Phase-Separated Nano-Antibiotics Enhanced Survival in Multidrug-Resistant Escherichia coli Sepsis by Precise Periplasmic EcDsbA Targeting.

Disulfide bond (Dsb) proteins, especially DsbA, represent a promising but as-yet-unrealized target in combating multidrug-resistant (MDR) bacteria because their precise subcellular targeting through multibarrier remains a significant challenge. Here, a novel heterogenization-phase-separated nano-antibiotics (NCefoTs) is proposed, through the co-assembly of enzyme-inhibiting lipopeptides (ELp component), membrane-recognizing and disrupting lipopeptides (MLp component), and cefoperazone. The self-sorting components of MLp "concentrated island-liked clusters" on the surface of NCefoTs promote the efficient penetration of NCefoTs through the outer membrane. Triggered by the DsbA, the precisely spatiotemporal engineered NCefoTs transform to nanofibers in situ and further significantly enhance the inhibition of DsbA. The hydrolytic activity of ß-lactamase and the motility function of flagella are thereby impeded, confirming the efficacy of NCefoTs in restoring susceptibility to antibiotics and inhibiting infection dissemination. By these synergistic effects of NCefoTs, the minimum inhibitory concentration of antibiotics decreases from over 300 µM to 1.56 µM for clinically isolated E. coli MDR. The survival rate of sepsis-inflicted mice is significantly enhanced from 0% to 92% upon encapsulation of cefoperazone in NCefoTs, which rapidly eliminates invading pathogens and mitigates inflammation. The universally applicable delivery system, based on an "on demands" strategy, presents a promising prospect for undruggable antibiotic targets in the periplasm to combat MDR bacteria.

Network pharmacology- and molecular docking-based investigation on the mechanism of action of Si-ni San in the treatment of depression combined with anxiety and experimental verification in adolescent rats.

Background: The incidence rate of adolescent depression and anxiety has been increasing since the outbreak of COVID-19, which there are no effective therapeutic drugs available. Si-ni San is commonly used in traditional Chinese medicine for the treatment of depression-like as well as anxiety-like behavior, but its mechanism for treating depression combined with anxiety during adolescence is not yet clear. Methods: Network pharmacology was used to explore potential drug molecules and related targets, molecular docking and molecular dynamics (MD) simulation were used to evaluate the interaction between the potential drug molecules and related targets, and a model of anxiety combined with depression in adolescent rats as well as the following behavioral tests and molecular biology tests were used to verify the results from network pharmacology and molecular docking. Results: As a result, 256 active ingredients of Si-ni San and 1128 potential targets were screened out. Among them, quercetin, Luteolin, kaempferol, 7-Methoxy-2-methyl isoflavone, formononetin showed to be the most potential ingredients; while STAT3, IL6, TNF, AKT1, AKT1, TP53, IL1B, MAPK3, VEGFA, CASP3, MMP9 showed to be the most potential targets. AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway and TNF signaling pathway, which are involved in anti-inflammation processes, showed to be the most probable pathways regulated by Si-ni San. Molecular docking and MD simulation between the compounds to inflammation-associated targets revealed good binding abilities of quercetin, Luteolin, kaempferol, nobiletin and formononetin to PTGS2 and PPARγ. In the experiment with adolescent rats, Si-ni San markedly suppressed early maternal separation (MS) combined with adolescent chronic unpredictable mild stress (CUMS)-induced depression combined with anxiety. The qPCR results further indicated that Si-ni San regulated the oxidative stress and inflammatory response. Conclusion: This study demonstrates that adolescent anxiety- and depression-like behavior induced by MS combined CUMS can be ameliorated by Si-ni San by improved inflammation in hippocampus via targeting TNF pathway and Nrf2 pathway, helping to reveal the mechanism of Si-ni San in treating adolescent depression combined with anxiety.

SIRT1 Regulates Mitochondrial Damage in N2a Cells Treated with the Prion Protein Fragment 106-126 via PGC-1α-TFAM-Mediated Mitochondrial Biogenesis.

