Poly (ionic liquid) cross-linked hydrogel encapsulated with AuPt nanozymes for the smartphone-based colorimetric detection of zearalenone.

A poly (ionic liquid) enhanced poly(acrylamide-acrylic acid) (PIL-PAM/AA) hydrogel-based colorimetric sensor was designed to detect zearalenone (ZEN). Different AuxPty nanoparticles were synthesized via the on-pot method. Through the kinetic analysis and the theoretical calculation, Au0.4Pt0.6 possessed the relatively low energy barriers to adsorb and decompose H2O2 so that it exhibited relatively better catalytic activity (Km = 2.02 × 10-3, Vmax = 6.14 × 10-7). AuPt nanoparticles were encapsulated into PIL-PAM/AA hydrogel via the interaction between aptamer and cDNA. In the presence of ZEN, the embedded AuPt nanoparticles were released to complete the catalytic reaction. Coupled with the smartphone application, the established method provided the linear range of 1-250 ng mL-1, with a detection limit of 0.6979 ng mL-1 for ZEN. Meanwhile, it also possessed excellent selectivity and good anti-interference performance. In wheat and corn samples, spiked recoveries were ranging from 75% to 113.30%.

Magnetite enhances As immobilization during nitrate reduction and Fe(II) oxidation by Acidovorax sp. strain BoFeN1.

Arsenic (As) cycling in groundwater is commonly coupled to the biogeochemical cycling of iron (Fe) and the associated transformation of Fe minerals present. Numerous laboratory studies suggested that Fe minerals can act as nucleation sites for further crystal growth and as catalysts for abiotic Fe(II) oxidation. In view of the widespread existence of magnetite in anoxic environments where As is often dissolved, we firstly exploited magnetite to enhance As immobilization during nitrate-reducing Fe(II) oxidation (NRFO) induced by Acidovorax sp. strain BoFeN1, a mixotrophic nitrate-reducing Fe(II)-oxidizing bacterium that can oxidize Fe(II) through both enzymatic and abiotic pathways. Subsequently, we investigated how magnetite affects NRFO and As immobilization. Results demonstrated a significant increase in As(III) removal efficiency from 75.4 % to 97.2 % with magnetite, attributed to the higher amount of NRFO and As(III) oxidation promoted by magnetite. It was found that magnetite stimulated the production of extracellular polymeric substances (EPS), which could decrease the diffusion of nitrate in the periplasm of bacteria and shield them against encrustation, resulting in a more rapid reduction of nitrate in the system with magnetite than that without magnetite. Meanwhile, Fe(II) was almost completely oxidized in the presence of magnetite during the whole 72 h experiment, while in the absence of magnetite, 47.7 % of Fe(II) remained, indicating that magnetite could obviously accelerate the chemical oxidation of Fe(II) with nitrite (the intermediates of nitrate bioreduction). Furthermore, the formation of labile Fe(III), an intermediate product of electron transfer between Fe(II) and magnetite, was reasonably deduced to be vital for anoxic As(III) oxidation. Additionally, the XPS analysis of the solid phase confirmed the oxidation of 43.8 % of As(III) to As(V). This study helps to understand the biogeochemical cycling of Fe and As in the environment, and provides a cost-effective and environmentally friendly option for in situ remediation of As-contaminated groundwater.

Pm57 from Aegilops searsii encodes a tandem kinase protein and confers wheat powdery mildew resistance.

Powdery mildew is a devastating disease that affects wheat yield and quality. Wheat wild relatives represent valuable sources of disease resistance genes. Cloning and characterization of these genes will facilitate their incorporation into wheat breeding programs. Here, we report the cloning of Pm57, a wheat powdery mildew resistance gene from Aegilops searsii. It encodes a tandem kinase protein with putative kinase-pseudokinase domains followed by a von Willebrand factor A domain (WTK-vWA), being ortholog of Lr9 that mediates wheat leaf rust resistance. The resistance function of Pm57 is validated via independent mutants, gene silencing, and transgenic assays. Stable Pm57 transgenic wheat lines and introgression lines exhibit high levels of all-stage resistance to diverse isolates of the Bgt fungus, and no negative impacts on agronomic parameters are observed in our experimental set-up. Our findings highlight the emerging role of kinase fusion proteins in plant disease resistance and provide a valuable gene for wheat breeding.

BL-B01D1, a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study.

