SIRT3: A potential therapeutic target for liver fibrosis.

Sirtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase located in the mitochondria, which mainly regulates the acetylation of mitochondrial proteins. In addition, SIRT3 is involved in critical biological processes, including oxidative stress, inflammation, DNA damage, and apoptosis, all of which are closely related to the progression of liver disease. Liver fibrosis characterized by the deposition of extracellular matrix is a result of long termed or repeated liver damage, frequently accompanied by damaged hepatocytes, the recruitment of inflammatory cells, and the activation of hepatic stellate cells. Based on the functions and pharmacology of SIRT3, we will review its roles in liver fibrosis from three aspects: First, the main functions and pharmacological effects of SIRT3 were investigated based on its structure. Second, the roles of SIRT3 in major cells in the liver were summarized to reveal its mechanism in developing liver fibrosis. Last, drugs that regulate SIRT3 to prevent and treat liver fibrosis were discussed. In conclusion, exploring the pharmacological effects of SIRT3, especially in the liver, may be a potential strategy for treating liver fibrosis.

Intramolecular Quaternary Carbon Nitride Homojunction for Enhanced Visible Light Hydrogen Production.

In this work, an intramolecular carbon nitride (CN)-based quaternary homojunction functionalized with pyridine rings is prepared via an in situ alkali-assisted copolymerization strategy of bulk CN and 2-aminopyridine for efficient visible light hydrogen generation. In the obtained structure, triazine-based CN (TCN), heptazine-based CN (HCN), pyridine unit incorporated TCN, and pyridine ring inserted HCN constitute a special multicomponent system and form a built-in electric field between the crystalline semiconductors by the arrangement of energy band levels. The electron-withdrawing function of the conjugated heterocycle can trigger the skeleton delocalization and edge induction effect. Highly accelerated photoelectron-hole transfer rates via multi-stepwise charge migration pathways are achieved by the synergistic effect of the functional group modification and molecular quaternary homojunction. Under the addition of 5 mg 2-aminopyridine, the resulting homojunction framework exhibits a significantly improved hydrogen evolution rate of 6.64 mmol g-1 h-1 with an apparent quantum efficiency of 12.27% at 420 nm. Further, the catalyst verifies its potential commercial value since it can produce hydrogen from various real water environments. This study provides a reliable way for the rational design and fabrication of intramolecular multi-homojunction to obtain high-efficient photocatalytic reactions.

Long-term supplementation of genistein improves immune homeostasis in the aged gut and extends the laying cycle of aged laying hens.

Aging is associated with alterations in gut function, including intestinal inflammation, leaky gut, and impaired epithelial regeneration. Rejuvenating the aged gut is imperative to extend the laying cycle of aged laying hens. Genistein is known to have beneficial effects on age-related diseases, but its precise role in homeostasis of the aged gut of laying hens remains to be elucidated. In this study, 160 45-wk-old Hyline Brown laying hens were continuously fed a basal diet or a diet supplemented with 40 mg/kg genistein until they reached 100 wk of age. The results revealed that long-term genistein supplementation led to an improvement in the egg production rate and feed conversion ratio, as well as an increase in egg quality. Moreover, the expression levels of senescence markers, such as ß-galactosidase, P16, and P21, were decreased in the gut of genistein-treated aged laying hens. Furthermore, genistein ameliorated gut dysfunctions, such as intestinal inflammation, leaky gut, and impaired epithelial regeneration. Treg cell-derived IL-10 plays a crucial role in the genistein-induced regulation of age-related intestinal inflammation. This study demonstrates that long-term consumption of genistein improves homeostasis in the aged gut and extends the laying cycle of aged laying hens. Moreover, the link between genistein and Treg cells provides a rationale for dietary intervention against age-associated gut dysfunction.

Long-term immunogenicity and safety of heterologous boosting with a SARS-CoV-2 mRNA vaccine (SYS6006) in Chinese participants who had received two or three doses of inactivated vaccine.

The emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs booster vaccination. We evaluated the long-term safety and immunogenicity of heterologous boosting with a SARS-CoV-2 messenger RNA vaccine SYS6006. A total of 1000 participants aged 18 years or more who had received two (Group A) or three (Group B) doses of SARS-CoV-2 inactivated vaccine were enrolled and vaccinated with one dose of SYS6006 which was designed based on the prototype spike protein and introduced mutation sites. Adverse events (AEs) through 30 days and serious AEs during the study were collected. Live-virus and pseudovirus neutralizing antibody (Nab), binding antibody (immunoglobulin G [IgG]) and cellular immunity were tested through 180 days. Solicited all, injection-site and systemic AEs were reported by 618 (61.8%), 498 (49.8%), and 386 (38.6%) participants, respectively. Most AEs were grade 1. The two groups had similar safety profile. No vaccination-related SAEs were reported. Robust wild-type (WT) live-virus Nab response was elicited with peak geometric mean titers (GMTs) of 3769.5 (Group A) and 5994.7 (Group B) on day 14, corresponding to 1602.5- and 290.8-fold increase versus baseline, respectively. The BA.5 live-virus Nab GMTs were 87.7 (Group A) and 93.2 (Group B) on day 14. All participants seroconverted for WT live-virus Nab. Robust pseudovirus Nab and IgG responses to wild type and BA.5 were also elicited. ELISpot assay showed robust cellular immune response, which was not obviously affected by virus variation. In conclusion, SYS6006 heterologous boosting demonstrated long-term good safety and immunogenicity in participants who had received two or three doses of SARS-CoV-2 inactivated vaccine.

Temperature and light reverse the fertility of rice P/TGMS line ostms19 via reactive oxygen species homeostasis.

P/TGMS (Photo/thermo-sensitive genic male sterile) lines are crucial resources for two-line hybrid rice breeding. Previous studies revealed that slow development is a general mechanism for sterility-fertility conversion of P/TGMS in Arabidopsis. However, the difference in P/TGMS genes between rice and Arabidopsis suggests the presence of a distinct P/TGMS mechanism in rice. In this study, we isolated a novel P/TGMS line, ostms19, which shows sterility under high-temperature conditions and fertility under low-temperature conditions. OsTMS19 encodes a novel pentatricopeptide repeat (PPR) protein essential for pollen formation, in which a point mutation GTA(Val) to GCA(Ala) leads to ostms19 P/TGMS phenotype. It is highly expressed in the tapetum and localized to mitochondria. Under high temperature or long-day photoperiod conditions, excessive ROS accumulation in ostms19 anthers during pollen mitosis disrupts gene expression and intine formation, causing male sterility. Conversely, under low temperature or short-day photoperiod conditions, ROS can be effectively scavenged in anthers, resulting in fertility restoration. This indicates that ROS homeostasis is critical for fertility conversion. This relationship between ROS homeostasis and fertility conversion has also been observed in other tested rice P/TGMS lines. Therefore, we propose that ROS homeostasis is a general mechanism for the sterility-fertility conversion of rice P/TGMS lines.

Research on the Sensing Characteristics of an Integrated Grid-like Sensor Based on a Triboelectric Nanogenerator.

With the development of the integration and miniaturization of sensing devices, the concept of self-sensing devices has been proposed. A motion state is self-sensed via the structure or integration of an actuator in the construction of a sensing unit. This device is then used to capture the perception and measurement of states such as position, displacement, and speed. A triboelectric nanogenerator converts mechanical energy into electrical energy through the coupling effect of contact generation and electrostatic induction, which represents one of the reliable ways through which to realize integrated sensing. In this world, the power generation technology of the TENG is applied to a sensing device. The sensing characteristics of a grid-like TENG are designed and analyzed in freestanding triboelectric mode. Firstly, a relation model of displacement, velocity, voltage, and charge is established. The charge-transfer increment and current amounts are linearly related to the velocity. The open-circuit voltage has a positive relationship with the displacement. The maximum open-circuit voltage and the maximum charge transfer are fixed values, and they are only related to the inherent parameters of a triboelectric nanogenerator. Next, the sensor model is constructed using COMSOL Multiphysics 6.0. The simulation results show that the relationships between output voltage and charge transfer, as well as those between the increments of charge transfer, velocity, and displacement, are consistent with the results derived from the formula. Finally, a performance test of the designed sensor is carried out, and the results are consistent with the theoretical deduction and simulation. After analysis and processing of the output electrical signal by the host computer, it can feedback the frequency and speed value of the measured object. In addition, the output signal is stable, and there is no large fluctuation or attenuation during the 521-s vibration test. Because the working unit of the sensor is thin filmed, it is small in size, easy to integrate, and has no external power supply; moreover, it can be integrated into a device to realize the self-sensing of a motion state.