Mitochondrial damage is an early and key marker of neuronal damage in prion diseases. As a process involved in mitochondrial quality control, mitochondrial biogenesis regulates mitochondrial homeostasis in neurons and promotes neuron health by increasing the number of effective mitochondria in the cytoplasm. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates neuronal mitochondrial biogenesis and quality control in neurodegenerative diseases via deacetylation of a variety of substrates. In a cellular model of prion diseases, we found that both SIRT1 protein levels and deacetylase activity decreased, and SIRT1 overexpression and activation significantly ameliorated mitochondrial morphological damage and dysfunction caused by the neurotoxic peptide PrP106-126. Moreover, we found that mitochondrial biogenesis was impaired, and SIRT1 overexpression and activation alleviated PrP106-126-induced impairment of mitochondrial biogenesis in N2a cells. Further studies in PrP106-126-treated N2a cells revealed that SIRT1 regulates mitochondrial biogenesis through the PGC-1α-TFAM pathway. Finally, we showed that resveratrol resolved PrP106-126-induced mitochondrial dysfunction and cell apoptosis by promoting mitochondrial biogenesis through activation of the SIRT1-dependent PGC-1α/TFAM signaling pathway in N2a cells. Taken together, our findings further describe SIRT1 regulation of mitochondrial biogenesis and improve our understanding of mitochondria-related pathogenesis in prion diseases. Our findings support further investigation of SIRT1 as a potential target for therapeutic intervention of prion diseases.

Pediatric oral extemporaneous preparations and practices: International Pharmaceutical Federation (FIP) global study.

This publication is the first to report current, global, pediatric oral extemporaneous compounding practices. Complete survey responses were received from 470 participants actively involved in compounding across all the World Health Organization (WHO) regions. The survey addressed oral formulation of extemporaneous liquids, including the use of commercial or in-house vehicles, flavoring excipients, source of formulation recipes, and beyond use dates (BUDs). Over 90% of the survey participants prepared oral liquids. Solid dosage forms, comprising capsules and powder papers (sachets) were also frequently prepared for children, albeit to a lesser extent. The top 20 active pharmaceutical ingredients compounded for children, globally, were: omeprazole, captopril, spironolactone, propranolol, furosemide, phenobarbital, hydrochlorothiazide, ursodeoxycholic acid, sildenafil, melatonin, clonidine, enalapril, dexamethasone, baclofen, caffeine, chloral hydrate, trimethoprim, atenolol, hydrocortisone, carvedilol and prednisolone. Diuretics, drugs for acid-related disorders, and beta-blockers were the top three most frequently compounded classes per the WHO Anatomical Therapeutic Chemical (ATC) classification system. The principal need identified for the practice of extemporaneous compounding for children was the development of an international, open-access formulary that includes validated formulations, as well as updated compounding literature and guidelines. Furthermore, improved access to data from stability studies to allow compounding of formulations with extended BUDs.

Safety and effectiveness of baloxavir marboxil and oseltamivir for influenza in children: a real-world retrospective study in China.

Objectives: To evaluate the safety and effectiveness of baloxavir marboxil (baloxavir) and oseltamivir in pediatric influenza patients in China. Methods: Patients filling a prescription for baloxavir or oseltamivir within 48 h following an influenza-related outpatient visit were identified in Children's Hospital of Fudan University in China between March 2023 and December 2023. Outcomes were assessed after antiviral treatment and included the incidence of adverse reactions and the duration of fever and other flu symptoms. Results: A total of 1430 patients infected with influenza A were collected and 865 patients (baloxavir: n = 420; oseltamivir: n = 445) finally included. The incidence of adverse reactions of nausea and vomiting was significantly different between the baloxavir group (2.38%) and the oseltamivir group (12.13%) [P < 0.001, OR = 4.2526, 95%CI (2.0549, 9.6080)]. No differences in other adverse reactions were observed between the two groups. The mean duration of fever in baloxavir group (1.43d) was significantly shorter than that in oseltamivir group (2.31d) [P < 0.001, 95%CI (0.7815, 0.9917)]. There were no differences in the mean duration of nasal congestion and runny nose, sore throat, cough, and muscle soreness between two groups. Conclusions: The incidence of nausea and vomiting is lower with baloxavir compared to oseltamivir, and the duration for complete fever reduction is shorter with baloxavir than with oseltamivir. The results indicate that baloxavir is well tolerated and effective in Chinese children.

