Corrigendum to "Atrase A, a P-III class metalloproteinase purified from cobra venom, exhibits potent anticoagulant activity by inhibiting coagulation pathway and activating the fibrinolytic system" [Heliyon Volume 10, Issue 10, 30 May 2024, Article e30969].

[This corrects the article DOI: 10.1016/j.heliyon.2024.e30969.].

Gene editing by SSB/CRISPR-Cas9 ribonucleoprotein in bacteria.

The application of CRISPR-Cas9 ribonucleoprotein (RNP) for gene editing is commonly used in plants and animals, but its application in bacteria has not been reported. In this study, we employed DNA single-strand binding protein (SSB) to construct an SSB/CRISPR-Cas9 RNP-editing system for non-homologous recombination and homologous recombination gene editing of the upp gene in bacteria. The RNP targeting the upp gene, along with SSB, was introduced into the protoplasts of Escherichia coli, Pseudomonas, and Bacillus subtilis. Transformants were obtained on plates containing 5-fluorouracil (5-FU) with gene editing efficiencies (percentage of transformants relative to the number of protoplasts) of 9.75 %, 5.02 %, and 8.37 %, respectively, and sequencing analysis confirmed 100 % non-homologous recombination. When RNP, SSB, and a 100-nucleotide single-stranded oligodeoxynucleotide (ssODN) donor were introduced into the protoplasts of these bacteria, transformants were obtained with editing efficiencies of 45.11 %, 30.13 %, and 27.18 %, respectively, and sequencing confirmed 100 % homologous recombination knockout of the upp gene. Additionally, introducing RNP, SSB, and a 100 base-pair double-stranded oligodeoxynucleotide (dsODN) donor containing a tetracycline resistance gene (tetR-dsODN) resulted in transformants on 5-FU plates with editing efficiencies of 35.94 %, 22.46 %, and 19.08 %, respectively, with sequencing confirming 100 % homologous recombination replacement of the upp gene with tetR. These results demonstrate that the SSB/CRISPR-Cas9 RNP system can efficiently, simply, and rapidly edit bacterial genomes without the need for plasmids. This study is the first to report the use of RNP-based gene editing in bacteria.

CryoTRANS: predicting high-resolution maps of rare conformations from self-supervised trajectories in cryo-EM.

Cryogenic electron microscopy (cryo-EM) has revolutionized structural biology, enabling efficient determination of structures at near-atomic resolutions. However, a common challenge arises from the severe imbalance among various conformations of vitrified particles, leading to low-resolution reconstructions in rare conformations due to a lack of particle images in these quasi-stable states. We introduce CryoTRANS, a method that predicts high-resolution maps of rare conformations by constructing a self-supervised pseudo-trajectory between density maps of varying resolutions. This trajectory is represented by an ordinary differential equation parameterized by a deep neural network, ensuring retention of detailed structures from high-resolution density maps. By leveraging a single high-resolution density map, CryoTRANS significantly improves the reconstruction of rare conformations and has been validated on four real-world datasets: alpha-2-macroglobulin, actin-binding protein complexes, SARS-CoV-2 spike glycoprotein, and the 70S ribosome. CryoTRANS can also predict high-resolution structures in cryogenic electron tomography maps using a high-resolution cryo-EM map.

Production of eicosapentaenoic acid by Vacuoliviride crystalliferum under 20% CO2 conditions.

Utilizing flue gas CO2 to co-produce eicosapentaenoic acid (EPA) with microalgae is considered an ideal approach for combating climate change and reducing cultivation costs. However, microalgal species that can efficiently produce EPA under high-CO2 conditions are scarce. This study identified that the eustigmatophycean strain Vacuoliviride crystalliferum demonstrates rapid growth under 20 % CO2 conditions (0.22 vvm), achieving a biomass concentration and productivity of 3.90 g/L and 229.26 mg/L/d, respectively. The EPA content and EPA productivity were found to be 4.28 % (w/w) and 9.80 mg/L/d, respectively. Additionally, an improved biomass concentration of 3.39 g/L and EPA content and productivity of 4.32 % (w/w) and 11.28 mg/L/d were obtained in a 30 L up-scaled cultivation system. Taken together, these findings suggest that V. crystalliferum is a promising candidate for integrating flue gas sequestration with EPA production.

Overexpression of METTL14 mediates steatohepatitis and insulin resistance in mice.