Two new 2-(2-phenylethyl)chromone derivatives and two sesquiterpenes from agarwood of Aquilaria sinensis with anti-inflammatory activity.

Two new 2-(2-phenylethyl)chromones (1-2), two new sesquiterpenes (12-13), and twelve known compounds (3-11, 14-16) were isolated from agarwood of Aquilaria sinensis. These structures were confirmed by HRESIMS, 1D and 2D NMR spectra. The absolute configurations of two new sesquiterpenes were determined by comparing the experimental and calculated ECD spectra. Among them, 7,8-dihydroxy-2-[2-(4'-methoxyphenyl)ethyl]chromone (2) was the first time found that the hydroxyl groups at both C-7/C-8 in agarwood. And Aseudesm B (13), the aldehyded methyl group at C-5 of eucalyptane sesquiterpenes was first discovered in natural products. In the bioassays, all compounds were evaluated for their inhibitory activity against lipopolysaccharide-activated nitric oxide (NO) production in RAW264.7 cells. Compounds 2-5, 7, 9-10, and 13-14 revealed notable inhibitory effects against NO production with IC50 values ranging from 4.0 to 13.0 µM.

Machine Learning-Based Predictive Models for 90-Day Readmission of Total Joint Arthroplasty Using Comprehensive Electronic Health Records and Patient-Reported Outcome Measures.

Background: The Centers for Medicare & Medicaid Services currently incentivizes hospitals to reduce postdischarge adverse events such as unplanned hospital readmissions for patients who underwent total joint arthroplasty (TJA). This study aimed to predict 90-day TJA readmissions from our comprehensive electronic health record data and routinely collected patient-reported outcome measures. Methods: We retrospectively queried all TJA-related readmissions in our tertiary care center between 2016 and 2019. A total of 104-episode care characteristics and preoperative patient-reported outcome measures were used to develop several machine learning models for prediction performance evaluation and comparison. For interpretability, a logistic regression model was built to investigate the statistical significance, magnitudes, and directions of associations between risk factors and readmission. Results: Given the significant imbalanced outcome (5.8% of patients were readmitted), our models robustly predicted the outcome, yielding areas under the receiver operating characteristic curves over 0.8, recalls over 0.5, and precisions over 0.5. In addition, the logistic regression model identified risk factors predicting readmission: diabetes, preadmission medication prescriptions (ie, nonsteroidal anti-inflammatory drug, corticosteroid, and narcotic), discharge to a skilled nursing facility, and postdischarge care behaviors within 90 days. Notably, low self-reported confidence to carry out social activities accurately predicted readmission. Conclusions: A machine learning model can help identify patients who are at substantially increased risk of a readmission after TJA. This finding may allow for health-care providers to increase resources targeting these patients. In addition, a poor response to the "social activities" question may be a useful indicator that predicts a significant increased risk of readmission after TJA.

Physics-informed and simulation-driven optimization for binary Fourier single-pixel imaging.

Binary patterns are used in fast Fourier single-pixel imaging (FSI) technology to increase the imaging speed at the expense of spatial resolution or image quality. In this Letter, we propose a method for optimizing the image quality-speed trade-off that is informed by physical principles and driven by data from simulations. To compensate for the quantization error induced by binary dithering, convolution kernels are proposed and optimized for both low and high spatial frequencies. The proposed method has been demonstrated to work in both simulation and experiments. Other single-pixel imaging (SPI) techniques may also benefit from this approach.