ABCG2 shields against epilepsy, relieves oxidative stress and apoptosis via inhibiting the ISGylation of STAT1 and mTOR.

The transporter protein ABC subfamily G member 2 (ABCG2) is implicated in epilepsy; however, its specific role remains unclear. In this study, we assessed changes in ABCG2 expression and its role in epilepsy both in vitro and in vivo. We observed an instantaneous increase in ABCG2 expression in epileptic animals and cells. Further, ABCG2 overexpression significantly suppressed the oxidative stress and apoptosis induced by glutamate, kainic acid (KA), and lipopolysaccharide (LPS) in neuronal and microglia cells. Furthermore, inhibiting ABCG2 activity offset this protective effect. ABCG2-deficient mice (ABCG2-/-) showed shorter survival times and decreased survival rates when administered with pentylenetetrazole (PTZ). We also noticed the accumulation of signal transducer and activator of transcription 1 (STAT1) and decreased phosphorylation of mammalian target of rapamycin kinase (mTOR) along with increased ISGylation in ABCG2-/- mice. ABCG2 overexpression directly interacted with STAT1 and mTOR, leading to a decrease in their ISGylation. Our findings indicate the rapid increase in ABCG2 expression acts as a shield in epileptogenesis, indicating ABCG2 may serve as a potential therapeutic target for epilepsy treatment.

Microscopic Mechanism and Percolation Model of Dynamic Deposition of Elemental Sulfur Particles in Acidic Gas Reservoirs.

The dissolution of elemental sulfur in acidic gas leads to its precipitation as gas pressure decreases, thereby causing potential damage to the formation due to the deposition of sulfur particles. Previous sulfur deposition prediction models often relied on the solubility of sulfur in acidic gas and the stress state of sulfur particles to determine the occurrence of deposition, thus establishing predictive models. However, in the presence of complex geological conditions, the multiphase flow through porous media and the adsorption of particles on pore throat walls can also influence sulfur particle deposition to some degree. It is well known that sulfur particle deposition during gas reservoir development exhibits instability, with multiple factors influencing the deposited sulfur particles. Particularly noteworthy is the influence of airflow velocity, which can resuspend sulfur particles that are physically adsorbed on pore throat surfaces, thereby reintegrating them into the gas phase. Additionally, the dynamic deposition of larger sulfur particles involves a dynamic process. This study elucidates the dynamic process of sulfur deposition by considering the diverse transport dynamics of sulfur particles. Physical adsorption and desorption behaviors of sulfur particles are determined based on variations in reservoir conditions. The desorption status of sulfur particles with different particle sizes within the formation is established by evaluating the equilibrium between the force exerted on the pore throat wall and the suspension force generated by gas flow. The critical conditions for sulfur deposition in Yuanba gas reservoir were obtained by substituting on-site parameters into calculations. Moreover, a mathematical model is proposed to describe the dynamic deposition and migration of sulfur particles, adopting principles from continuous porous media porous flow theory, fluid flow mass conservation, as well as sulfur particle desorption and migration. The formulated model is solved, and its resulting solution process and outcomes hold significant implications for numerical simulation and predictive assessment of the development impact on gas reservoirs, particularly in later stages.

Validation of Database Autopsy for Review of Pregnancy-Associated Deaths in Canada.