Background: Lipid accumulation and redox imbalance, resulting from dysregulation of hepatic fatty acids oxidation, contribute to the development of steatohepatitis and insulin resistance. Recently, dysregulated RNA N6-methyladenosine (m6A) methylation modification has been found involving fatty liver. However, the role of methyltransferase-like 14 (METTL14), the core component of m6A methylation, in the development of steatohepatitis is unknown. Herein, we aimed to explore the role of METTL14 on steatohepatitis and insulin resistance in mice with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: The liver tissues of mice and patients with MASLD were collected to detect the expression of METTL14. METTL14 overexpression and METTL14 silence were used to investigate the effect of METTL14 on lipid metabolism disorder in vivo and in vitro. Knockout of METTL14 in primary hepatocytes was used to investigate the role of Sirtuin 1 (SIRT1) on lipid accumulation induced by METTL14. Results: METTL14 was dramatically up-regulated in the livers of db/db mice, high-fat diet (HFD)-fed mice, and patients with MASLD. METTL14 overexpression exacerbated MASLD and promoted lipid metabolism disorder and insulin resistance in mice. Conversely, METTL14 knockout ameliorated lipid deposition and insulin resistance in HFD-fed mice. Furthermore, METTL14 overexpression facilitated lipid accumulation, while METTL14 knockout reduced lipid accumulation in HepG2 cells and primary hepatocytes. In addition, METTL14 lost up-regulated SIRT1 expression in hepatocytes. SIRT1 deficiency abrogated the ameliorating effects of METTL14 downregulation in MASLD mice. Conclusions: These findings suggest that dysfunction of the METTL14-SIRT1 pathway might promote hepatic steatosis and insulin resistance.

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma

Abstract Background Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. Objective This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. Methods The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. Results The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. Study limitations No animal experiments were conducted to further verify the results. Conclusion Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication.

The von Hippel-Lindau tumor suppressor protein (VHL), an E3 ubiquitin ligase, functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors. Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway, although the specific molecular mechanisms remain unclear. Herein, the roles of mandarin fish ( Siniperca chuatsi) VHL ( scVHL) in the NF-κB signaling pathway and mandarin fish ranavirus (MRV) replication were explored. The transcription of scVHL was induced by immune stimulation and MRV infection, indicating a potential role in innate immunity. Dual-luciferase reporter gene assays and reverse transcription quantitative PCR (RT-qPCR) results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway. Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα, scIKKß, scIκBα, or scp65. Co-immunoprecipitation (Co-IP) analysis identified scIκBα as a novel target protein of scVHL. Moreover, scVHL targeted scIκBα to catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway. Following MRV infection, NF-κB signaling remained activated, which, in turn, promoted MRV replication. These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication. This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.

[Nutritional components of 5 potatoes in Anqing City in 2021].

OBJECTIVE: To analyze the nutrient composition and nutritional value evaluation of 5 potatoes in Anqing City. METHODS: According to the requirements of the Technical Manual for Food Composition Monitoring Projects, 5 types of potato samples were collected from Anqing City, Anhui Province. National standard detection method were used to determine the nutritional components such as water, ash, protein, fat, dietary fiber, sugar, minerals, vitamins, and amino acids in the samples. The index of nutritional quality(INQ) method was used to evaluate proteins, vitamins, and minerals, and the amino acid scoring standard mode(FAO/WHO mode) was used to evaluate the nutritional value of amino acids. RESULTS: Among the 5 types of potatoes, purple potato had the highest protein(2.3 g/100 g) and dietary fiber content(3.6 g/100 g). Sweet potato(red) had the highest carotene content(4003 µg/100 g), sweet potato(white) had the highest content of vitamin C(15.4 mg/100 g). Sugar in potatoes mainly existed in three forms: fructose, glucose, and sucrose; Purple potatoes had the highest levels of calcium(47 mg/100 g) and phosphorus(74 mg/100 g), respectively. Potatoes(white) had the highest content of potassium(401 mg/100 g), while sweet potatoes(red) had the highest content of magnesium(31 mg/100 g). Sodium(104.0 mg/100 g), iron(0.9 mg/100 g), copper(0.17 mg/100 g), and manganese(0.40 mg/100 g) had the highest content in sweet potatoes(white). The Na/K ratio range of the 5 potato varieties was 0.003-0.456, and the INQ of phosphorus, potassium, magnesium, copper, and manganese were greater than 1. The detection result of 5 potatoes all contain 18 amino acids, and aspartic acid was the highest. The amino acid score(AAS) was 0.29-1.35, and the ratio coefficient(RC) was 0.47-1.69. CONCLUSION: The 5 types of potatoes are rich in dietary fiber, vitamin C and minerals, and belong to the high potassium and low sodium type of food. Potatoes can meet the daily needs of the human body for phosphorus, potassium, magnesium copper, and manganese elements. Lysine is rich in content and can be used as a nutritional supplement for grains. The AAS score and RC are close to 1, and the AAS evaluation mode is closer to the human amino acid composition mode, which can meet the daily needs of the human body for this essential amino acid.