Dual Heterojunction of Etched MIL-68(In)-NH2 Supported Heptazine-/Triazine-Based Carbon Nitride for Improved Visible-Light Nitrogen Reduction.

This work reports a dual heterojunction of etched MIL-68(In)-NH2 (MN) supported heptazine-/triazine-based carbon nitride (HTCN) via a facile hydrothermal process for photocatalytic ammonia (NH3 ) synthesis. By applying the hydrothermal treatment, MN microrods are chemically etched into hollow microtubes, and HTCN with nanorod array structures are simultaneously tightly anchored on the outside surface of the microtubes. With the addition of 9 wt% HTCN, the resulting dual heterojunction presents an enhanced photocatalytic ammonia yield rate of 5.57 mm gcat -1 h-1 with an apparent quantum efficiency of 10.89% at 420 nm. Moreover, stable ammonia generation using seawater, tap water, lake water, and turbid water in the absence of sacrificial reagents verifies the potential of the dual-heterojunction composites as a commercially viable photosystem. The obtained one-dimensional (1D) microtubes and coating of HTCN confers this unique composite with extended visible-light harvesting and accelerated charge carrier migration via a multi-stepwise charge transfer pathway. This work provides a new strategy for optimizing nitrogen (N2 )-into-ammonia conversion efficiency by designing novel dual-heterojunction catalysts.

Association Between High-Level D-Dimer at Admission and Early Intubation in Patients With Moderate Traumatic Brain Injury.

It is unclear who can benefit from tracheal intubation in the moderate (mTBI) traumatic brain injury (TBI) population. Given that mTBI patients are conscious, intubation can cause intense stress, possibly triggering neurological deterioration. Therefore, identifying potential risk factors for intubation in mTBI patients can serve as a valuable clinical warning. We sought to investigate whether elevated D-dimer is a possible risk factor for intubation in mTBI patients. Using the STROBE statement, adult patients with isolated TBI (Glasgow Coma Scale [GCS] score 9-13) treated at a high-volume neurotrauma center between January 2015 and December 2020 were reviewed. The demographics, clinical presentation, neuroimaging, and laboratory information were collected based on the patients' electronic medical record. D-dimer values were assessed from serum when patients were admitted to the hospital. The primary study end-point was that the mTBI patient was intubated within 72 h upon admission. A total of 557 patients with mTBI were finally included in this study. Of these, 85 (15.3%) patients were intubated. Multi-variate logistic regression analysis showed that high-level D-dimer (≥17.9mg/L) was significantly associated with early tracheal intubation in mTBI patients (odds ratio, 3.10 [1.16-8.25]; p = 0.024) after adjusting for age, sex, GCS scores, Marshall scores, and Injury Severity Scores. Sensitivity analysis showed that high-level D-dimer had a robust correlation with intubation in the different subgroups or after propensity score matching. High-level D-dimer on admission is an independent risk factor for early tracheal intubation in isolated mTBI patients.

m6A modification associated with YTHDF1 is involved in Japanese encephalitis virus infection.

N6-methyladenosine (m6A), the most common modification in mammalian mRNA and viral RNA, regulates mRNA structure, stability, translation, and nuclear export. The Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus causing severe neurologic disease in humans. To date, the role of m6A modification in JEV infection remains unclear. Herein, we aimed to determine the impact of m6A methylation modification on JEV replication in vitro and in vivo. Our results demonstrated that the overexpression of the m6A reader protein YTHDF1 in vitro significantly inhibits JEV proliferation. Additionally, YTHDF1 negatively regulates JEV proliferation in YTHDF1 knockdown cells and YTHDF1 knockout mice. MeRIP-seq analysis indicated that YTHDF1 interacts with several interferon-stimulated genes (ISGs), especially in IFIT3. Overall, our data showed that YTHDF1 played a vital role in inhibiting JEV replication. These findings bring novel insights into the specific mechanisms involved in the innate immune response to infection with JEV. They can be used in the development of novel therapeutics for controlling JEV infection.