The database autopsy method was developed to determine probable causes of maternal deaths in the Canadian Institute for Health Information's hospital discharge abstract database; however, the method has yet to be validated. Using immediate cause of death information from Québec's hospitalization database as the gold standard, this study assessed the validity and reliability of the database autopsy method for pregnancy-associated deaths. The method had high sensitivity and specificity for identifying the most common causes of these deaths, as well as high interobserver agreement. We conclude that the database autopsy method is valid and reliable overall.

Inspection of Liner Wall Thinning and Interface Debonding in Bimetallic Lined Pipes Using Pulsed Eddy Current Testing.

Bimetallic lined pipe (BLP) has been increasingly used in offshore and subsea oil and gas structures, but how to identify the invisible inner defects such as liner wall thinning and interface debonding is a challenge for future development. A nondestructive testing (NDT) method based on pulsed eddy current testing (PECT) has been proposed to face these difficulties. The inspection of the BLP specimen (AISI1020 base tube and SS304 liner) is implemented from outside of the pipe by using a transmitter-receiver-type PECT probe consisting of two induction coils. By simplifying the BLP specimen to stratified conductive plates, the electromagnetic field interaction between the PECT probe and specimen is analytically modeled, and the probe inspection signals due to liner wall thinning and interface debonding are calculated. In order to highlight the weak response (in microvolts) from the liner, the inspection signals are subtracted by the signal, which is calculated in the case of only having a base tube, yielding differential PECT signals. The peak voltage of the differential signal is selected to characterize the liner wall thinning and interface debonding due to its distinguishable and linear variation. Experiment verification is also carried out on a double-walled specimen simulated by a combination of a Q235 casing pipe and SS304 tubes of different sizes. The experimental results basically agree with the analytical predictions. The peak value of the PECT signal has an ascending and descending variation with the increase in the remaining liner wall thickness and debonding gap, respectively, while the negative peak value shows opposite changes. The peak value exhibits a larger sensitivity than the negative peak value. The proposed method shows potential promise in practical applications for the evaluation of the inner defects in BLP lines.

ROS-responsive biomimetic nanosystem camouflaged by hybrid membranes of platelet-exosomes engineered with neuronal targeting peptide for TBI therapy.

Recovery and survival following traumatic brain injury (TBI) depends on optimal amelioration of secondary injuries at lesion site. Delivering mitochondria-protecting drugs to neurons may revive damaged neurons at sites secondarily traumatized by TBI. Pioglitazone (PGZ) is a promising candidate for TBI treatment, limited by its low brain accumulation and poor targetability to neurons. Herein, we report a ROS-responsive nanosystem, camouflaged by hybrid membranes of platelets and engineered extracellular vesicles (EVs) (C3-EPm-|TKNPs|), that can be used for targeted delivery of PGZ for TBI therapy. Inspired by intrinsic ability of macrophages for inflammatory chemotaxis, engineered M2-like macrophage-derived EVs were constructed by fusing C3 peptide to EVs membrane integrator protein, Lamp2b, to confer them with ability to target neurons in inflamed lesions. Platelets provided hybridized EPm with capabilities to target hemorrhagic area caused by trauma via surface proteins. Consequently, C3-EPm-|PGZ-TKNPs| were orientedly delivered to neurons located in the traumatized hemisphere after intravenous administration, and triggered the release of PGZ from TKNPs via oxidative stress. The current work demonstrate that C3-EPm-|TKNPs| can effectively deliver PGZ to alleviate mitochondrial damage via mitoNEET for neuroprotection, further reversing behavioral deficits in TBI mice. Our findings provide proof-of-concept evidence of C3-EPm-|TKNPs|-derived nanodrugs as potential clinical approaches against neuroinflammation-related intracranial diseases.

Activation of BK channels prevents diabetes-induced osteopenia by regulating mitochondrial Ca2+ and SLC25A5/ANT2-PINK1-PRKN-mediated mitophagy.