Electrostatic-Field-Induced Collapse of Nanobubbles in Nanochannels.

The adsorbed nanobubbles inside the nanochannels can cause fluid transport blockages, which will obviously degrade the nanodevice performance and reduce the lifetime. However, due to small-scale effects, the removal of nanobubbles is a huge challenge at the nanoscale. Herein, molecular dynamics simulations are carried out to study the effect of the electrostatic field on underwater nitrogen nanobubbles confined in nanochannels. It is found that the nanobubbles will collapse under an appropriate electrostatic field, thereby unblocking the transport of water in the nanochannels. The formation of ordered water structures induced by electrostatic fields plays an important role in the removal of nanobubbles from the nanochannels. Our findings provide a convenient, controllable, and remote way to address the blockage problem of nanobubbles in nanochannels, which may have potential applications in improving the performance of fuel cells.

Deciphering the impairment of perimenopausal insomnia on visual search from a neurocognitive processing perspective.

STUDY OBJECTIVES: Perimenopausal insomnia (PMI) is associated with observable performance impairments in visual search tasks. This study examines how various cognitive processing stages contribute to search performance delays in PMI compared to healthy controls (HCs). METHODS: We recruited 76 participants diagnosed with PMI and 63 HCs. Event-related potentials (ERPs) were recorded as participants engaged in a visual search task, reporting the orientation of a color popout target within an array of ellipses. We analyzed group differences in behavioral performance and ERP components across cognitive processing stages. RESULTS: Compared to HCs, PMI patients exhibited behavioral response delays, although accuracy was not different between groups. Electrophysiological analyses revealed group differences across several ERP components. Firstly, the N1 component's amplitude increased bilaterally, suggesting enhanced visual sensory processing. Secondly, a slower and smaller N2pc indicated reduced attentional orienting. Thirdly, a decreased SPCN amplitude pointed to deficits in target discrimination. Fourthly, an increased amplitude of the stimulus-locked LRP, with unchanged latency, suggested heightened neural inputs for maintaining motor initiation speed. Fifthly, prolonged response-locked LRP latency indicated slower motor execution. Finally, these changes in ERP components, along with significant correlations between LRP components and insomnia symptoms, suggest potential neural biomarkers for PMI. CONCLUSIONS: Our findings provide high-temporal-resolution insights into the neurocognitive disruptions associated with PMI, highlighting how sleep disturbances affect cognitive processing in visual tasks. These insights enhance our understanding of PMI and contribute to discussions on neural mechanisms driving behavioral performance in various conditions.

A primate-specific endogenous retroviral envelope protein sequesters SFRP2 to regulate human cardiomyocyte development.

Endogenous retroviruses (ERVs) occupy a significant part of the human genome, with some encoding proteins that influence the immune system or regulate cell-cell fusion in early extra-embryonic development. However, whether ERV-derived proteins regulate somatic development is unknown. Here, we report a somatic developmental function for the primate-specific ERVH48-1 (SUPYN/Suppressyn). ERVH48-1 encodes a fragment of a viral envelope that is expressed during early embryonic development. Loss of ERVH48-1 led to impaired mesoderm and cardiomyocyte commitment and diverted cells to an ectoderm-like fate. Mechanistically, ERVH48-1 is localized to sub-cellular membrane compartments through a functional N-terminal signal peptide and binds to the WNT antagonist SFRP2 to promote its polyubiquitination and degradation, thus limiting SFRP2 secretion and blocking repression of WNT/ß-catenin signaling. Knockdown of SFRP2 or expression of a chimeric SFRP2 with the ERVH48-1 signal peptide rescued cardiomyocyte differentiation. This study demonstrates how ERVH48-1 modulates WNT/ß-catenin signaling and cell type commitment in somatic development.

