Investigating agricultural water sustainability in arid regions with Bayesian network and water footprint theories.

Water scarcity is a significant constraint in agricultural ecosystems of arid regions, necessitating sustainable development of agricultural water resources. This study innovatively combines Bayesian theory and Water Footprint (WF) to construct a Bayesian Network (BN). Water quantity and quality data were evaluated comprehensively by WF in agricultural production. This evaluation integrates WF and local water resources to establish a sustainability assessment framework. Selected nodes are incorporated into a BN and continuously updated through structural and parameter learning, resulting in a robust model. Results reveal a nearly threefold increase of WF in the arid regions of Northwest China from 1989 to 2019, averaging 189.95 × 108 m3 annually. The region's agricultural scale is expanding, and economic development is rapid, but the unsustainability of agricultural water use is increasing. Blue WF predominates in this region, with cotton having the highest WF among crops. The BN indicates a 70.1 % probability of unsustainable water use. Sensitivity analysis identifies anthropogenic factors as primary drivers influencing water resource sustainability. Scenario analysis underscores the need to reduce WF production and increase agricultural water supply for sustainable development in arid regions. Proposed strategies include improving irrigation methods, implementing integrated water-fertilizer management, and selecting drought-resistant, economically viable crops to optimize crop planting structures and enhance water use efficiency in current agricultural practices in arid regions. This study not only offers insights into water management in arid regions but also provides practical guidance for similar agricultural contexts. The BN model serves as a flexible tool for informed decision-making in dynamic environments.

Relationship between Texture, Hydrogen Content, Residual Stress and Corrosion Resistance of Electrodeposited Chromium Coating: Influence of Heat Treatment.

Electrodeposited chromium plating continues to be widely used in a number of specialized areas, such as weapons, transport, aerospace, etc. However, the formation of texture, hydrogen content and residual stress can degrade the serviceability and lead to material failure. The effect of post heat treatment processes on the relationship of texture, hydrogen content, residual stress and corrosion resistance of hexavalent [Cr(VI)] chromium coatings deposited on Cr-Ni-Mo-V steel substrates was investigated. Macrotexture was measured by XRD. Microtexture, dislocation density and grain size were studied by EBSD. With the increase of the heat treatment temperature, it was found that the fiber texture strength of the (222) plane tended to increase and subsequently decrease. Below 600 °C, the increase in the (222) plane texture carried a decrease in the hydrogen content, residual stress, microhardness and an increase in the corrosion resistance. In addition, crack density and texture strength were less affected by the heat treatment time. Notably, relatively fewer crack densities of 219/cm2, a lower corrosion current density of 1.798 × 10-6 A/dm2 and a higher microhardness of 865 HV were found under the preferred heat treatment temperature and time of 380 °C and 4 h, respectively. The hydrogen content and residual stress were 7.63 ppm and 61 MPa, with 86% and 75% reduction rates compared to the as-plated state, respectively. In conclusion, in our future judgement of the influence of heat treatment on coating properties, we can screen or determine to a certain extent whether the heat treatment process is reasonable or not by measuring only the macrotexture.

Assessing anorectal function in patients with recurrent ulcerative colitis.

PURPOSE: Ulcerative colitis (UC) is an inflammatory bowel disease with an unclear etiology that can lead to irreversible changes in distal colonic function in chronic patients. This study investigated anorectal function in recurrent UC patients and identified influencing factors. METHODS: This prospective study enrolled 33 recurrent UC patients and 40 newly diagnosed patients from January 2019 to December 2022. Data collection included clinical records, scores, and anorectal function assessments. Regression analyses were used to identify factors impacting anorectal function. RESULTS: Recurrent UC patients had higher baseline CRP and fecal calprotectin levels, increased anxiety and depression, and more severe fecal incontinence. They also had lower BMIs, serum Hb and albumin (ALB) levels, and Inflammatory Bowel Disease Questionnaire scores than did initial-onset UC patients. Multivariate linear regression analysis revealed that long disease duration (coef. - 0.376, P < 0.001) and high fecal calprotectin level (coef. - 0.656, P < 0.001) independently influenced the initial sensation threshold in recurrent UC patients. Additionally, high fecal calprotectin (coef. - 0.073, P = 0.013) and high Zung Self-Rating Anxiety Scale score (coef. - 0.489, P = 0.001) were identified as two independent determinants of the defecation volume threshold. For the defecation urgency threshold, the independent factors included high disease duration (coef. - 0.358, P = 0.017) and high fecal calprotectin level (coef. - 0.499, P = 0.001). Similarly, the sole independent factor identified for the maximum capacity threshold was high fecal calprotectin (coef. - 0.691, P = 0.001). CONCLUSION: Recurrent UC patients had increased rectal sensitivity and compromised anorectal function, which significantly impacted quality of life. Proactively managing the disease, reducing UC relapses, and addressing anxiety are effective measures for improving anorectal function in these patients.

