Vacancy Engineering in 2D Transition Metal Chalcogenide Photocatalyst: Structure Modulation, Function and Synergy Application.

Transition metal chalcogenides (TMCs) are widely used in photocatalytic fields such as hydrogen evolution, nitrogen fixation, and pollutant degradation due to their suitable bandgaps, tunable electronic and optical properties, and strong reducing ability. The unique 2D malleability structure provides a pre-designed platform for customizable structures. The introduction of vacancy engineering makes up for the shortcomings of photocorrosion and limited light response and provides the greatest support for TMCs in terms of kinetics and thermodynamics in photocatalysis. This work reviews the effect of vacancy engineering on photocatalytic performance based on 2D semiconductor TMCs. The characteristics of vacancy introduction strategies are summarized, and the development of photocatalysis of vacancy engineering TMCs materials in energy conversion, degradation, and biological applications is reviewed. The contribution of vacancies in the optical range and charge transfer kinetics is also discussed from the perspective of structure manipulation. Vacancy engineering not only controls and optimizes the structure of the TMCs, but also improves the optical properties, charge transfer, and surface properties. The synergies between TMCs vacancy engineering and atomic doping, other vacancies, and heterojunction composite techniques are discussed in detail, followed by a summary of current trends and potential for expansion.

Neoadjuvant Chemotherapy or Adjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Chemotherapy and chemoradiation have become essential adjuncts to improve the survival of patients with resectable esophageal squamous cell carcinoma (ESCC) in the perioperative period. Although preoperative treatment plus surgery is commonly used, controversy remains regarding the optimal treatment strategy for patients with locally advanced ESCC. METHODS: A retrospective review of clinical stage II and III ESCC patients who underwent esophagectomy at Henan Cancer Hospital between October 2014 and October 2017 was performed. The patients were divided into a neoadjuvant chemotherapy (NAC) group and an adjuvant chemotherapy (AC) group. Propensity score matching (PSM) was used to exclude confounders. Survival was estimated using Kaplan‒Meier analysis and compared by the log-rank test. The Cox proportional hazards regression model was used for both the univariate and multivariate analyses. RESULTS: A total of 684 patients were enrolled, including 365 (53.4%) patients in the NAC group. After PSM, 294 pairs of patients were left. NAC prolonged the OS (not reached versus 57.3 months, P = 0.002) and DFS (57.2 vs. 36.4 months, P = 0.010) and decreased the total rate of recurrence (50.1% vs. 59.2%, P = 0.025) and local recurrence (27.9% vs. 36.7%, P = 0.022) compared with AC. The multivariable analyses showed that NAC plus surgery modality was an independent predictor for improved OS (HR: 0.582, 95% CI: 0.467-0.786, P = 0.001). CONCLUSION: NAC plus surgery prolonged OS and DFS, and significantly decreased the total rate of recurrence compared with surgery plus AC in patients with clinical stage II and III ESCC.

Modified peroral endoscopic myotomy technique with retrograde on-demand myotomy for achalasia: a retrospective cohort study (with video).

BACKGROUND: Although myotomy is crucial in peroral endoscopic myotomy (POEM) surgeries, its optimum length remains controversial. Herein, we propose a modified POEM with new method of tailoring myotomy length aim to evaluate the safety, efficacy, and clinical outcomes of this modified POEM compared with standard POEM in type I or II achalasia. METHODS: Seventy-five patients with type I or II achalasia who underwent POEM at the First Hospital of Jilin University between January 2018 and December 2022 were retrospectively analyzed. According to the myotomy approach, these patients were divided into the retrograde on-demand myotomy (RDM, n = 34), with myotomy beginning on gastric side and length tailored by determining the degree of lower esophageal sphincter (LES) distention, and standard myotomy (SM, n = 41) groups. The baseline data, myotomy length, operation time, clinical success rate, adverse event rate, and reflux-related adverse events were compared and analyzed. RESULTS: The median myotomy length in the RDM group was significantly shorter than that in the SM group (6 vs. 8 cm, respectively; p < 0.001). Moreover, the median myotomy time in the RDM group was significantly shorter than that in the SM group (10 vs. 16 min, respectively; p < 0.001). POEM was successfully performed in all the patients. At the 2-year follow-up, high clinical success rates were observed in both the RDM and SM groups (92.0% vs. 93.3%, respectively; p = 1.000). The incidence of intraoperative adverse events and postoperative reflux-related adverse events was low and comparable in both groups. CONCLUSIONS: RDM POEM is a safe and effective method for patients with type I or II achalasia. Furthermore, it has a shorter myotomy length and operation time than standard POEM technique.