BACKGROUND: Antibody-drug conjugates have promising clinical activity in the treatment of solid tumours. BL-B01D1 is a first-in-class EGFR-HER3 bispecific antibody-drug conjugate. We aimed to assess the safety and preliminary antitumour activity of BL-B01D1 in patients with locally advanced or metastatic solid tumours. METHODS: This first-in-human, open-label, multicentre, dose-escalation and dose-expansion phase 1 trial was conducted in seven hospitals in China, enrolling patients aged 18-75 years (dose escalation; phase 1a) or older than 18 years (dose expansion; phase 1b), with a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 0-1, and histologically or cytologically confirmed locally advanced or metastatic solid tumours that had progressed on current standard treatment. In the phase 1a i3+3 design, patients received intravenous BL-B01D1 at three different schedules: 0·27 mg/kg, 1·5 mg/kg, and 3·0 mg/kg weekly; 2·5 mg/kg, 3·0 mg/kg, and 3·5 mg/kg on days 1 and 8 of each cycle every 3 weeks; or 5·0 mg/kg and 6·0 mg/kg on day 1 of each cycle every 3 weeks. The primary objectives of phase 1a were to identify the safety, maximum tolerated dose, and dose-limiting toxicity. In phase 1b, patients were treated in two schedules: 2·5 and 3·0 mg/kg on days 1 and 8 every 3 weeks, or 4·5, 5·0, and 6·0 mg/kg on day 1 every 3 weeks. The primary objectives of phase 1b were to assess the safety and recommended phase 2 dose of BL-B01D1, and objective response rate was a key secondary endpoint. Safety was analysed in all patients with safety records who received at least one dose of BL-B01D1. Antitumour activity was assessed in the activity analysis set which included all patients who received at least one dose of BL-B01D1 every 3 weeks. This trial is registered with China Drug Trials, CTR20212923, and ClinicalTrials.gov, NCT05194982, and recruitment is ongoing. FINDINGS: Between Dec 8, 2021, and March 13, 2023, 195 patients (133 [65%] men and 62 [32%] women; 25 in phase 1a and 170 in phase 1b) were consecutively enrolled, including 113 with non-small-cell lung cancer, 42 with nasopharyngeal carcinomas, 13 with small-cell lung cancer, 25 with head and neck squamous cell carcinoma, one with thymic squamous cell carcinoma, and one with submandibular lymphoepithelioma-like carcinoma. In phase 1a, four dose-limiting toxicities were observed (two at 3·0 mg/kg weekly and two at 3·5 mg/kg on days 1 and 8 every 3 weeks; all were febrile neutropenia), thus the maximum tolerated dose was reached at 3·0 mg/kg on days 1 and 8 every 3 weeks and 6·0 mg/kg on day 1 every 3 weeks. Grade 3 or worse treatment-related adverse events occurred in 139 (71%) of 195 patients; the most common of which were neutropenia (91 [47%]), anaemia (76 [39%]), leukopenia (76 [39%]), and thrombocytopenia (63 [32%]). 52 (27%) patients had a dose reduction and five (3%) patients discontinued treatment due to treatment-related adverse events. One patient was reported as having interstitial lung disease. Treatment-related deaths occurred in three (2%) patients (one due to pneumonia, one due to septic shock, and one due to myelosuppression). In 174 patients evaluated for activity, median follow-up was 6·9 months (IQR 4·5-8·9) and 60 (34%; 95% CI 27-42) patients had an objective response. INTERPRETATION: Our results suggest that BL-B01D1 has preliminary antitumour activity in extensively and heavily treated advanced solid tumours with an acceptable safety profile. Based on the safety and antitumour activity data from both phase 1a and 1b, 2·5 mg/kg on days 1 and 8 every 3 weeks was selected as the recommended phase 2 dose in Chinese patients. FUNDING: Sichuan Baili Pharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

CD276 regulates the immune escape of esophageal squamous cell carcinoma through CXCL1-CXCR2 induced NETs.