Osteopenia and osteoporosis are among the most common metabolic bone diseases and represent major public health problems, with sufferers having an increased fracture risk. Diabetes is one of the most common diseases contributing to osteopenia and osteoporosis. However, the mechanisms underlying diabetes-induced osteopenia and osteoporosis remain unclear. Bone reconstruction, including bone formation and absorption, is a dynamic process. Large-conductance Ca2+-activated K+ channels (BK channels) regulate the function of bone marrow-derived mesenchymal stem cells, osteoblasts, and osteoclasts. Our previous studies revealed the relationship between BK channels and the function of osteoblasts via various pathways under physiological conditions. In this study, we reported a decrease in the expression of BK channels in mice with diabetes-induced osteopenia. BK deficiency enhanced mitochondrial Ca2+ and activated classical PINK1 (PTEN induced putative kinase 1)-PRKN/Parkin (parkin RBR E3 ubiquitin protein ligase)-dependent mitophagy, whereas the upregulation of BK channels inhibited mitophagy in osteoblasts. Moreover, SLC25A5/ANT2 (solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 5), a critical inner mitochondrial membrane protein participating in PINK1-PRKN-dependent mitophagy, was also regulated by BK channels. Overall, these data identified a novel role of BK channels in regulating mitophagy in osteoblasts, which might be a potential target for diabetes-induced bone diseases.Abbreviations: AGE, advanced glycation end products; Baf A1, bafilomycin A1; BK channels, big-conductance Ca2+-activated K+ channels; BMSCs, bone marrow-derived mesenchymal stem cells; BSA, bovine serum albumin; FBG, fasting blood glucose; IMM, inner mitochondrial membrane; ITPR1, inositol 1,4,5-trisphosphate receptor 1; MAM, mitochondria-associated ER membrane; OMM, outer mitochondrial membrane; PINK1, PTEN induced putative kinase 1; PPID/CyP-D, peptidylprolyl isomerase D (cyclophilin D); PRKN/PARK2, parkin RBR E3 ubiquitin protein ligase; ROS, reactive oxygen species; SLC25A5/ANT2, solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 5; STZ, streptozotocin.

Efficacy and safety of surufatinib plus toripalimab, a chemotherapy-free regimen, in patients with advanced gastric/gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, or biliary tract cancer.

BACKGROUND: The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib showed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumors in a phase I study. METHODS: This open-label, multi-cohort study in China enrolled patients with advanced solid tumors who had failed or were intolerable to standard treatment into tumor-specific cohorts. Patients received surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every three weeks). Results for three cohorts (gastric/gastroesophageal junction [GC/GEJ] adenocarcinoma, esophageal squamous cell carcinoma [ESCC], and biliary tract carcinoma [BTC]) are reported here. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation criteria in Solid Tumors version 1.1. RESULTS: Between December 17, 2019, and January 29, 2021, 60 patients were enrolled (GC/GEJ, n = 20; ESCC, n = 20; BTC, n = 20). At data cutoff (February 28, 2023), ORRs were 31.6%, 30.0%, and 11.1%, respectively. Median progression-free survival was 4.1, 2.7, and 2.9 months, respectively. Median overall survival was 13.7, 10.4, and 7.0 months, respectively. Overall, grade ≥ 3 treatment-related adverse events occurred in 28 (46.7%) patients. CONCLUSIONS: Surufatinib plus toripalimab showed promising antitumor activity and a tolerable safety profile in immunotherapy-naïve patients with GC/GEJ adenocarcinoma, ESCC, or BTC. These findings warrant further study in larger randomized trials comparing surufatinib plus toripalimab with standard therapies in these tumors. CLINICALTRIALS: gov NCT04169672.

A colorimetric and electrochemical dual-mode Hg2+ sensor utilizing oxidase-like activity arising from the combination of Hg2+ and palladium metal-organic framework@graphene.