Steering the course of CAR T cell therapy with lipid nanoparticles.

Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, and improved safety. Promising preclinical results signal a shift toward safer and more effective CAR T cell treatments. Ongoing research aims to validate these findings in clinical trials, marking a new era guided by LNPs utility in CAR therapy. Herein, we explore the preference for LNPs over traditional methods, highlighting the versatility of LNPs and their effective delivery of nucleic acids. Additionally, we address key challenges in clinical considerations, heralding a new era in CAR T cell therapy.

The prognostic impact of tumor length on pathological stage IA-IC esophageal adenocarcinoma.

This study was completed to evaluate the relationship between tumor length and the prognosis of patients with pathological stage IA-IC esophageal adenocarcinoma (EAC). Patients were identified from the Surveillance, Epidemiology, and End Results Program database (United States, 2006-2015). X-tile software and ROC analysis were mainly used to explore the best threshold of tumor length for dividing patients into different groups, and then propensity score matching (PSM) was used to balance other variables between groups. The primary outcome assessed was overall survival (OS). A total of 762 patients were identified, and 500 patients were left after PSM. Twenty millimeters were used as the threshold of tumor length. Patients with longer tumor lengths showed worse OS (median: 93 vs. 128 months; P = 0.006). Multivariable Cox regression analysis showed that longer tumor length was an independent risk factor (hazard ratio 1.512, 95% confidence interval, 1.158-1.974, P = 0.002). Tumor length has an impact on patients with pathological stage IA-IC EAC who undergo surgery alone. The prognostic value of the pathological stage group may be improved after combining it with tumor length and age.

Unlocking epigenetics for precision treatment of Ewing's sarcoma.

Ewing's sarcoma (EWS) is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults. Despite the efficacy of chemoradiotherapy in some cases, the cure rate for patients with metastatic and recurrent disease remains low. Therefore, there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment. Epigenetic regulation, a crucial factor in physiological processes, plays a significant role in controlling cell proliferation, maintaining gene integrity, and regulating transcription. Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS. A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development. This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS, integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

Breaking down barriers: The potential of smarter CAR-engineered NK cells against solid tumors.

Natural killer (NK) cells are considered to be the foremost fighters of our innate immune system against foreign invaders and thus tend to promptly latch onto the virus-infected and tumor/cancerous cells, killing them through phagocytosis. At present, the application of genetically engineered Chimeric antigen receptor (CAR) receptors ensures a guaranteed optimistic response with NK cells and would not allow the affected cells to dodge or escape unchecked. Hence the specificity and uniqueness of CAR-NK cells over CAR-T therapy make them a better immunotherapeutic choice to reduce the load of trafficking of numerous tumor cells near the healthy cell populations in a more intact way than offered by CAR-T immunotherapy. Our review mainly focuses on the preclinical, clinical, and recent advances in clinical research trials and further strategies to achieve an augmented and efficient cure against solid tumors.

The Feasibility of Early Oral Feeding After Neoadjuvant Chemotherapy Combined With "Non-Tube No Fasting"-Enhanced Recovery.