Dominant mechanism in spinal cord injury-induced immunodeficiency syndrome (SCI-IDS): sympathetic hyperreflexia.

Clinical studies have shown that individuals with spinal cord injury (SCI) are particularly susceptible to infectious diseases, resulting in a syndrome called SCI-induced immunodeficiency syndrome (SCI-IDS), which is the leading cause of death after SCI. It is believed that SCI-IDS is associated with exaggerated activation of sympathetic preganglionic neurons (SPNs). After SCI, disruption of bulbospinal projections from the medulla oblongata C1 neurons to the SPNs results in the loss of sympathetic inhibitory modulation from the brain and brainstem and the occurrence of abnormally high levels of spinal sympathetic reflexes (SSR), named sympathetic hyperreflexia. As the post-injury survival time lengthens, mass recruitment and anomalous sprouting of excitatory interneurons within the spinal cord result in increased SSR excitability, resulting in an excess sympathetic output that disrupts the immune response. Therefore, we first analyze the structural underpinnings of the spinal cord-sympathetic nervous system-immune system after SCI, then demonstrate the progress in highlighting mechanisms of SCI-IDS focusing on norepinephrine (NE)/Beta 2-adrenergic receptor (ß2-AR) signal pathways, and summarize recent preclinical studies examining potential means such as regulating SSR and inhibiting ß2-AR signal pathways to improve immune function after SCI. Finally, we present research perspectives such as to promote the effective regeneration of C1 neurons to rebuild the connection of C1 neurons with SPNs, to regulate excitable or inhibitory interneurons, and specifically to target ß2-AR signal pathways to re-establish neuroimmune balance. These will help us design effective strategies to reverse post-SCI sympathetic hyperreflexia and improve the overall quality of life for individuals with SCI.

Gut microbiota combined with metabolome dissects long-term nanoplastics exposure-induced disturbed spermatogenesis.

As the concerned emerging pollutants, several lines of evidence have indicated that nanoplastics (NPs) lead to reproductive toxicity. However, the biological mechanism underlying NPs disturbed spermatogenesis remains largely unknown. Therefore, we aimed to reveal the potential mechanism of impaired spermatogenesis caused by long-term NPs exposure from the perspective of integrated metabolome and microbiome analysis. After 12 weeks of gavage of polystyrene nanoplastics (PS-NPs) and animo-modified polystyrene nanoplastics (Amino-NPs), a well-designed two-exposure stages experimental condition. We found that NPs exposure induced apparent abnormal spermatogenesis, which appeared more severe in the Amino-NPs group. Mechanistically, 14 floras associated with glucose and lipid metabolism were significantly altered, as evidenced by 16 S rRNA sequencing. Testicular metabolome revealed that the Top 50 changed metabolites were also enriched in lipid metabolism. Subsequently, the combined gut microbiome and metabolome analysis uncovered the strong correlations between Klebsiella, Blautia, Parabacteroides, and lipid metabolites (e.g., PC, LysoPC and GPCho). We speculate that the dysbiosis of gut microbiota-related disturbed lipid metabolism may be responsible for long-term NPs-induced damaged spermatogenesis, which provides new insights into NPs-induced dysregulated spermatogenesis.

Structural characterization and anti-inflammatory effects of Enteromorpha prolifera polysaccharide-Fe/Zn complexes.

The structure of polysaccharide has a great influence on its biological functions, and the chelation with metal ions is an effective way to change polysaccharide structural configuration. Herein, the structure of Enteromorpha prolifera polysaccharide (EP)-Fe/Zn complexes were characterized and the results showed that the iron (III) existed in form of ß-FeOOH in EP-Fe (III) complex and the zinc (II) existed in form of C-O-Zn in EP-Zn (II) complex. Besides, the chelation with iron (III) or zinc (II) completely changed the apparent forms, and improved the thermal stability of EP. Furthermore, the anti-inflammatory activities of EP, EP-Fe and EP-Zn were proved by a lipopolysaccharide (LPS)-induced RAW264.7 macrophages model. The results showed that EP, EP-Fe (III) and EP-Zn (II) could decrease the mitochondrial membrane potential and the secretion of NO and cytokines induced by LPS. One of the anti-inflammatory mechanisms of EP, EP-Fe (III) and EP-Zn (II) was that they could inhibit mitogen-activated protein kinase (MAPK) signaling pathway via increasing its inhibitor content in cells. Collectively, the research suggested that the chelation with iron (III) or zinc (II) could change the structure and improve the anti-inflammatory activities of EP.

