 % CI, 1.64-3.83). The mortality was lower in the tirofiban group than the non-tirofiban group (40.7 % vs 58.5 %; adjusted OR, 0.35; 95 % CI, 0.21-0.56). The rate of sICH was 12.2 % in the non-tirofiban group and 5.2 % in the tirofiban group (adjusted OR, 0.37; 95 % CI, 0.17-0.80; P = 0.012). CONCLUSION: Tirofiban plus EVT might improve functional outcomes with a good safety for patients with acute basilar artery occlusion due to LAA. The results need to be confirmed in a randomized trial.

Overtone Mass Sensitivity of Quartz Crystal Microbalance Sensor with Asymmetric N-M Type Electrode Configuration.

Sensing sensitivity is one of the crucial parameters for quartz crystal microbalance (QCM) sensors. Herein, we study the overtone mass sensitivity of a QCM sensor with an asymmetric N-M type electrode configuration. In order to overcome the deficiency that the sensitivity of the QCM sensor with an asymmetric electrode cannot be calculated by Sauerbrey's equation, we design the electrochemical electrodeposition experiments to measure it. The measurement results of overtone mass sensitivities of three 3.1-5.1 and three 4.1-5.1 QCMs are 5.418, 5.629, and 5.572 Hz/ng and 4.155, 4.456, and 3.982 Hz/ng in the third overtone mode and 9.208, 9.474, and 9.243 Hz/ng and 6.811, 7.604, and 6.588 Hz/ng in the fifth overtone mode, respectively. The overtone mass sensitivities of three 5.1-5.1 QCMs are 3.210, 3.439, and 3.540 Hz/ng in the third overtone mode and 5.396, 5.010, and 5.707 Hz/ng in the fifth overtone mode, respectively. These results show that the overtone mass sensitivity of the N-M type QCM is larger than that of QCMs with symmetric electrodes, and the fifth overtone mass sensitivity is higher than the third overtone mass sensitivity for the same type of QCM. The above results strongly confirm that the overtone mass sensitivity of a QCM sensor with an asymmetric N-M electrode structure significantly enhances its sensing performance, and it will greatly meet the demands for high precision measurement of QCM sensors in applications.

Dual-function C2H2-type zinc-finger transcription factor GmZFP7 contributes to isoflavone accumulation in soybean.

Isoflavones are a class of secondary metabolites produced by legumes and play important roles in human health and plant stress tolerance. The C2H2 zinc-finger transcription factor (TF) functions in plant stress tolerance, but little is known about its function in isoflavone regulation in soybean (Glycine max). Here, we report a C2H2 zinc-finger TF gene, GmZFP7, which regulates isoflavone accumulation in soybean. Overexpressing GmZFP7 increased the isoflavone concentration in both transgenic hairy roots and plants. By contrast, silencing GmZFP7 expression significantly reduced isoflavone levels. Metabolomic and qRT-PCR analysis revealed that GmZFP7 can increase the flux of the phenylpropanoid pathway. Furthermore, dual-luciferase and electrophoretic mobility shift assays showed that GmZFP7 regulates isoflavone accumulation by influencing the expression of Isoflavone synthase 2 (GmIFS2) and Flavanone 3 ß-hydroxylase 1 (GmF3H1). In this study, we demonstrate that GmZFP7 contributes to isoflavone accumulation by regulating the expression of the gateway enzymes (GmIFS2 and GmF3H1) of competing phenylpropanoid pathway branches to direct the metabolic flux into isoflavone. A haplotype analysis indicated that important natural variations were present in GmZFP7 promoters, with P-Hap1 and P-Hap3 being the elite haplotypes. Our findings provide insight into how GmZFP7 regulates the phenylpropanoid pathway and enhances soybean isoflavone content.

MTGNN: Multi-Task Graph Neural Network based few-shot learning for disease similarity measurement.