Developing convenient and reliable methods for Hg2+ monitoring is highly important. Some precious metal nanomaterials with intriguing peroxidase-like activity have been used for highly sensitive Hg2+ detection. However, H2O2 must be added during these detections, which impedes practical applications of Hg2+ sensors due to its susceptible decomposition by environmental factors. Herein, we discovered that the combination of Hg2+ and palladium metal-organic framework@graphene (Pd-MOF@GNs) exhibits oxidase-like activity (OXD). In the absence of H2O2, this activity not only catalyzes the oxidation of chromogenic substrates such as 3,3',5,5'-tetramethylbenzidine (TMB) or o-phenylenediamine (OPD) to produce a color change but also enhances the electrical signals during OPD oxidation. Based on these properties, an effective and convenient dual-mode colorimetric and electrochemical sensor for Hg2+ has been developed. The colorimetric and amperometric linear relationships for Hg2+ were 0.045 µM-0.25 mM and 0.020 µM-2.0 mM, respectively. The proposed strategy shows good recovery in real sample tests, indicating promising prospects for multiple environmental sample detection of Hg2+ without relying on H2O2. The colorimetric and electrochemical dual-mode Hg2+ sensor is expected to hold great potentials in applications such as environmental monitoring, rapid field detection, and integration into smartphone detection of Hg2+.

Quantitative proteomics revealed protein biomarkers to distinguish malignant pleural effusion from benign pleural effusion.

To identify protein biomarkers capable of early prediction regarding the distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients with lung disease. A four-dimensional data independent acquisition (4D-DIA) proteomic was performed to determine the differentially expressed proteins in samples from 20 lung adenocarcinoma MPE and 30 BPE. The significantly differential expressed proteins were selected for Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. Protein biomarkers with high capability to discriminate MPE from BPE patients were identified by Random Forest (RF) algorithm prediction model, whose diagnostic and prognostic efficacy in primary tumors were further explored in public datasets, and were validated by ELISA experiment. 50 important proteins (30 up-regulated and 20 down-regulated) were selected out as potential markers to distinguish the MPE from BPE group. GO analysis revealed that those proteins involving the most important cell component is extracellular space. KEGG analysis identified the involvement of cellular adhesion molecules pathway. Furthermore, the Area Under Curve (AUC) of these proteins were ranged from 0.717 to 1.000，with excellent diagnostic properties to distinguish the MPE. Finally, significant survival and gene and protein expression analysis demonstrated BPIFB1, DPP4, HPRT1 and ABI3BP had high discriminating values. SIGNIFICANCE: We performed a 4D-DIA proteomics to determine the differentially expressed proteins in pleural effusion samples from MPE and BPE. Some potential protein biomarkers were identified to distinguish the MPE from BPE patients., which may provide helpful diagnostic and therapeutic insights for lung cancer. This is significant because the median survival time of patients with MPE is usually 4-12 months, thus, it is particularly important to diagnose MPE early to start treatments promptly. The most common causes of MPE are lung cancers, while pneumonia and tuberculosis are the main causes of BPE. If more diagnostic markers could be identified periodically, there would be an important significance to clinical diagnose and treatment with drugs in lung cancer patients.

In Situ Chemical Modulation of Graphitization Degree of Carbon Fibers and Its Potassium Storage Mechanism.

Graphite is considered to be the most auspicious anode candidate for potassium ion batteries. However, the inferior rate performances and cycling stability restrict its practical applications. Few studies have investigated the modulating the graphitization degree of graphitic materials. Herein, a nitrogen-doped carbon-coated carbon fiber composite with tunable graphitization (CNF@NC) through etching growth, in-situ oxidative polymerization, and subsequent carbonization process is reported. The prepared CNF@NC with abundant electrochemical active sites and a rapid K+/electron transfer pathway, can effectively shorten the K+ transfer distance and promote the rapid insertion/removal of K+. Amorphous domains and short-range curved graphite layers can provide ample mitigation spaces for K+ storage, alleviating the volume expansion of the highly graphitized CNF during repeated K+ insertion/de-intercalation. As expected, the CNF@NC-5 electrode presents a high initial coulombic efficiency (ICE) of 69.3%, an unprecedented reversible volumetric capacity of 510.2 mA h cm-3 at 0.1 A g-1 after 100 cycles with the mass-capacity of 294.9 mA h g-1. The K+ storage mechanism and reaction kinetic analysis are studied by combining in-situ analysis and first-principles calculation. It manifests that the K+ storage mechanism in CNF@NC-5 is an adsorption-insertion-insertion mechanism (i.e., the "1+2" model). The solid electrolyte interphase (SEI) film forming is also detected.