Unveiling clinicopathologic features and outcomes for endoscopic submucosal dissection of early gastric cancer at gastric angulus in China.

BACKGROUND: With advances in endoscopic submucosal dissection (ESD) technique, an increasing number of the Chinese population are being diagnosed with early gastric cancers (EGCs) at gastric angulus. However, the relationship between gastric angulus and EGCs remains obscure. OBJECTIVES: We aimed to unveil the unreported location characteristics of gastric angulus in Chinese EGC patients and the correlation between the degree of submucosal fibrosis and ESD outcomes. METHODS: We retrospectively reviewed the medical records of EGC patients treated with ESD from January 2010 to March 2023. We retrospectively investigated and analyzed 740 EGC patients using multiple analyses. RESULTS: Following gastric antrum (53.1%), the gastric angulus (21.8%) emerged as the second-most prevalent site for EGCs. It had highest incidence of severe submucosal fibrosis and ulceration than the other parts. Multivariate analysis showed independent associations of submucosal fibrosis at the angulus with ulceration (OR: 3.714, 95% CI: 1.041-13.249), procedure duration (OR: 1.037, 95% CI: 1.014-1.061), and perforation complication (OR: 14.611, 95% CI: 1.626-131.277) (all P < 0.05). CONCLUSIONS: The gastric angulus demonstrates the highest incidence of severe submucosal fibrosis and ulceration for EGCs identified by ESD. This condition is linked to unfavorable outcomes, typically increased perforation risks and prolonged operation duration. Therefore, meticulous dissection is crucial for patients with EGCs in the gastric angulus.

An evolutionarily conserved AnkyrinG-dependent motif clusters axonal K2P K+ channels.

The evolution of ion channel clustering at nodes of Ranvier enabled the development of complex vertebrate nervous systems. At mammalian nodes, the K+ leak channels TRAAK and TREK-1 underlie membrane repolarization. Despite the molecular similarities between nodes and the axon initial segment (AIS), TRAAK and TREK-1 are reportedly node-specific, suggesting a unique clustering mechanism. However, we show that TRAAK and TREK-1 are enriched at both nodes and AIS through a common mechanism. We identified a motif near the C-terminus of TRAAK that is necessary and sufficient for its clustering. The motif first evolved among cartilaginous fish. Using AnkyrinG (AnkG) conditional knockout mice, CRISPR/Cas9-mediated disruption of AnkG, co-immunoprecipitation, and surface recruitment assays, we show that TRAAK forms a complex with AnkG and that AnkG is necessary for TRAAK's AIS and nodal clustering. In contrast, TREK-1's clustering requires TRAAK. Our results expand the repertoire of AIS and nodal ion channel clustering mechanisms and emphasize AnkG's central role in assembling excitable domains.

Inhibition of Cholesteryl Ester Transfer Protein Contributes to the Protection of Ginsenoside Re Against Isoproterenol-Induced Cardiac Hypertrophy.