Similar diseases are usually caused by molecular origins or similar phenotypes. Confirming the relationship between diseases can help researchers gain a deep insight of the pathogenic mechanisms of emerging complex diseases, and improve the corresponding diagnoses and treatment. Therefore, similar diseases are considerably important in biology and pathology. However, the insufficient number of labelled similar disease pairs cannot support the optimal training of the models. In this paper, we propose a Multi-Task Graph Neural Network (MTGNN) framework to measure disease similarity by few-shot learning. To tackle the problem of insufficient number of labelled similar disease pairs, we design the multi-task optimization strategy to train the graph neural network for disease similarity task (lack of labelled training data) by introducing link prediction task (sufficient labelled training data). The similarity between diseases can then be obtained by measuring the distance between disease embeddings in high-dimensional space learning from the double tasks. The experiment results evaluate the performance of MTGNN and illustrate its advantages over previous methods on few labeled training dataset.

Szechwan Lovage Rhizome Extract Improves Renal Function and Alleviates Inflammatory Responses in Pyelonephritis Rats Infected with Escherichia Coli via IL-6/STAT3 Axis.

The objective of this study was to probe the effect and mechanism of Szechwan Lovage Rhizome (Chuanxiong, CX) extract on renal function (RF) and inflammatory responses (IRs) in acute pyelonephritis (APN) rats infected with Escherichia coli (E. coli). Fifteen SD rats were randomized to intervention, model and control groups. Rats in the control were fed normally without treatment, rats in the APN model were infected with E. coli, and rats in the intervention group were intragastrically administered CX extract after infection with E. coli. HE staining detected pathological changes in the kidney tissues in rats. Levels of renal function indexes and inflammatory factors (IFs) were measured by ELISA and an automatic biochemical analyzer. Besides, levels of IL-6/signal transducer and activator of transcription 3 (STAT3) pathway-related genes in rat kidney tissue were detected by qRT-PCR and western blot. the experimental results showed that IL-1ß, IL-8, TNF-α and RF levels were the highest in the model group and the lowest in the control group, with those of the intervention group in between (P<0.05). Besides, the IL-6/STAT3 axis was markedly activated in the model group but inhibited in the intervention group (P<0.05). Subsequently, activated IL-6/STAT3 signal promoted IFs (IL-1ß, IL-8 and TNF-α) and RF (BUN, Scr, ß2-MG and UA), but this effect was offset after CX treatment (P<0.05). In conclusion, CX extract could improve RF and inhibit IRs of APN rats infected with E. coli by inhibiting the IL-6/STAT3 axis, which may be a new choice for APN treatment in the future.

Analysis of the improvement effect of Astragalus extract on oxidative stress injury in viral myocarditis through STAT3/IL-6.

The objective of this study was to investigate the improvement effect of Astragalus (AS) extract on oxidative stress (OS) and inflammatory response of myocarditis (MYO) cells through the STAT3/IL-6 axis. For this purpose, The MYO model cells prepared by intervening cardiomyocyte HL-1 with Coxsackievirus B3 (CVB3) were divided into four groups: model group, as well as high- (H-), medium- (M-) and low-dose (L-) AS groups treated by 80, 40, and 20 µg/mL AS, respectively. Conventionally cultured cells were set as the normal group. Cell multiplication and apoptosis, as well as levels of Myocardial injury markers (cTnT, BNP and CK), inflammatory cytokines (ICs; TNF-α, IL-1ß and IL-6) and OS indices (SOD, GSH-Px and MDA), were measured. STAT3/IL-6 pathway expression was also observed. Results showed that the model group presented decreased cell multiplication than the normal group, but with increased myocardial injury, apoptosis rate, Caspase3 protein, ICs and OS reaction (P < 0.05); In the three AS-intervened groups, enhanced cell multiplication, while reduced myocardial injury, apoptosis rate, ICs and OS response were observed, especially in H-AS group (P < 0.05). Besides, STAT3 and IL-6 concentrations, statistically increased in the model group, were reduced by AS intervention (P < 0.05). Colivelin, a specific activator of STAT3, further aggravated the apoptosis, inflammatory reaction and OS response of MYO cells (P < 0.05), but its impacts on MYO cells could be reversed by AS. In conclusion, AS can ameliorate MYO, and its mechanism is related to the inhibition of cellular inflammatory response and OS response through the STAT3/IL-6 axis.

High sensitivity graphene based health sensor with self-warning function.