BACKGROUND: This study aimed to investigate the feasibility of early oral feeding (EOF) after neoadjuvant chemotherapy (nCT) combined with "non-tube no fasting"-enhanced recovery after minimally invasive esophagectomy (MIE). METHODS: This retrospective study investigated patients who underwent nCT combined with non-tube no fasting-enhanced recovery after MIE in the Department of Thoracic Surgery, Ward I, of the authors' hospital from January 2014 to August 2017. These patients were divided into an early oral feeding (EOF) group (n = 112) and a late oral feeding (LOF) group (n = 69). The postoperative complications were compared between the two groups. RESULTS: The study enrolled 181 patients (112 patients in the EOF group and 69 patients in the LOF group). No significant differences were found between the two groups in the incidence rates of complications such as anastomotic leakage (P = 0.961), pneumonia (P = 0.450), respiratory failure (P = 0.944), heart failure (P = 1.000), acute respiratory distress syndrome (ARDS) (P = 0.856), and unplanned reoperation (P = 0.440), whereas the time to the first postoperative flatus/bowel movement (P < 0.001) and the postoperative length of stay (P < 0.001) were significantly better in the EOF group than in the LOF group.. CONCLUSIONS: In this study, EOF after nCT combined with non-tube no fasting-enhanced recovery after MIE did not significantly increase complications, but significantly shortened the time to the first postoperative flatus/bowel movement and the postoperative length of stay.

Patterns and Influence of Lymph Nodal Metastases After Neoadjuvant Chemotherapy and Surgery for Thoracic Esophageal Squamous Cell Carcinoma.

PURPOSE: The purpose of this retrospective study was to define the pattern of lymph nodal metastases in patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemotherapy (NCT) followed by esophagectomy and to evaluate its influence on prognosis. METHODS: A total of 398 patients with clinical stage T3N0 or T1-3N+ ESCC who underwent NCT and radical esophagectomy with two-field lymphadenectomy were included. The distribution and frequency of metastases were counted separately for each lymph node station. The ypN stage, number of positive lymph node stations and lymph node stations with a metastasis rate greater than 5% were analyzed by using univariate Cox regression, followed by separate multivariable Cox regression analyses after adjusting for various clinical factors. RESULTS: Lymph node metastases were most frequently observed in the right upper paratracheal (16.8%) and left gastric artery (13.1%) stations. Multivariable models controlling for clinical factors showed that ypN stage remained a significant independent predictor of survival (N1 vs. N0: hazard ratio [HR], 2.30, 95% confidence interval [CI] 1.38-3.83, P < 0.001; N2 vs. N0: HR, 3.76, 95% CI 2.21-6.38, P < 0.001; N3 vs. N0: HR, 7.14, 95% CI 3.78-13.48, P < 0.001). The model from the multivariable analysis with the highest c-index score, indicating superior discriminatory preference, was ypN stage (c-index, 0.72). CONCLUSIONS: The pattern and influence of lymph node metastases after NCT will provide guidance on the extent of lymphadenectomy. Common positive lymph node stations for thoracic ESCC after NCT include the paratracheal, subcarinal, paraesophageal, paracardial, and left gastric artery stations.

ICSI: an improved contrast source inversion method for electromagnetic inverse scattering problems.

An improved contrast source inversion method (ICSI) is proposed to solve the problem of electromagnetic inverse scattering. Specifically, we first resort Fourier bases to represent contrast source, so that we can solve contrast source in the frequency domain, which can accelerate the solution of contrast source. Then, a spatial-frequency domain constraint is designed to ensure that the spanned-domain calculation is synchronous optimal. Afterwards, a multi-round optimization combined with SVD (the singular value decomposition) is developed to alleviate the reliance on initial guesses. Finally, we utilize a frequency-domain filter to eliminate redundant inversion information and narrow the search scope of the solution. Extensive experiments on the synthetic and real data show that ICSI holds a faster computing speed, a better inversion ability of relative permittivities, and a stronger anti-noise ability.

Smart Copolymer Surface Derived from Geminized Cationic Amphiphilic Polymers for Reversibly Switchable Bactericidal and Self-Cleaning Abilities.