BACKGROUND: CD276 (B7-H3), a pivotal immune checkpoint, facilitates tumorigenicity, invasiveness, and metastasis by escaping immune surveillance in a variety of tumors; however, the underlying mechanisms facilitating immune escape in esophageal squamous cell carcinoma (ESCC) remain enigmatic. METHODS: We investigated the expression of CD276 in ESCC tissues from patients by using immunohistochemistry (IHC) assays. In vivo, we established a 4-nitroquinoline 1-oxide (4NQO)-induced CD276 knockout (CD276wKO) and K14cre; CD276 conditional knockout (CD276cKO) mouse model of ESCC to study the functional role of CD276 in ESCC. Furthermore, we used the 4NQO-induced mouse model to evaluate the effects of anti-CXCL1 antibodies, anti-Ly6G antibodies, anti-NK1.1 antibodies, and GSK484 inhibitors on tumor growth. Moreover, IHC, flow cytometry, and immunofluorescence techniques were employed to measure immune cell proportions in ESCC. In addition, we conducted single-cell RNA sequencing analysis to examine the alterations in tumor microenvironment following CD276 depletion. RESULTS: In this study, we elucidate that CD276 is markedly upregulated in ESCC, correlating with poor prognosis. In vivo, our results indicate that depletion of CD276 inhibits tumorigenesis and progression of ESCC. Furthermore, conditional knockout of CD276 in epithelial cells engenders a significant downregulation of CXCL1, consequently reducing the formation of neutrophil extracellular trap networks (NETs) via the CXCL1-CXCR2 signaling axis, while simultaneously augmenting natural killer (NK) cells. In addition, overexpression of CD276 promotes tumorigenesis via increasing NETs' formation and reducing NK cells in vivo. CONCLUSIONS: This study successfully elucidates the functional role of CD276 in ESCC. Our comprehensive analysis uncovers the significant role of CD276 in modulating immune surveillance mechanisms in ESCC, thereby suggesting that targeting CD276 might serve as a potential therapeutic approach for ESCC treatment.

The patterns and risk factors for relapse in oesophageal squamous cell cancers that achieve pathological complete response to neoadjuvant chemoradiotherapy.

OBJECTIVES: The goal of this study was to investigate the patterns and risk factors for recurrence in patients with oesophageal squamous cell carcinoma with a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT). METHODS: Between January 2008 and December 2018, a total of 96 patients with pCR were enrolled in this study. Lymph nodes with a pCR [LN-ypCR response (+)] were defined as those lymph nodes without residual tumour but with the presence of treatment response to nCRT. Prognostic factors for recurrence-free survival (RFS) were analysed with Cox proportional hazards models and Fine-Gray competing risk models. Lymph node (LN) stations were counted according to the Japan Esophageal Society classification. RESULTS: The median follow-up time was 51.5 months. Recurrence occurred in 15 cases (15.6%) with a 9.9-month median time to recurrence and a 15.6-month median survival after recurrence. The majority of recurrent diseases developed within the first 2 years postoperatively. Distant recurrences were detected in 14 cases (14.6%), in which the most common recurrence sites were no.104 LN and the lung, followed by no.16 LN. The mean RFS in the whole cohort was 116.6 months. The LN-ypCR response (+) was identified as the independent prognostic factor for worse RFS in both the multivariate Cox model and the Fine-Gray competing risk model (P = 0.001 and P = 0.002, respectively). CONCLUSIONS: Relapse is not rare in oesophageal squamous cell carcinoma cases with pCR after nCRT. Distant recurrences, the predominant pattern of relapse, occur primarily within the first 2 years after oesophagectomy. Patients with pCR with an LN-ypCR response (+) have a higher risk for postoperative recurrence.

Diagnostic yield using electromagnetic navigation bronchoscopy for peripheral pulmonary nodules <2 cm.

BACKGROUND: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. OBJECTIVES: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. DESIGN: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. METHODS: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. RESULTS: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010). CONCLUSION: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

Multidrug resistance transporters P-gp and BCRP limit the efficacy of ATR inhibitor ceralasertib in cancer cells.

The therapeutic effect of chemotherapy and targeted therapy are known to be limited by drug resistance. Substantial evidence has shown that ATP-binding cassette (ABC) transporters P-gp and BCRP are significant contributors to multidrug resistance (MDR) in cancer cells. In this study, we demonstrated that a clinical-staged ATR inhibitor ceralasertib is susceptible to P-gp and BCRP-mediated MDR. The drug resistant cancer cells were less sensitive to ceralasertib compared to the parental cells. Moreover, ceralasertib resistance can be reversed by inhibiting the drug efflux activity of P-gp and BCRP. Interestingly, ceralasertib was able to downregulate the level of P-gp but not BCRP, suggesting a potential regulation between ATR signaling and P-gp expression. Furthermore, computational docking analysis predicted high affinities between ceralasertib and the drug-binding sites of P-gp and BCRP. In summary, overexpression of P-gp and BCRP are sufficient to confer cancer cells resistance to ceralasertib, underscoring their role as biomarkers for therapeutic efficacy.