Background and objectives Ginsenoside Re (Re), a protopanaxatriol-type saponin extracted from ginseng, is known to have potential cardioprotective effects; however, the mechanisms of Re in improving cardiac hypertrophy have not been fully elucidated. This study aimed to investigate the therapeutic effects and underlying mechanism of Re on isoproterenol (ISO)-induced cardiac hypertrophy in vivo and in vitro. Methods Rats were intraperitoneally injected with ISO 30 mg/kg thrice daily for 14 consecutive days to induce cardiac hypertrophy, and these rats were treated with atorvastatin (ATC, 20 mg/kg) or Re (20 mg/kg or 40 mg/kg) once daily for three days in advance until the end of the experiment. Heart weight index, hematoxylin and eosin staining, and hypertrophy-related fetal gene expression were measured to evaluate the effect of Re on cardiac hypertrophy in vivo. Meanwhile, the rat H9c2 cardiomyocyte hypertrophy model was induced by ISO 10 µM for 24 hours. Cell surface area and hypertrophy-related fetal gene expression were determined to assess the effect of Re on ISO-induced cardiomyocyte hypertrophy in vitro. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in both serum and cardiomyocytes were detected by enzymatic colorimetric assays. Furthermore, we chose cholesteryl ester transfer protein (CETP) as a target to explore the influence of Re on CETP expression in vivo and in vitro through real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay. Results Intraperitoneal administration of ISO into rats resulted in increases in cross-sectional cardiomyocyte area, the ratio of heart weight to body weight, the ratio of left ventricular weight to body weight, and the ratio of right ventricular weight to body weight, as well as reactivation of fetal genes; however, treatment with Re or ATC ameliorated most of these hypertrophic responses. Similarly, Re pronouncedly alleviated ISO-induced cardiomyocyte hypertrophy, as evidenced by a decreased cell surface area and downregulation of fetal genes. Moreover, our in vivo and in vitro data revealed that Re reduced TC, TG, and LDL-C levels, and enhanced HDL-C levels. Re improved cardiac hypertrophy mainly associated with the inhibition of mRNA level and protein expression of CETP, to an extent comparable to that of the classical CETP inhibitor, anacetrapib. Conclusions Our research found that CETP inhibition contributes to the protection of Re against ISO-induced cardiac hypertrophy, which provides evidence for the application of Re for cardiovascular disease treatments.

Berberine ameliorates nonalcoholic fatty liver disease-induced bone loss by inhibiting ferroptosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) may contribute to osteoporosis. Berberine is a traditional Chinese medicine and was recently shown to be beneficial in NAFLD. However, little is known about its impact on bone loss induced by NAFLD. AIM: We aimed to explore the role of berberine in bone loss and determine its underlying mechanisms in NAFLD. METHODS: C57BL/6 mice were fed a high-fat high-fructose high-glucose diet (HFFGD) for 16 weeks to establish a NAFLD mouse model. The mice were administered berberine (300 mg/kg/d) by gavage, and fatty liver levels and bone loss indicators were tested. RESULTS: Berberine significantly improved HFFGD-induced weight gain, hepatic lipid accumulation and increases in serum liver enzymes, thereby alleviating NAFLD. Berberine increased trabecular number (Tb. N), trabecular thickness (Tb. Th), bone volume to tissue volume ratio (BV/TV), and decreased trabecular separation (Tb. Sp) and restored bone loss in NAFLD. Mechanistically, berberine significantly inhibited ferroptosis and 4-hydroxynonenal (4-HNE), prostaglandin-endoperoxide synthase 2 (PTGS2), and transferrin (TF) levels and increased ferritin heavy chain (FTH) levels in the femurs of HFFGD-fed mice. Moreover, berberine also activated the solute carrier family 7 member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) signaling pathway. CONCLUSION: Berberine significantly ameliorates bone loss induced by NAFLD by activating the SLC7A11/GSH/GPX4 signaling pathway and inhibiting ferroptosis. Therefore, berberine may serve as a therapeutic agent for NAFLD-induced bone loss.

Cardioprotective Potential of Cymbopogon citratus Essential Oil against Isoproterenol-induced Cardiomyocyte Hypertrophy: Possible Involvement of NLRP3 Inflammasome and Oxidative Phosphorylation Complex Subunits.