In order to reduce the damage to people's health from diseases that attack the respiratory system such as COVID-19, asthma, and pneumonia, it is desired that patients' breathing can be monitored and alerted in real-time. The emergence of wearable health detection sensing devices has provided a relatively good response to this problem. However, there are still problems such as complex structure and poor performance. This paper introduces a laser-induced graphene (LIG) device that is attached to PDMS. The LIG is produced by laser irradiation of Nomex and subsequently transferred and attached to the PDMS. After being tested, it has demonstrated high sensitivity, stable tensile performance, good acoustic performance, excellent thermal stability, and other favorable properties. Notably, its gauge factor (GF) value can reach 721.67, which is quite impressive. Additionally, it is capable of emitting an alarm sound with an SPL close to 60 dB when receiving signals within the range of 5-20 kHz. The device realizes mechanical sensing and acoustic functions in one chip, and has a high application value in applications that need to combine sensing and early warning.

First Report of Leaf Spot Caused by Botrytis cinerea on Strawberry in China.

In the winter of 2022, circular or irregular leaf spots were observed on strawberry (Fragaria × ananassa) planted in commercial fields (cultivar 'xuetu', 'mengzhifu') in Yinzhou, Ningbo, Zhejiang, China (N29°48'48″, E121°39'47″), with disease incidence ranging from 10 to 15% in a field approximately 0.67 ha in size. The estimated crop loss associated with this disease was ~10%. Symptoms included circular or irregular lesions with brown halos and wheel marks, which eventually developed into leaf blight and petiole decay, but spore masses were seldom found on the leaf surface. In severe cases, leaves withered and abscissed. To isolate the causal agent, ten diseased leaves from ten different plants were collected, surface-sterilized with 75% ethanol for 50 s, rinsed twice with sterile distilled water, cut into small pieces (0.5 cm × 0.5 cm), and plated on potato dextrose agar (PDA), then incubated at 25°C in darkness for 5 days. Isolates , which displayed one kind of colony morphology were consistently obtained from each of the ten samples, and 58 single-conidium isolates with the same colony morphology were obtained. The isolation frequency was 58 of 60 samples. The colonies that grew on PDA produced white mycelia, which sporulated after 1 week, producing typical Botrytis-like gray spores. Three isolates (NBCM-1, NBCM-2, NBCM-3) were selected for identification and pathogenicity assays. Conidia were round to ellipsoid, 9.2 to 14.3 µm long (n=50), and 6.4 to 9.2 µm wide (n=50). Sclerotia were not observed on PDA. Based on these characteristics, the pathogen was tentatively identified as Botrytis cinerea (Zhang 2001). PCR was conducted for each of the three isolates to amplify the G3PDH, HSP60, RPB2, NEP1, and NEP2 genes, which are typically used for molecular identification of Botrytis species (Staats et al. 2005; Liu et al. 2016). The resulting amplicons were sequenced, and the sequences were processed using BLAST in the National Center for Biotechnology Information. Sequences of the three isolates were deposited in GenBank (accession nos. OR052082 to OR052086, OR493405 to OR493414). BLASTn analyses showed that isolates were 99 to 100% identical to B.cinerea reported causing leaf spot on strawberry in California; accession numbers MK919496 (G3PDH, 883/883 bp), MK919494 (HSP60, 992/992 bp), and MK919495 (RPB2, 1081/1081 bp). The resulting concatenated data set of G3PDH-HSP60-RPB2-NEP1-NEP2 was used to conduct a multilocus phylogenetic analysis (MLSA) using the maximum likelihood method. The MLSA tree indicated that the three isolates belonged to Botrytis cinerea. To test for pathogenicity, three 1-month-old strawberry (cultivar 'xuetu') plants were inoculated with each isolate (NBCM-1, NBCM-2, NBCM-3). A noninoculated control (sterile water only) was also included. The strawberry plants were inoculated by spraying with conidia suspension (1.0 × 105/ml) until run-off. Inoculations with sterile water served as controls. All plants were kept at 28/25°C (day/night), under a 12:12-h light/dark photoperiod. All plants were covered with transparent plastic bags to maintain humidity for the first 48 h, after which the bags were removed. After 4 to 7 days, leaf spot symptoms similar to those observed in the field were observed in all inoculated plants, while the controls remained healthy. The experiment was repeated three times. The pathogen was reisolated from the inoculated leaves and again identified as B. cinerea, with the same methodology used for the initial identification. Leaf spot caused by B. cinerea on strawberry was recently reported in California (Mansouripour and Holmes 2020) and Florida (Marin and Peres 2022). To our knowledge, this is the first report of B. cinerea causing leaf spot on strawberry in China. The pathogen is also the causal agent of Botrytis fruit rot on strawberry. Given the high variability of this pathogen (Marin and Peres 2022), further studies on its occurrence, spread, management, and control are required. The identification of this pathogen provides a basis for further research on its management and control.