Risk assessment of extra-uterine involvement and prognosis in young type I endometrial carcinoma with high or moderate differentiation and less than 1/2 myometrial invasion.

PURPOSE: The aim of this study was to investigate whether young patients with endometrial carcinoma can preserve adnexa and lymph nodes to improve their quality of life without compromising their prognosis. METHODS: A total of 319 patients with type I endometrial carcinoma (high or moderate differentiation and less than 1/2 myometrial invasion) hospitalized in the First Affiliated Hospital of Zhengzhou University from May 2012 to July 2021 were included. The patients were divided into four groups: high differentiation without myometrial invasion group (G1MI-), high differentiation with superficial myometrial invasion group (G1MI+), moderate differentiation without myometrial invasion group (G2MI-), and moderate differentiation with superficial myometrial invasion group (G2MI+). Logistic regression analysis was conducted to identify risk factors for extra-uterine involvement. Kaplan-Meier method was used to draw the survival curve to compare the prognosis in subgroups and rates of extra-uterine involvement were also compared using Chi-square test or Fisher's exact test. RESULTS: Multivariable logistic regression revealed that differentiation (HR = 14.590, 95%CI = 1.778-119.754, p = 0.013) and myometrial invasion (HR = 10.732, 95%CI = 0.912-92.780, p = 0.037) were the independent risk factors for extra-uterine involvement. The overall difference was statistically significant (p < 0.001). In the subgroups analysis, both adnexal metastasis and lymph node metastasis were statistically significant in the G2MI+ group compared with G1MI- (p = 0.007, p = 0.008). There were no significant differences in the overall survival (OS) rate and progression free survival (PFS) rate among the four subgroups (p > 0.05). CONCLUSIONS: Surgery with adnexal preservation and without systematic lymphadenectomy could be employed for the patients who are high differentiation with less than 1/2 myometrial invasion or moderate differentiation without myometrial invasion, but not recommended to the patients with moderate differentiation and superficial myometrial invasion.

Integrating bulk and single-cell sequencing data to construct a Scissor+ dendritic cells prognostic model for predicting prognosis and immune responses in ESCC.

Esophageal squamous cell carcinoma (ESCC) is characterized by molecular heterogeneity with various immune cell infiltration patterns, which have been associated with therapeutic sensitivity and resistance. In particular, dendritic cells (DCs) are recently discovered to be associated with prognosis and survival in cancer. However, how DCs differ among ESCC patients has not been fully comprehended. Recently, the advance of single-cell RNA sequencing (scRNA-seq) enables us to profile the cell types, states, and lineages in the heterogeneous ESCC tissues. Here, we dissect the ESCC tumor microenvironment at high resolution by integrating 192,078 single cells from 60 patients, including 4379 DCs. We then used Scissor, a method that identifies cell subpopulations from single-cell data that are associated bulk samples with genomic and clinical information, to stratify DCs into Scissorhi and Scissorlow subtypes. We applied the Scissorhi gene signature to stratify ESCC scRNAseq patient, and we found that PD-L1, TIGIT, PVR and IL6 ligand-receptor-mediated cell interactions existed mainly in Scissorhi patients. Finally, based on the Scissor results, we successfully developed a validated prognostic risk model for ESCC and further validated the reliability of the risk prediction model by recruiting 40 ESCC clinical patients. This information highlights the importance of these genes in assessing patient prognosis and may help in the development of targeted or personalized therapies for ESCC.

Characterization of Probiotic Properties and Whole-Genome Analysis of Lactobacillus johnsonii N5 and N7 Isolated from Swine.

In our previous microbiome profiling analysis, Lactobacillus (L.) johnsonii was suggested to contribute to resistance against chronic heat stress-induced diarrhea in weaned piglets. Forty-nine L. johnsonii strains were isolated from these heat stress-resistant piglets, and their probiotic properties were assessed. Strains N5 and N7 exhibited a high survival rate in acidic and bile environments, along with an antagonistic effect against Salmonella. To identify genes potentially involved in these observed probiotic properties, the complete genome sequences of N5 and N7 were determined using a combination of Illumina and nanopore sequencing. The genomes of strains N5 and N7 were found to be highly conserved, with two N5-specific and four N7-specific genes identified. Multiple genes involved in gastrointestinal environment adaptation and probiotic properties, including acidic and bile stress tolerance, anti-inflammation, CAZymes, and utilization and biosynthesis of carbohydrate compounds, were identified in both genomes. Comparative genome analysis of the two genomes and 17 available complete L. johnsonii genomes revealed 101 genes specifically harbored by strains N5 and N7, several of which were implicated in potential probiotic properties. Overall, this study provides novel insights into the genetic basis of niche adaptation and probiotic properties, as well as the genome diversity of L. johnsonii.