OBJECTIVE: Cymbopogon citratus (DC.) Stapf is a medicinal and edible herb that is widely used for the treatment of gastric, nervous and hypertensive disorders. In this study, we investigated the cardioprotective effects and mechanisms of the essential oil, the main active ingredient of Cymbopogon citratus, on isoproterenol (ISO)-induced cardiomyocyte hypertrophy. METHODS: The compositions of Cymbopogon citratus essential oil (CCEO) were determined by gas chromatography-mass spectrometry. Cardiomyocytes were pretreated with 16.9 µg/L CCEO for 1 h followed by 10 µmol/L ISO for 24 h. Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated. Subsequently, transcriptome sequencing (RNA-seq) and target verification were used to further explore the underlying mechanism. RESULTS: Our results showed that the CCEO mainly included citronellal (45.66%), geraniol (23.32%), and citronellol (10.37%). CCEO inhibited ISO-induced increases in cell surface area and protein content, as well as the upregulation of fetal gene expression. Moreover, CCEO inhibited ISO-induced NLRP3 inflammasome expression, as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3, ASC, CASP1, GSDMD, and IL-1ß, as well as reduced protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 (p20), GSDMD-FL, GSDMD-N, and pro-IL-1ß. The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes. Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1, Sdhd, mt-Cytb, Uqcrq, and mt-Atp6 but had no obvious effects on mt-Col expression. CONCLUSION: CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.

Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG.

The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice. During development, AnkG is also expressed at comparable levels in oligodendrocytes and facilitates the efficient assembly of paranodal junctions. However, the physiological roles of glial AnkG in the mature nervous system, and its contributions to BD-like phenotypes, remain unexplored. Here, we generated oligodendroglia-specific AnkG conditional knockout mice and observed the destabilization of axoglial interactions in aged but not young adult mice. In addition, these mice exhibited profound histological, electrophysiological, and behavioral pathophysiologies. Unbiased translatomic profiling revealed potential compensatory machineries. These results highlight the critical functions of glial AnkG in maintaining proper axoglial interactions throughout aging and suggests a previously unrecognized contribution of oligodendroglial AnkG to neuropsychiatric disorders.

Postsynaptic ß1 spectrin maintains Na+ channels at the neuromuscular junction.

Spectrins function together with actin as obligatory subunits of the submembranous cytoskeleton. Spectrins maintain cell shape, resist mechanical forces, and stabilize ion channel and transporter protein complexes through binding to scaffolding proteins. Recently, pathogenic variants of SPTBN4 (ß4 spectrin) were reported to cause both neuropathy and myopathy. Although the role of ß4 spectrin in neurons is mostly understood, its function in skeletal muscle, another excitable tissue subject to large forces, is unknown. Here, using a muscle specific ß4 spectrin conditional knockout mouse, we show that ß4 spectrin does not contribute to muscle function. In addition, we show ß4 spectrin is not present in muscle, indicating the previously reported myopathy associated with pathogenic SPTBN4 variants is neurogenic in origin. More broadly, we show that α2, ß1 and ß2 spectrins are found in skeletal muscle, with α2 and ß1 spectrins being enriched at the postsynaptic neuromuscular junction (NMJ). Surprisingly, using muscle specific conditional knockout mice, we show that loss of α2 and ß2 spectrins had no effect on muscle health, function or the enrichment of ß1 spectrin at the NMJ. Muscle specific deletion of ß1 spectrin also had no effect on muscle health, but, with increasing age, resulted in the loss of clustered NMJ Na+ channels. Together, our results suggest that muscle ß1 spectrin functions independently of an associated α spectrin to maintain Na+ channel clustering at the postsynaptic NMJ. Furthermore, despite repeated exposure to strong forces and in contrast to neurons, muscles do not require spectrin cytoskeletons to maintain cell shape or integrity. KEY POINTS: The myopathy found in pathogenic human SPTBN4 variants (where SPTBN4 is the gene encoding ß4 spectrin) is neurogenic in origin. ß1 spectrin plays essential roles in maintaining the density of neuromuscular junction Nav1.4 Na+ channels. By contrast to the canonical view of spectrin organization and function, we show that ß1 spectrin can function independently of an associated α spectrin. Despite the large mechanical forces experienced by muscle, we show that spectrins are not required for muscle cell integrity. This is in stark contrast to red blood cells and the axons of neurons.

Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy: A Multicenter Prospective Randomized Controlled Study.

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

Immunoproximity biotinylation reveals the axon initial segment proteome.

The axon initial segment (AIS) is a specialized neuronal compartment required for action potential generation and neuronal polarity. However, understanding the mechanisms regulating AIS structure and function has been hindered by an incomplete knowledge of its molecular composition. Here, using immuno-proximity biotinylation we further define the AIS proteome and its dynamic changes during neuronal maturation. Among the many AIS proteins identified, we show that SCRIB is highly enriched in the AIS both in vitro and in vivo, and exhibits a periodic architecture like the axonal spectrin-based cytoskeleton. We find that ankyrinG interacts with and recruits SCRIB to the AIS. However, loss of SCRIB has no effect on ankyrinG. This powerful and flexible approach further defines the AIS proteome and provides a rich resource to elucidate the mechanisms regulating AIS structure and function.

Clinical outcomes and risk factors of non-curative endoscopic submucosal dissection for early gastric cancer: a retrospective multicenter study in Zhejiang, China.

Background: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) does not always lead to curative resection. Risk factors of lymph node metastasis (LNM)/local cancer residue after non-curative ESD for EGC have not been fully elucidated. We therefore aimed to clarify them and evaluate whether the "eCura system" is reliable for the risk stratification of LNM after non-curative ESD. Methods: We conducted a multicenter retrospective study at seven institutions in Zhejiang, China, on 128 patients who underwent non-curative ESD for EGC. We divided the patients into two groups according to their therapeutic regimen after non-curative ESD. We analyzed the risk factors for LNM, local cancer residue, cancer recurrence, and cancer-specific mortality. Furthermore, we compared the outcomes in each risk category after applying the "eCura system". Results: Among 68 patients undergoing additional surgery, LNM was found in three (4.41%) patients, while local cancer residue was found in eight (11.76%) patients. Multivariate analysis showed that upper third location and deep submucosal invasion were independent risk factors of LNM and local cancer residue. Among 60 patients who underwent simple follow-up, local cancer recurrence was found in four (6.67%) patients and cancer-specific mortality was found in one (1.67%) patient. There were no independent risk factors of cancer recurrence and cancer-specific mortality in our study. During the follow-up period, 5-year overall survival (OS) and disease-free survival (DFS) were 93.8% and 88.9%, respectively. Additionally, LNM and cancer recurrence were significantly associated with the eCura scoring system (p = 0.044 and p = 0.017, respectively), while local cancer residue and cancer-specific mortality were not (p = 0.478 and p = 0.131, respectively). Conclusion: Clinicians should be aware of the risk factors for the prognosis of patients with non-curative ESD to determine subsequent treatment. Through the application of the "eCura system", additional surgery should be performed in patients with intermediate/high risk of LNM.

Large-scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal cross talk.

Recent advances in human blastoids have opened new avenues for modeling early human development and implantation. One limitation of our first protocol for human blastoid generation was relatively low efficiency. We now report an optimized protocol for the efficient generation of large quantities of high-fidelity human blastoids from naive pluripotent stem cells. This enabled proteomics analysis that identified phosphosite-specific signatures potentially involved in the derivation and/or maintenance of the signaling states in human blastoids. Additionally, we uncovered endometrial stromal effects in promoting trophoblast cell survival, proliferation, and syncytialization during co-culture with blastoids and blastocysts. Side-by-side single-cell RNA sequencing revealed similarities and differences in transcriptome profiles between pre-implantation blastoids and blastocysts, as well as post-implantation cultures, and uncovered a population resembling early migratory trophoblasts during co-culture with endometrial stromal cells. Our optimized protocol will facilitate broader use of human blastoids as an accessible, perturbable, scalable, and tractable model for human blastocysts.

Microfluidic pumps for cell sorting.