Bacterial adhesion and colonization on material surfaces pose a serious problem for healthcare-associated devices. Cationic amphiphilic polymer brushes are usually used as surface coatings in antibacterial materials to endow an interface with excellent bactericidal efficiency, but they are easily contaminated, which puts a great limitation on their application. Herein, novel antibacterial copolymer brush surfaces containing geminized cationic amphiphilic polymers (pAGC8) and thermoresponsive poly(N-isopropylacrylamide) polymers (pNIPAm) have been synthesized. Surface functionalization of polymer brushes was investigated by X-ray photoelectron spectroscopy, spectroscopic ellipsometry, atomic force microscopy, and water contact angle measurements. A proportion of AGC8 and NIPAm units in copolymer brushes has been adjusted to obtain a high-efficiency bactericidal surface with minimal interference to its self-cleaning property. The killing and releasing efficiency of the optimized surface simultaneously reached up to above 80% for both Staphylococcus aureus and Escherichia coli bacteria, and the bactericidal and self-cleaning abilities are still excellent even after three kill-release cycles. Such a novel copolymer brush system provides innovative guidance for the development of high-efficiency antibacterial materials in biomedical application.

A multicenter randomized, controlled clinical trial of adjuvant sintilimab for esophageal squamous cell carcinoma.

No adjuvant treatment has been established for patients who remain at high risk of recurrence and incidental pathologic lymph node metastasis for esophageal squamous cell carcinoma (ESCC). In this open-label, multicenter, phase III, randomized controlled trial, ESCC patients who did not achieve pathologic complete response after neoadjuvant chemotherapy plus surgery and clinical T1-2 N0 patients with incidental pathologic lymph node metastasis following initial surgery were randomized at a 2:1 ratio to receive either a sintilimab regimen or observational management (NCT05495152). The primary end point was disease-free survival for all randomized patients. The results of this randomized controlled trial addressed controversy regarding the survival benefits of adjuvant sintilimab treatment for patients with resected locally advanced ESCC. Clinical Trial Registration: NCT05495152 (ClinicalTrials.gov).

Gastric defect closure after endoscopic full-thickness resection: the closing while dissecting technique.

BACKGROUND: Complete closure of gastric wall defects is critical following endoscopic full-thickness resection (EFTR). The aim of this study was to evaluate the efficacy, safety, and clinical outcome of a new endoscopic method: closing while dissecting. METHODS: Twenty-seven patients who underwent EFTR were retrospectively analyzed between January 2020 and March 2021. Gastric defects resulting from EFTR were closed using the "interrupted-close during dissection" technique with endoclips. Tumor characteristics, en bloc resection rates, and postoperative adverse events were evaluated. RESULTS: All submucosal tumors were successfully resected and complete resection was histologically confirmed. The mean maximal tumor diameter was 1.3 cm (ranging from 0.8 to 3.0 cm). The majority of these tumors were gastrointestinal stromal tumors (n = 20), Leiomyoma (n = 3), schwannomas (n = 2), others included fibroma (n = 1) and neurogenic tumor (n = 1). There were no cases of hemorrhage, peritonitis, or delayed perforation. Four patients complained of slight abdominal pain, but no hyperpyrexia or serious elevated white blood cell count was detected in the first 24 h after treatment. All wounds were healed on follow-up endoscopy 3 months after the procedure. The mean follow-up duration was 8.5 months (ranging from 3 to 17) and no tumor recurrences were observed. CONCLUSIONS: The feasibility and safety of this interrupted-close during dissection approach allows for clinical applications in EFTR of gastric submucosal tumors.

Probing mutation-induced conformational transformation of the GTP/M-RAS complex through Gaussian accelerated molecular dynamics simulations.

Mutations highly affect the structural flexibility of two switch domains in M-RAS considered an important target of anticancer drug design. Gaussian accelerated molecular dynamics (GaMD) simulations were applied to probe the effect of mutations P40D, D41E, and P40D/D41E/L51R on the conformational transition of the switch domains from the GTP-bound M-RAS. The analyses of free energy landscapes (FELs) not only reveal that three mutations induce less energetic states than the wild-type (WT) M-RAS but also verify that the switch domains are extremely disordered. Principal component analysis (PCA) and dynamics analysis suggest that three mutations greatly affect collective motions and structural flexibility of the switch domains that mostly overlap with binding regions of M-RAS to its effectors, which in turn disturbs the activity of M-RAS. The analyses of the interaction network between GTP and M-RAS show that the high instability in hydrogen bonding interactions (HBIs) of GTP with residue 41 and Y42 in the switch domain I drives the disordered states of the switch domains. This work is expected to provide a molecular mechanism for deeply understanding the function of M-RAS and future drug design towards the treatment of cancers.