Self-Adhesive and Self-Sustainable Bioelectronic Patch for Physiological Feedback Electronic Modulation of Soft Organs.

Bionic electrical stimulation (Bio-ES) aims to achieve personalized therapy and proprioceptive adaptation by mimicking natural neural signatures of the body, while current Bio-ES devices are reliant on complex sensing and computational simulation systems, thus often limited by the low-fidelity of simulated electrical signals, and failure of interface information interaction due to the mechanical mismatch between soft tissues and rigid electrodes. Here, the study presents a flexible and ultrathin self-sustainable bioelectronic patch (Bio-patch), which can self-adhere to the lesion area of organs and generate bionic electrical signals synchronized vagal nerve envelope in situ to implement Bio-ES. It allows adaptive adjustment of intensity, frequency, and waveform of the Bio-ES to fully meet personalized needs of tissue regeneration based on real-time feedback from the vagal neural controlled organs. With this foundation, the Bio-patch can effectively intervene with excessive fibrosis and microvascular stasis during the natural healing process by regulating the polarization time of macrophages, promoting the reconstruction of the tissue-engineered structure, and accelerating the repair of damaged liver and kidney. This work develops a practical approach to realize biomimetic electronic modulation of the growth and development of soft organs only using a multifunctional Bio-patch, which establishes a new paradigm for precise bioelectronic medicine.

Bile acids attenuate hepatic inflammation during ischemia/reperfusion injury.

Background & Aims: Persistent cholestasis has been associated with poor prognosis after orthotopic liver transplantation. In this study, we aimed to investigate how the accumulation of tauro-beta-muricholic acid (TßMCA), resulting from the reprogramming of bile acid (BA) metabolism during liver ischemia/reperfusion (IR) stress, attenuates liver inflammation. Methods: Ingenuity Pathway Analysis was performed using transcriptome data from a murine hepatic IR model. Three different models of hepatic IR (liver warm IR, bile duct separation-IR, common bile duct ligation-IR) were employed. We generated adeno-associated virus-transfected mice and CD11b-DTR mice to assess the role of BAs in regulating the myeloid S1PR2-GSDMD axis. Hepatic BA levels were analyzed using targeted metabolomics. Finally, the correlation between the reprogramming of BA metabolism and hepatic S1PR2 levels was validated through RNA-seq of human liver transplant biopsies. Results: We found that BA metabolism underwent reprogramming in murine hepatocytes under IR stress, leading to increased synthesis of TßMCA, catalyzed by the enzyme CYP2C70. The levels of hepatic TßMCA were negatively correlated with the severity of hepatic inflammation, as indicated by the serum IL-1ß levels. Inhibition of hepatic CYP2C70 resulted in reduced TßMCA production, which subsequently increased serum IL-1ß levels and exacerbated IR injury. Moreover, our findings suggested that TßMCA could inhibit canonical inflammasome activation in macrophages and attenuate inflammatory responses in a myeloid-specific S1PR2-GSDMD-dependent manner. Additionally, Gly-ßMCA, a derivative of TßMCA, could effectively attenuate inflammatory injury in vivo and inhibit human macrophage pyroptosis in vitro. Conclusions: IR stress orchestrates hepatic BA metabolism to generate TßMCA, which attenuates hepatic inflammatory injury by inhibiting the myeloid S1PR2-GSDMD axis. Bile acids have immunomodulatory functions in liver reperfusion injury that may guide therapeutic strategies. Impact and implications: Our research reveals that liver ischemia-reperfusion stress triggers reprogramming of bile acid metabolism. This functions as an adaptive mechanism to mitigate inflammatory injury by regulating the S1PR2-GSDMD axis, thereby controlling the release of IL-1ß from macrophages. Our results highlight the crucial role of bile acids in regulating hepatocyte-immune cell crosstalk, which demonstrates an immunomodulatory function in liver reperfusion injury that may guide therapeutic strategies targeting bile acids and their receptors.

Sargassum pallidum reduces inflammation to exert antidepressant effect by regulating intestinal microbiome and ERK1/2/P38 signaling pathway.