Effect of apatinib on the pharmacokinetics of tramadol and O-desmethyltramadol in rats.

Since the combination of anticancer drugs and opioids is very common, apatinib and tramadol are likely to be used in combination clinically. This study evaluated the effects of apatinib on the pharmacokinetics of tramadol and its main metabolite O-desmethyltramadol in Sprague-Dawley (SD) rats and the inhibitory effects of apatinib on tramadol in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP2D6.1. The samples were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vivo results showed that compared with the control group, apatinib increased the AUC(0-t), AUC(0-∞) and Cmax values of tramadol and O-desmethyltramadol, and decreased the values of VZ/F and CLz/F. In addition, the MRT(0-t), MRT(0-∞) values of O-desmethyltramadol were increased. In vitro, apatinib inhibited the metabolism of tramadol by a mixed way with IC50 of 1.927 µM in RLMs, 2.039 µM in HLMs and 15.32 µM in CYP2D6.1. In summary, according to our findings, apatinib has a strong in vitro inhibitory effect on tramadol, and apatinib can increase the analgesic effect of tramadol and O-desmethyltramadol in rats.

Dynamic 3D Measurement without Motion Artifacts Based on Feature Compensation.

Phase-shift profilometry (PSP) holds great promise for high-precision 3D shape measurements. However, in the case of measuring moving objects, as PSP requires multiple images to calculate the phase, the movement of the object causes artifacts in the measurement, which in turn has a significant impact on the accuracy of the 3D surface measurement. Therefore, we propose a method to reduce motion artifacts using feature information in the image and simulate it using the six-step term shift method as a case study. The simulation results show that the phase of the object is greatly affected when the object is in motion and that the phase shift due to motion can be effectively reduced using this method. Finally, artifact optimization was carried out by way of specific copper tube vibration experiments at a measurement frequency of 320 Hz. The experimental results prove that the method is well implemented.

A novel UHPLC‒MS/MS method for quantitative analysis of zanubrutinib in rat plasma: application to an in vivo interaction study between zanubrutinib and triazole antifungal.

BACKGROUND: This study establishes a UHPLC‒MS/MS method for the detection of zanubrutinib and explores its interaction with fluconazole and isavuconazole in rats. METHODS: A protein precipitation method using acetonitrile was used to prepare plasma samples using ibrutinib as an internal standard. Chromatographic separation and mass spectrometric detection of the analytes and internal standards were performed on a Shimadzu 8040 UHPLC‒MS/MS equipped with a Shim-pack velox C18 column (2.1 × 50 mm, 2.7 µm). Methanol and 0.1% formic acid-water were used as mobile phases. Intraday and interday precision and accuracy, extraction recoveries, and matrix effects of this method were determined. The linearity and sample stability of the method were assessed. Eighteen male Sprague‒Dawley (SD) rats were randomly divided into three groups with zanubrutinib (30 mg/kg) alone, zanubrutinib in combination with fluconazole (20 mg/kg) or zanubrutinib in combination with isavuconazole (20 mg/kg). Blood samples (200 µL) were collected at designated time points (ten evenly distributed time points within 12 h). The concentration of zanubrutinib was determined using the UHPLC‒MS/MS method developed in this study. RESULTS: The typical fragment ions were m/z 472.15 → 290.00 for zanubrutinib and m/z 441.20 → 138.10 for ibrutinib (IS). The range of the standard curve was 1-1000 ng/mL with a regressive coefficient (R2) of 0.999. The recoveries and matrix effects were 91.9-98.2% and 97.5-106.3%, respectively, at different concentration levels. The values for intra- and interday RSD% were lower than 9.8% and 5.8%, respectively. The RSD% value was less than 10.3%, and the RE% value was less than ± 4.0% under different storage conditions. Analysis of pharmacokinetic results suggested that coadministration with isavuconazole or fluconazole significantly increased the area under the curve (1081.67 ± 43.81 vs. 1267.55 ± 79.35 vs. 1721.61 ± 219.36), peak plasma concentration (332.00 ± 52.79 vs. 396.05 ± 37.19 vs. 494.51 ± 130.68), and time to peak (1.83 ± 0.41 vs. 2.00 ± 0.00 vs. 2.17 ± 0.41) compared to zanubrutinib alone. CONCLUSION: This study provides information to understand the metabolism of zanubrutinib with concurrent use with isavuconazole or fluconazole, and further clinical trials are needed to validate the results in animals.