Stratification of lymph node metastasis improves diagnostic efficiency in thoracic esophageal squamous cell carcinoma.

INTRODUCTION: Difference of the short diameter of lymph nodes in the main regions of esophageal squamous cell carcinoma (ESCC) and its value in the diagnosis of lymph nodes need to explore. METHODS: The clinical data of patients with thoracic ESCC who underwent surgical treatment in our hospital were collected. The short diameters of the largest lymph node in each region of the patient were measured by preoperative enhanced computed tomography (CT) and were compared with the postoperative pathology. RESULTS: A total of 477 patients with thoracic ESCC who did not receive neoadjuvant therapy were enrolled in this study. The receiver operating characteristic curve suggested that the short diameters of the paracardial nodes, the left gastric nodes, the right recurrent laryngeal nerve nodes, and the left recurrent laryngeal nerve nodes could well predict the postoperative pathology of the lymph nodes, with area under curve (AUC) of 0.958, 0.937, 0.931, and 0.915, the corresponding cut-off values of 5.7 mm, 5.7 mm, 5.5 mm, and 4.8 mm, the corresponding sensitivities of 94.7%, 85.4%, 88.7%, and 79.4%, and the corresponding specificities of 93.7%, 96.3%, 86.2%, and 95.0%, respectively. The AUC of the thoracic paraesophageal lymph nodes, the subcarinal nodes and all regional lymph nodes were 0.845, 0.688, and 0.776, respectively. CONCLUSION: Region-based criterion for lymph node metastasis of thoracic ESCC is beneficial to improve the diagnostic efficiency of preoperative CT.

Survival impact of the number of lymph nodes dissection in patients receiving neoadjuvant chemotherapy for esophageal squamous cell carcinoma.

This study aimed to investigate the survival impact of the number of lymph nodes dissection (LND) in patients receiving neoadjuvant chemotherapy (NCT) for esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed the clinical pathological data and survival of 407 ESCC patients who underwent esophagectomy after NCT between January 2015 and December 2016. The relationship between the number of LNDs and 5-year overall survival (OS) or disease-free survival (DFS) was plotted by using restricted cubic spline analysis. A Cox proportional hazards regression model was used to identify prognostic factors of OS and DFS. We observed an obvious non-linear relationship between LND and the hazard ratios (HRs) for OS (P = 0.0015) and DFS (P < 0.001) of all the patients. In the multivariate analysis of OS and DFS, the number of LNDs (greater than 28 and less than 46) had a significant protective effect on survival (OS: HR: 0.61, 95% CI: 0.42-0.88, P = 0.007; DFS: HR: 0.50, 95% CI: 0.36-0.70, P < 0.001). For patients with nodal metastases, it was also an independent prognostic factor for OS (HR, 0.56, 95% CI, 0.35-0.90, P = 0.017) and DFS (HR, 0.42, 95% CI, 0.28-0.65, P < 0.001). Some degree of lymphadenectomy after NCT was beneficial in improving 5-year OS and DFS for ESCC patients with nodal metastases. For patients with nodal negativity, more extended lymphadenectomy did not improve patient survival.

Allosteric modulation of SHP2: Quest from known to unknown.

Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) is a key regulatory factor in the cell cycle and its activating mutations play an important role in the development of various cancers, making it an important target for antitumor drugs. Due to the highly conserved amino acid sequence and positively charged nature of the active site of SHP2, it is difficult to discover inhibitors with high affinity for the catalytic site of SHP2 and sufficient cell permeability, making it considered an "undruggable" target. However, the discovery of allosteric regulation mechanisms provides new opportunities for transforming undruggable targets into druggable ones. Given the limitations of orthosteric inhibitors, SHP2 allosteric inhibitors have become a more selective and safer research direction. In this review, we elucidate the oncogenic mechanism of SHP2 and summarize the discovery methods of SHP2 allosteric inhibitors, providing new strategies for the design and improvement of SHP2 allosteric inhibitors.

A Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer.

The WD40 repeat-containing F-box proteins (FBXWs) family belongs to three major classes of F-box proteins. Consistent with the function of other F-box proteins, FBXWs are E3 ubiquitin ligases to mediate protease-dependent protein degradation. However, the roles of several FBXWs remain elusive. In the present study, via integrative analysis of transcriptome profiles from The Cancer Genome Atlas (TCGA) datasets, we found that FBXW9 was upregulated in the majority of cancer types, including breast cancer. FBXW expression was correlated with the prognosis of patients with various types of cancers, especially for FBXW4, 5, 9, and 10. Moreover, FBXWs were associated with infiltration of immune cells, and expression of FBXW9 was associated with poor prognosis of patients receiving anti-PD1 therapy. We predicted several substrates of FBXW9, and TP53 was the hub gene in the list. Downregulation of FBXW9 increased the expression of p21, a target of TP53, in breast cancer cells. FBXW9 was also strongly correlated with cancer cell stemness, and genes correlated with FBXW9 were associated with several MYC activities according to gene enrichment analysis in breast cancer. Cell-based assays showed that silencing of FBXW9 inhibited cell proliferation and cell cycle progression in breast cancer cells. Our study highlights the potential role of FBXW9 as a biomarker and promising target for patients with breast cancer.

Molecular Mechanism of the Asarum-Angelica Drug Pair in the Treatment of Periodontitis Based on Network Pharmacology and Experimental Verification.

(1) To examine the potential mechanism of the Asarum-Angelica drug pair against periodontitis and provide an experimental basis for the treatment of periodontitis with herbal medicine. (2) The core components and core targets of the Asarum-Angelica drug pair in the treatment of periodontitis were detected according to network pharmacology methods. Finally, the effect of the Asarum-Angelica drug pair on osteogenic differentiation was observed in mouse embryonic osteoblast precursor cells. (3) According to the results of network pharmacology, there are 10 potential active ingredients in the Asarum-Angelica drug pair, and 44 potential targets were obtained by mapping the targets with periodontitis treatment. Ten potential active ingredients, such as kaempferol and ß-sitosterol, may play a role in treating periodontitis. Cell experiments showed that the Asarum-Angelica drug pair can effectively promote the expression of osteoblast markers alkaline phosphatase (ALP), Runt-related Transcription Factor 2 (RUNX2), and BCL2 mRNA and protein in an inflammatory environment (p < 0.05). (4) Network pharmacology effectively analyzed the molecular mechanism of Asarum-Angelica in the treatment of periodontitis, and the Asarum-Angelica drug pair can promote the differentiation of osteoblasts.

Design strategies and mechanisms of g-C3N4-based photoanodes for photoelectrocatalytic degradation of organic pollutants in water.

Emerging photoelectrocatalytic (PEC) systems integrate the advantages of photocatalysis and electrocatalysis and are considered as a promising technology for solving the global organic pollution problem in water environments. Among the photoelectrocatalytic materials applied for organic pollutant degradation, graphitic carbon nitride (CN) has the combined advantages of environmental compatibility, stability, low cost, and visible light response. However, pristine CN has disadvantages such as low specific surface area, low electrical conductivity, and high charge complexation rate, and how to improve the degradation efficiency of PEC reaction and the mineralization rate of organic matter is the main problem faced in this field. Therefore, this paper reviews the progress of various functionalized CN used for PEC reaction in recent years, and the degradation efficiency of these CN-based materials is critically evaluated. First, the basic principles of PEC degradation of organic pollutants are outlined. Then, engineering strategies to enhance the PEC activity of CN (including morphology control, elemental doping, and heterojunction construction) are focused on, and the structure-activity relationships between these engineering strategies and PEC activity are discussed. In addition, the important role of influencing factors on the PEC system is summarized in terms of mechanism, to provide guidance for the subsequent research. Finally, suggestions and perspectives are provided for the preparation of efficient and stable CN-based photoelectrocatalysts for practical wastewater treatment applications.