Immune inflammation is one of the main factors in the pathogenesis of depression. It is an effective and active way to find more safe and effective anti-inflammatory depressant drugs from plant drugs. The purpose of this study is to explore the potential of marine plant Sargassum pallidum (Turn).C.Ag. (Haihaozi, HHZ) in the prevention and treatment of depression and to explain the related mechanism. Phytochemical analysis showed that alkaloids, terpenes, and organic acids are the main constituents. In vitro and in vivo activity studies showed the anti-neuroinflammatory and antidepressant effect of Sargassum pallidum, furthermore, confirmed that 7-Hydroxycoumarin, Scoparone, and Kaurenoic Acid are important plant metabolites in Sargasum pallidum for anti-neuroinflammation. Mechanism exploration showed that inhibition of ERK1/2/p38 inflammatory signaling pathway contributing to the antidepressant effect of Sargassum pallidum in reducing intestinal inflammatory levels. This study confirmed the value of Sargassum pallidum and its rich plant metabolites in anti-inflammatory depression, providing a new choice for the follow-up research and development of antidepressant drugs.

A diagnostic model for differentiating tuberculous spondylodiscitis from pyogenic spondylodiscitis based on pathogen-confirmed patients.

OBJECTIVE: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. METHODS: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. RESULTS: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability. CONCLUSIONS: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS.

M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db mice.

Objectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism.Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macrophages in alleviating the infammation of DN and explored the mechanism.Results: M2 macrophages hindered the progression of DN, reduced the levels of IL-1ß (DN group was 34%, M2 group was 13%, p < 0.01) and MCP-1 (DN group was 49%, M2 group was 16%, p < 0.01) in the glomeruli. It was also proven that M2 macrophages alleviate mesangial cell injury caused by a high glucose environment. M2 macrophage tracking showed that the infused M2 macrophages migrated to the kidney, and the number of M2 macrophages in the kidney reached a maximum on day 3. Moreover, the ratio of M2 to M1 macrophages was 2.3 in the M2 infusion group, while 0.4 in the DN group (p < 0.01). Mechanistically, M2 macrophages downregulated Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 in mesangial cells.Conclusions: Multiple infusions of M2 macrophages significantly alleviated inflammation in the kidney and hindered the progression of DN at least partially by abrogating the M1/M2 homeostasis disturbances and suppressing the JAK2/STAT3 pathway in glomerular mesangial cells. M2 macrophage infusion may be a new therapeutic strategy for DN treatment.

A LASSO Cox Regression Predictive Model for Patients Undergoing Surgery for Pancreatic Body and Tail Adenocarcinoma Patients: Comparative Long-Term Survival Analysis of Radical Antegrade Modular Pancreatosplenectomy (RAMPS) and Standard Retrograde Pancreatosplenectomy (SPRS).

PURPOSE: This study was designed to assess the advantages of radical antegrade modular pancreatosplenectomy (RAMPS) over standard retrograde pancreatosplenectomy (SPRS) in terms of disease-free survival (DFS) by comparing clinical outcomes. METHODS: Clinical data from 154 patients who underwent distal pancreatectomy at Tianjin Medical University Cancer Institute and Hospital between January 2015 and August 2018 were collected. We compared the preoperative conditions, postoperative complications, and survival outcomes of patients who underwent two different surgical procedures. By creating a LASSO-Cox model, we determined the parameters affecting DFS and the risk ratios of the two surgical procedures on DFS. RESULTS: The R0 resection rate (85.23% vs. 68.18%, P = 0.003), negative posterior margin rate (96.59% vs. 75.76%, P < 0.001), and tumor bed recurrence rate (15.29% vs. 40.00%, P = 0.001) significantly differed between the RAMPS and SPRS groups. The 1-, 3-, and 5-year survival and DFS rates of the RAMPS group were significantly better than those of the SPRS group (P < 0.05). Disease-free survival analysis based on Kaplan-Meier curves revealed that RAMPS was superior to SPRS (P < 0.001). CONCLUSIONS: We recommend RAMPS as the preferred procedure for treating ductal adenocarcinoma of the pancreatic body and tail due to its enhanced lymph node repair capacity and visualization of posterior pancreatic sections, which can increase DFS in patients.

PPM1G promotes autophagy and progression of pancreatic cancer via upregulating HMGB1.