Recent Progress of Tactile and Force Sensors for Human-Machine Interaction.

Human-Machine Interface (HMI) plays a key role in the interaction between people and machines, which allows people to easily and intuitively control the machine and immersively experience the virtual world of the meta-universe by virtual reality/augmented reality (VR/AR) technology. Currently, wearable skin-integrated tactile and force sensors are widely used in immersive human-machine interactions due to their ultra-thin, ultra-soft, conformal characteristics. In this paper, the recent progress of tactile and force sensors used in HMI are reviewed, including piezoresistive, capacitive, piezoelectric, triboelectric, and other sensors. Then, this paper discusses how to improve the performance of tactile and force sensors for HMI. Next, this paper summarizes the HMI for dexterous robotic manipulation and VR/AR applications. Finally, this paper summarizes and proposes the future development trend of HMI.

Biocompatible and Long-Term Monitoring Strategies of Wearable, Ingestible and Implantable Biosensors: Reform the Next Generation Healthcare.

Sensors enable the detection of physiological indicators and pathological markers to assist in the diagnosis, treatment, and long-term monitoring of diseases, in addition to playing an essential role in the observation and evaluation of physiological activities. The development of modern medical activities cannot be separated from the precise detection, reliable acquisition, and intelligent analysis of human body information. Therefore, sensors have become the core of new-generation health technologies along with the Internet of Things (IoTs) and artificial intelligence (AI). Previous research on the sensing of human information has conferred many superior properties on sensors, of which biocompatibility is one of the most important. Recently, biocompatible biosensors have developed rapidly to provide the possibility for the long-term and in-situ monitoring of physiological information. In this review, we summarize the ideal features and engineering realization strategies of three different types of biocompatible biosensors, including wearable, ingestible, and implantable sensors from the level of sensor designing and application. Additionally, the detection targets of the biosensors are further divided into vital life parameters (e.g., body temperature, heart rate, blood pressure, and respiratory rate), biochemical indicators, as well as physical and physiological parameters based on the clinical needs. In this review, starting from the emerging concept of next-generation diagnostics and healthcare technologies, we discuss how biocompatible sensors revolutionize the state-of-art healthcare system unprecedentedly, as well as the challenges and opportunities faced in the future development of biocompatible health sensors.

Diterpenoid alkaloids from Delphinium trichophorum.

Three new hetisine type C20-diterpenoid alkaloids, named as trichophorines A-C (1-3), were isolated from Delphinium trichophorum, together with nine known alkaloids (4-12). Their structures were elucidated on the basis of spectroscopic data (1D, 2D NMR, single-crystal X-ray, and HR-ESI-MS). All compounds were evaluated for the inhibitory activities against LPS induced NO production in RAW 264.7 macrophage cells, and none of them showed considerable inhibitory activity.

The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Metabolic reprogramming is considered a new hallmark of cancer, but it remains unclearly described in HCC. The dysregulation of the PI3K/AKT/mTOR signaling pathway is common in HCC and is, therefore, a topic of further research and the concern of developing a novel target for liver cancer therapy. In this review, we illustrate mechanisms by which this signaling network is accountable for regulating HCC cellular metabolism, including glucose metabolism, lipid metabolism, amino acid metabolism, pyrimidine metabolism, and oxidative metabolism, and summarize the ongoing clinical trials based on the inhibition of the PI3K/AKT/mTOR pathway in HCC.