Microfluidic cell sorting has shown promising advantages over traditional bulky cell sorting equipment and has demonstrated wide-reaching applications in biological research and medical diagnostics. The most important characteristics of a microfluidic cell sorter are its throughput, ease of use, and integration of peripheral equipment onto the chip itself. In this review, we discuss the six most common methods for pumping fluid samples in microfluidic cell sorting devices, present their advantages and drawbacks, and discuss notable examples of their use. Syringe pumps are the most commonly used method for fluid actuation in microfluidic devices because they are easily accessible but they are typically too bulky for portable applications, and they may produce unfavorable flow characteristics. Peristaltic pumps, both on- and off-chip, can produce reversible flow but they suffer from pulsatile flow characteristics, which may not be preferable in many scenarios. Gravity-driven pumping, and similarly hydrostatic pumping, require no energy input but generally produce low throughputs. Centrifugal flow is used to sort cells on the basis of size or density but requires a large external rotor to produce centrifugal force. Electroosmotic pumping is appealing because of its compact size but the high voltages required for fluid flow may be incompatible with live cells. Emerging methods with potential for applications in cell sorting are also discussed. In the future, microfluidic cell sorting methods will trend toward highly integrated systems with high throughputs and low sample volume requirements.

Co-Delivery Nanomicelles for Potentiating TNBC Immunotherapy by Synergetically Reshaping CAFs-Mediated Tumor Stroma and Reprogramming Immunosuppressive Microenvironment.

Purpose: Immune checkpoint inhibitors (ICI) have received the most attention for triple negative breast cancer (TNBC), while the response rate to ICI remains limited due to insufficient T cell infiltration. It is therefore essential that alternative strategies are developed to improve the therapeutic outcomes of ICI in non-responsive TNBC cases. The efficacy of pH-responsive nanomicelles (P/A/B@NM) co-loaded with paclitaxel (PTX), CXCR4 antagonist AMD3100, and PD-1/PD-L1 inhibitor BMS-1 activating the T cell-mediated antitumor immune response were evaluated using a 4T1 antiPD-1-resistance breast tumor model. Methods: In vitro, pH-responsive antitumor effect of P/A/B@NM was investigated by assessing cell viability, migration and invasion. In vivo, the distribution of P/A/B@NM was visualized in 4T1 orthotopic TNBC model using an IVIS spectrum imaging instrument. The efficacy of the co-delivery nanocarriers was evaluated by monitoring mouse survival, tumor growth and metastasis, cancer-associated fibroblasts (CAFs)-mediated tumor stroma and immunosuppressive microenvironment components, and the recruitment and infiltration of CD8+ T cells. Results: The prepared P/A/B@NM in acid microenvironment demonstrates remarkable cytotoxicity against MDA-MB-231 cells, with an IC50 of 105 µg/mL. Additionally, it exhibits substantial inhibition of tumor cell migration and invasion. The P/A/B@NM based on co-delivery nanocarriers efficiently accumulate at the tumor site and release the drugs in a pH-responsive controlled manner. The nanomedicine-PTX, AMD3100, and BMS-1 formulation significantly inhibits tumor growth and lung/liver metastasis by inducing antitumor immune responses via CXCL12/CXCR4 axis blockade, and immunogenic cell death to reprogramme both tumor stroma and immunosuppressive microenvironment. As a result, CD8+ T cell infiltration is triggered into the tumor site, boosting the efficacy of ICI therapy synergistically. Conclusion: These results demonstrate that combination therapy using P/A/B@NM reshapes CAFs-mediated tumor stroma and immunosuppressive microenvironment, which can enhance the infiltration of CD8+ T cells, thereby reactivating anti-tumor immunity for non-responsive TNBC cases.

Transfer RNA-derived small RNAs (tsRNAs) in gastric cancer.