Regio- and Diastereoselective Hydrophosphination and Hydroamidation of gem-Difluorocyclopropenes.

In this study, concise, efficient, and modular hydrophosphinylation and hydroamidation of gem-difluorocyclopropenes were disclosed in a mild and transition-metal-free pattern. Through this approach, phosphorus, and nitrogen-containing gem-difluorocyclopropanes were produced in moderate to good yields with excellent regio- and diastereoselectivity. Readily available gem-difluorocyclopropenes and nucleophilic reagents, along with inexpensive inorganic bases, were employed. Multiple synthetic applications, including gram-scale and derivatization reactions and modification of bioactive molecules, were subsequently elaborated.

Whether surgical procedure can improve the prognosis of endometrial cancer arising in adenomyosis (EC-AIA)? A systematic review and meta-analysis.

PURPOSE: Endometrial cancer arising in adenomyosis (EC-AIA) is frequently detected accidentally following a general hysterectomy for adenomyosis. Whether supplemental lymphadenectomy in patients with EC-AIA can improve the survival outcome remains inconclusive. Herein, the authors summarized the data of patients with EC-AIA and further explored the impact of lymphadenectomy on the prognosis of these patients. METHODS: Five electronic databases, namely MEDLINE, Web of Science, PubMed, Embase, and the Cochrane Library were employed for searching articles from inception to May 2023. RESULTS: In total, 38 eligible studies enrolling 56 patients were included. Of these, 44 patients had a traceable prognosis. Kaplan-Meier curves demonstrated that patients who had undergone lymphadenectomy had a better progression-free survival (PFS) compared with those who had not undergone lymphadenectomy ( P =0.016), but there was no difference in overall survival. Univariable ( P =0.025, HR=0.25, 95% CI=0.08-0.84) and multivariable ( P =0.042, HR=0.13, 95% CI=0.020-0.930) Cox regression analyses revealed that lymphadenectomy was an independent protective factor for PFS. CONCLUSION: For patients diagnosed with EC-AIA following hysterectomy for benign disease, further supplementary lymphadenectomy is recommended to improve PFS.

Wheat powdery mildew resistance gene Pm13 encodes a mixed lineage kinase domain-like protein.

Wheat powdery mildew is one of the most destructive diseases threatening global wheat production. The wild relatives of wheat constitute rich sources of diversity for powdery mildew resistance. Here, we report the map-based cloning of the powdery mildew resistance gene Pm13 from the wild wheat species Aegilops longissima. Pm13 encodes a mixed lineage kinase domain-like (MLKL) protein that contains an N-terminal-domain of MLKL (MLKL_NTD) domain in its N-terminus and a C-terminal serine/threonine kinase (STK) domain. The resistance function of Pm13 is validated by mutagenesis, gene silencing, transgenic assay, and allelic association analyses. The development of introgression lines with significantly reduced chromosome segments of Ae. longissima encompassing Pm13 enables widespread deployment of this gene into wheat cultivars. The cloning of Pm13 may provide valuable insights into the molecular mechanisms underlying Pm13-mediated powdery mildew resistance and highlight the important roles of kinase fusion proteins (KFPs) in wheat immunity.

The Utilization of Metal-Organic Frameworks and Their Derivatives Composite in Supercapacitor Electrodes.

Up to now, the mainstream adoption of renewable energy has brought about substantial transformations in the electricity and energy sector. This shift has garnered considerable attention within the scientific community. Supercapacitors, known for their exceptional performance metrics like good charge/discharge capability, strong power density, as well as extended cycle longevity, have gained widespread traction across various sectors, including transportation and aviation. Metal-organic frameworks (MOFs) with unique traits including adaptable structure, highly customizable synthetic methods, and high specific surface area, have emerged as strong candidates for electrode materials. For enhancing the performance, MOFs are commonly compounded with other conducting materials to increase capacitance. This paper provides a detailed analysis of various common preparation strategies and characteristics of MOFs. It summarizes the recent application of MOFs and their derivatives as supercapacitor electrodes alongside other carbon materials, metal compounds, and conductive polymers. Additionally, the challenges encountered by MOFs in the realm of supercapacitor applications are thoroughly discussed. Compared to previous reviews, the content of this paper is more comprehensive, offering readers a deeper understanding of the diverse applications of MOFs. Furthermore, it provides valuable suggestions and guidance for future progress and development in the field of MOFs.