Pancreatic cancer remains one of the most aggressive and lethal malignancies worldwide, with a dismal 5-year relative survival rates of only 12%. Therefore, it is urgent to discover the key molecular markers to improve the therapeutic outcomes in pancreatic cancer. Herein, we first demonstrated that PPM1G is upregulated in pancreatic cancer and that PPM1G depletion decreases pancreatic cancer cell growth in vitro and in vivo. High PPM1G expression was linked to short overall survival of pancreatic cancer patients, which was further validated in the TCGA database. Moreover, by detecting Beclin 1, LC3-II, and SQSTM1/p62 expressions and observing autolysosome under transmission electron microscope, we discovered that PPM1G is a novel positive regulator of macroautophagy/autophagy. Furthermore, by using immunoprecipitation-mass spectrometry (IP-MS) analysis and following systemic molecular biology experiment, we demonstrated PPM1G promotes the autophagy and proliferation of pancreatic cancer by directly upregulating HMGB1. Additionally, patients with both high PPM1G and high HMGB1 exhibited poorer prognosis in our cohort. This study preliminarily investigated the possibility of PPM1G as a potential therapeutic target and prognostic biomarker in pancreatic cancer patients.

Composition Modulation-Mediated Band Alignment Engineering from Type I to Type III in 2D vdW Heterostructures.

Band alignment engineering is crucial for facilitating charge separation and transfer in optoelectronic devices, which ultimately dictates the behavior of Van der Waals heterostructures (vdWH)-based photodetectors and light emitting diode (LEDs). However, the impact of the band offset in vdWHs on important figures of merit in optoelectronic devices has not yet been systematically analyzed. Herein, the regulation of band alignment in WSe2/Bi2Te3- xSex vdWHs (0 ≤ x ≤ 3) is demonstrated through the implementation of chemical vapor deposition (CVD). A combination of experimental and theoretical results proved that the synthesized vdWHs can be gradually tuned from Type I (WSe2/Bi2Te3) to Type III (WSe2/Bi2Se3). As the band alignment changes from Type I to Type III, a remarkable responsivity of 58.12 A W-1 and detectivity of 2.91×1012 Jones (in Type I) decrease in the vdWHs-based photodetector, and the ultrafast photoresponse time is 3.2 µs (in Type III). Additionally, Type III vdWH-based LEDs exhibit the highest luminance and electroluminescence (EL) external quantum efficiencies (EQE) among p-n diodes based on Transition Metal Dichalcogenides (TMDs) at room temperature, which is attributed to band alignment-induced distinct interfacial charge injection. This work serves as a valuable reference for the application and expansion of fundamental band alignment principles in the design and fabrication of future optoelectronic devices.

Exploring Causal Links Between Gut Microbiota and Geriatric Syndromes: A Two-Sample Mendelian Randomization Analysis.

Background: Both observational studies and clinical trials have demonstrated a link between the gut microbiota and the geriatric syndrome. Nevertheless, the exact nature of this relationship, particularly concerning causality, remains elusive. Mendelian randomization (MR) is a method of inference based on genetic variation to assess the causal relationship between an exposure and an outcome. In this study, we conducted a two-sample Mendelian randomization (TSMR) study to fully reveal the potential genetic causal effects of gut microbiota on geriatric syndromes. Methods: This study used data from genome wide association studies (GWAS) to investigate causal relationships between the gut microbiota and geriatric syndromes, including frailty, Parkinson's disease (PD), delirium, insomnia, and depression. The primary causal relationships were evaluated using the inverse-variance weighted method, MR Egger, simple mode, weighted mode and weighted median. To assess the robustness of the results, horizontal pleiotropy was examined through MR-Egger intercept and MR-presso methods. Heterogeneity was assessed using Cochran's Q test, and sensitivity was evaluated via the leave-one-out method. Results: We identified 41 probable causal relationships between gut microbiota and five geriatric syndrome-associated illnesses using the inverse-variance weighted method. Frailty showed five positive and two negative causal relationships, while PD revealed three positive and four negative causal connections. Delirium showed three positive and two negative causal relationships. Similarly, insomnia demonstrated nine positive and two negative causal connections, while depression presented nine positive and two negative causal relationships. Conclusions: Using the TSMR method and data from the public GWAS database and, we observed associations between specific microbiota groups and geriatric syndromes. These findings suggest a potential role of gut microbiota in the development of geriatric syndromes, providing valuable insights for further research into the causal relationship between gut microbiota and these syndromes.