Transfer RNA-derived small RNAs (tsRNAs) are newly discovered noncoding RNAs (ncRNAs). According to the specific cleavage of nucleases at different sites of tRNAs, the produced tsRNAs are divided into tRNA-derived stress-inducible RNAs (tiRNAs) and tRNA-derived fragments (tRFs). tRFs and tiRNAs have essential biological functions, such as mRNA stability regulation, translation regulation and epigenetic regulation, and play significant roles in the occurrence and development of various tumors. Although the roles of tsRNAs in some tumors have been intensively studied, their roles in gastric cancer are still rarely reported. In this review, we focus on recent advances in the generation and classification of tsRNAs, their biological functions, and their roles in gastric cancer. Sixteen articles investigating dysregulated tsRNAs in gastric cancer are summarized. The roles of 17 tsRNAs are summarized, of which 9 were upregulated and 8 were downregulated compared with controls. Aberrant regulation of tsRNAs was closely related to the main clinicopathological factors of gastric cancer, such as lymph node metastasis, Tumor-Node-Metastasis (TNM) stage, tumor size, and vascular invasion. tsRNAs participate in the progression of gastric cancer by regulating the PTEN/PI3K/AKT, MAPK, Wnt, and p53 signaling pathways. The available literature suggests the potential of using tsRNAs as clinical biomarkers for gastric cancer diagnosis and prognosis and as therapeutic targets for gastric cancer treatment.

Endoscopic Screening for Missed Lesions of Synchronous Multiple Early Gastric Cancer during Endoscopic Submucosal Dissection.

Aims: To evaluate the value of endoscopic screening during endoscopic submucosal dissection (ESD) in the detection of synchronous multiple early gastric cancer (SMEGC) and the risk factors for missed diagnosis of SMEGC. Methods: We conducted gastric endoscopic screening during ESD operation in 271 patients with early gastric cancer (EGC) referred for ESD, and endoscopic follow-up within 1 year after the operation. The detection and characteristics of SMEGC were analyzed in three stages: before ESD, during ESD operation, and within 1 year after ESD. Results: SMEGC was detected in 37 of 271 patients (13.6%). Among them, 21 patients with SMEGC (56.8%) were diagnosed before ESD, 9 (24.3%) were diagnosed with SMEGC by endoscopic screening during ESD operation, and 7 (18.9%) were found to have EGC lesions in the stomach during postoperative endoscopic follow-up within 1 year. The preoperative missed detection rate of SMEGC was 43.2%, and the rate of missed detection could be reduced by 24.3% (9/37) with endoscopic screening during ESD operation. Missed SMEGC lesions were more common in flat or depressed type and smaller in size than the lesions found before ESD. The presence of severe atrophic gastritis and age ≥60 years were significantly correlated with SMEGC (P < 0.05), while multivariate analysis showed that age ≥60 years was an independent risk factor (OR = 2.63, P < 0.05) for SMEGC. Conclusions: SMEGC lesions are apt to be missed endoscopically. Special attention should be paid to small, depressed, or flat lesions in detecting SMEGC, especially in elderly patients or (and) patients with severe atrophic gastritis. Endoscopic screening during ESD operation can effectively reduce the missed diagnosis rate of SMEGC.

Early ambulation and postoperative recovery of patients with lung cancer under thoracoscopic surgery-an observational study.

BACKGROUND: Enhanced recovery after surgery guidelines in China recommend early ambulation within 24 h after surgery. The aims of this audit were to investigate the early ambulation of patients with lung cancer under thoracoscopic surgery, and to explore the influence of different ambulation time on postoperative rehabilitation of patients. METHODS: Using observational study method, observe and record of 226 cases under the thoracoscope surgery early ambulation of patients with lung cancer. Data collected included postoperative bowel movements, chest tube extubation time, length of hospital stay, postoperative pain and the incidence of postoperative complications. RESULTS: The time of first ambulation was (34.18 ± 17.18) h, the duration was (8.26 ± 4.62) min, and the distance was (54.94 ± 46.06) m. The time of first postoperative defecation, the time of chest tube extubation and the length of hospital stay were significantly shortened in patients who ambulate within 24 h, and the pain score on the third day after surgery was decreased, and the incidence of postoperative complications was reduced, with statistical significance (P < 0.05). CONCLUSION: Early ambulation within 24 h after thoracoscopic surgery for lung cancer patients can promote the recovery of intestinal function, early removal of chest tube, shorten the length of hospital stay, relieve pain, reduce the incidence of complications, and facilitate the rapid recovery of patients.