RNA modification-related genes illuminate prognostic signature and mechanism in esophageal squamous cell carcinoma.

Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m5C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6's function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.

The S-acylation cycle of transcription factor MtNAC80 influences cold stress responses in Medicago truncatula.

S-acylation is a reversible post-translational modification catalyzed by protein S-acyltransferases (PATs), and acyl protein thioesterases (APTs) mediate de-S-acylation. Although many proteins are S-acylated, how the S-acylation cycle modulates specific biological functions in plants is poorly understood. In this study, we report that the S-acylation cycle of transcription factor MtNAC80 is involved in the Medicago truncatula cold stress response. Under normal conditions, MtNAC80 localized to membranes through MtPAT9-induced S-acylation. In contrast, under cold stress conditions, MtNAC80 translocated to the nucleus through de-S-acylation mediated by thioesterases such as MtAPT1. MtNAC80 functions in the nucleus by directly binding the promoter of the glutathione S-transferase gene MtGSTU1 and promoting its expression, which enables plants to survive under cold stress by removing excess malondialdehyde and H2O2. Our findings reveal an important function of the S-acylation cycle in plants and provide insight into stress response and tolerance mechanisms.

Risk factors for pelvic and para-aortic lymph node metastasis in non-endometrioid endometrial cancer.

PURPOSE: The aim of this study was to evaluate the risk factors for pelvic lymph node metastasis (LNM) and para-aortic LNM in non-endometrioid endometrial cancer (non-EEC). METHODS: A total of 283 patients with non-EEC hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were included. Various characteristics were retrospectively analyzed in relation to LNM. RESULTS: Univariable and multivariable logistic regression analysis revealed cervical stromal invasion (OR = 3.441, 95% CI = 1.558-7.6, p = 0.002), myometrial invasion ≥1/2 (OR = 2.661, 95% CI = 1.327-5.337, p < 0.006), lymphovascular space involvement (LVSI) (OR = 4.118, 95% CI = 1.919-8.837, p < 0.001), positive peritoneal cytology (OR = 2.962, 95% CI = 1.344-6.530, p = 0.007), CA125 (OR = 1.002, 95% CI = 1-1.004, p = 0.026) were the independent risk factors for pelvic LNM. And myometrial invasion ≥1/2 (OR = 5.881, 95% CI = 2.056-16.427, p = 0.001), LVSI (OR = 4.962, 95% CI = 1.933-12.740, p = 0.001), adnexal (OR = 5.921, 95% CI = 2.003-17.502, p = 0.001) were the independent risk factors for para-aortic LNM. With the increase of independent risk factors, the rates of LNM were increased significantly. CONCLUSIONS: Cervical stromal invasion, myometrial invasion ≥1/2, LVSI, positive peritoneal cytology, and CA125 were risk factors for pelvic LNM. Myometrial invasion ≥1/2, LVSI and involvement of the adnexa were risk factors for para-aortic LNM which could provide a good basis to help predict which non-EEC patients are at higher risk for LNM.

Preclinical characterization and phase 1 results of ADG106 in patients with advanced solid tumors and non-Hodgkin's lymphoma.

ADG106, a ligand-blocking agonistic antibody targeting CD137 (4-1BB), exhibits promising results in preclinical studies, demonstrating tumor suppression in various animal models and showing a balanced profile between safety and efficacy. This phase 1 study enrolls 62 patients with advanced malignancies, revealing favorable tolerability up to the 5.0 mg/kg dose level. Dose-limiting toxicity occurs in only one patient (6.3%) at 10.0 mg/kg, resulting in grade 4 neutropenia. The most frequent treatment-related adverse events include leukopenia (22.6%), neutropenia (22.6%), elevated alanine aminotransferase (22.6%), rash (21.0%), itching (17.7%), and elevated aspartate aminotransferase (17.7%). The overall disease control rates are 47.1% for advanced solid tumors and 54.5% for non-Hodgkin's lymphoma. Circulating biomarkers suggest target engagement by ADG106 and immune modulation of circulating T, B, and natural killer cells and cytokines interferon γ and interleukin-6, which may affect the probability of clinical efficacy. ADG106 has a manageable safety profile and preliminary anti-tumor efficacy in patients with advanced cancers (this study was registered at ClinicalTrials.gov: NCT03802955).

The power and the promise of synthetic lethality for clinical application in cancer treatment.

Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.