Decreased syntaxin17 expression contributes to the pathogenesis of acute pancreatitis in murine models by impairing autophagic degradation.

Acute pancreatitis (AP) is an inflammatory disease of the exocrine pancreas. Disruptions in organelle homeostasis, including macroautophagy/autophagy dysfunction and endoplasmic reticulum (ER) stress, have been implicated in human and rodent pancreatitis. Syntaxin 17 (STX17) belongs to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) subfamily. The Qa-SNARE STX17 is an autophagosomal SNARE protein that interacts with SNAP29 (Qbc-SNARE) and the lysosomal SNARE VAMP8 (R-SNARE) to drive autophagosome-lysosome fusion. In this study, we investigated the role of STX17 in the pathogenesis of AP in male mice or rats induced by repeated intraperitoneal injections of cerulein. We showed that cerulein hyperstimulation induced AP in mouse and rat models, which was characterized by increased serum amylase and lipase activities, pancreatic edema, necrotic cell death and the infiltration of inflammatory cells, as well as markedly decreased pancreatic STX17 expression. A similar reduction in STX17 levels was observed in primary and AR42J pancreatic acinar cells treated with CCK (100 nM) in vitro. By analyzing autophagic flux, we found that the decrease in STX17 blocked autophagosome-lysosome fusion and autophagic degradation, as well as the activation of ER stress. Pancreas-specific STX17 knockdown using adenovirus-shSTX17 further exacerbated pancreatic edema, inflammatory cell infiltration and necrotic cell death after cerulein injection. These data demonstrate a critical role of STX17 in maintaining pancreatic homeostasis and provide new evidence that autophagy serves as a protective mechanism against AP.

Effect of Jin three needles combined with Tong Qiao and blood activation Tang on neurological function, coagulation function and serum level in stroke patients.

To investigate the efficacy and safety of Jin three needles combined with Tong Qiao Wu Blood-streaming Tang in patients with acute ischemic stroke (AIS), this retrospective study analyzed the data of patients with AIS between January 2017 and December 2022. The National Institutes of Health Stroke Scale (NIHSS) scores, blood neuron-specific enolase, S100ß protein (S100ß), fibrinogen (FIB), cerebral infarct volume, D-dimer (D-D), prothrombin time (PT), activated partial thromboplastin time, hypersensitive c-reactive protein (hs-CRP), serum tumor necrosis factor-α (TNF-α), and homocysteine (Hcy) were compared between the 2 groups. The treatment effect was significantly better in the observation group than in the comparison group (P < .05). The NIHSS score, neuron-specific enolase, S100ß, and cerebral infarct volume were significantly lower in both groups after treatment than before treatment (P < .05). FIB and D-D levels were significantly lower and APTT and PT levels were significantly higher in both groups after treatment than before treatment (P < .05). TNF-α, hs-CRP, and Hcy were significantly lower in both groups after treatment than before treatment, and TNF-α, hs-CRP and Hcy were significantly lower in the observation group than in the comparison group (P < .05). No statistically significant difference in the incidence of adverse reactions occurred between the 2 groups (P > .05). Combining Jin three needles can improve the therapeutic effect in patients with AIS, promote the recovery of neurological function, improve coagulation function, and reduce the inflammatory response with good safety.