Soil water dynamics and deep percolation in an agricultural experimental area of the North China Plain over the past 50 years: Based on field monitoring and numerical modeling.

The unregulated irrigation systems used in the late 20th century have led to increasingly severe deep percolation (DP) in the agricultural irrigation areas of the North China Plain. This has become an important factor limiting the efficient utilization of water resources and sustainable environmental development in these irrigation areas. However, the thick vadose zone is hydrodynamically exceptionally complex. The soil hydrological cycle is constantly changing under the influence of major climate change and human activity, thereby causing changes in DP that are difficult to quantify accurately. Here, the Luancheng Agricultural Irrigation District in North China was selected for a continuous 20-year in situ experiment. Soil-water dynamics were monitored using neutron probes and tensiometers, to determine the complete annual soil-water cycle and the hydrodynamic properties of the thick vadose zone irrigation district. For 1971-2021, DP was simulated using the HYDRUS-1D model and was verified by fitting observed values. Soil water content (SWC) exhibited similar trends in years that differed in terms of the amounts of irrigation and precipitation. The 0-100 cm soil layer was significantly affected by precipitation and other factors, and recharge >60 mm/d caused percolation. DP occurred mostly after irrigation or during the period of intensive precipitation in July-October. The maximum percolation rate was 16.9 mm/d under the present irrigation method. The main factors leading to DP were soil water storage capacity (R2 = 0.86) and precipitation (R2 = 0.54). Under the evolution of irrigation measures in the last 50 years, the average DP has gradually decreased from 574.2 mm (1971-1990) to 435.5 mm (2005-2021). However, a substantial amount of precipitation and irrigation water infiltrated the soil and percolated into the deep soil layer without being utilized by the crop. Therefore, there is an urgent need to consider measures to reduce DP to improve water-use efficiency in agriculture.

Application of artificial intelligence in the diagnosis, treatment, and recurrence prediction of peritoneal carcinomatosis.

Peritoneal carcinomatosis (PC) is a type of secondary cancer which is not sensitive to conventional intravenous chemotherapy. Treatment strategies for PC are usually palliative rather than curative. Recently, artificial intelligence (AI) has been widely used in the medical field, making the early diagnosis, individualized treatment, and accurate prognostic evaluation of various cancers, including mediastinal malignancies, colorectal cancer, lung cancer more feasible. As a branch of computer science, AI specializes in image recognition, speech recognition, automatic large-scale data extraction and output. AI technologies have also made breakthrough progress in the field of peritoneal carcinomatosis (PC) based on its powerful learning capacity and efficient computational power. AI has been successfully applied in various approaches in PC diagnosis, including imaging, blood tests, proteomics, and pathological diagnosis. Due to the automatic extraction function of the convolutional neural network and the learning model based on machine learning algorithms, AI-assisted diagnosis types are associated with a higher accuracy rate compared to conventional diagnosis methods. In addition, AI is also used in the treatment of peritoneal cancer, including surgical resection, intraperitoneal chemotherapy, systemic chemotherapy, which significantly improves the survival of patients with PC. In particular, the recurrence prediction and emotion evaluation of PC patients are also combined with AI technology, further improving the quality of life of patients. Here we have comprehensively reviewed and summarized the latest developments in the application of AI in PC, helping oncologists to comprehensively diagnose PC and provide more precise treatment strategies for patients with PC.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma

Purpose To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). Method and materials All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8 years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. Results ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5 days, P = 0.042) than in the MF group. Conclusion The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC (AU)