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Silyl anions have garnered significant attention due to their synthetic abilities. However, previously reported silyl anions have been limited to either trigonal‐pyramidal or trigonal‐planar geometries, which confine them primarily as nucleophiles in substitution reactions. Herein, we report the isolation of the unprecedented T‐shaped planar silyl anion salt 2 by employment of a geometrically constrained triamido pincer ligand. Theoretical calculations disclosed that the silicon centre in 2 possesses both a lone pair of electrons and an empty 3pz orbital. In addition to nucleophilic substitution reactions with Ph3PAuCl and W(CO)6, 2 readily undergoes oxidative additions with CO2 and 2,6‐dimethylphenylisonitrile at room temperature. Furthermore, under mild conditions, compound 2 cleaves Csp2−H, Csp2−H, and H−H bonds in 1,2,4,5‐tetrafluorobenzene, an intramolecular iPr group, and dihydrogen, representing the first examples of C−H and H−H activations mediated by a silyl anion, respectively. This work unveils new reactivity of silyl anions owing to the non‐classical geometry and electronic structure. [ABSTRACT FROM AUTHOR]

The replacement of a CC unit with an isoelectronic BN unit in aromatic systems can give rise to molecules and materials with fascinating properties. We report here the synthesis, characterization, and reactivity of a 1,4,2,3‐diazadiborole species, 2, featuring an unprecedented 6π‐aromatic BN‐heterocyclic moiety that is isoelectronic to cyclopentadienide (Cp−). Bearing an unsymmetrical B=B entity, 2 exhibits reactivity toward oxidants, protic reagents, electrophiles, and unsaturated substrates. This reactivity facilitates the synthesis of a variety of novel mono‐ and bicyclic organoboron derivatives through mechanisms including ring retention, cleavage/recombination, annulation, and expansion. These findings reveal innovative synthetic routes to BN‐embedded aromatic compounds via desymmetrization, affording unique building blocks for synthetic chemistry. [ABSTRACT FROM AUTHOR]

Boron‐dipyrromethenes (BODIPYs) have attracted much attention owing to their unique properties and widespread applications; however, the incorporation of the heavier group 14 and 15 elements in the rigid dipyrromethene ligands remains limited. Herein, the dipyrromethene‐based heavier group 14 and 15 element complexes, tin‐dipyrromethene (SNDIPY, 1) and arsenic‐dipyrromethene (ASDIPY, 2), which are direct analogues of BODIPY, have been facilely synthesized and isolated in moderate yields. Both compounds have been investigated by NMR, UV‐vis absorption, photoluminescence spectroscopy, cyclic voltammogram, X‐ray crystallography, as well as theoretical studies. Both compounds exhibit green photoluminescence. Notably, SNDIPY 1 is air‐stable and compound 2 represents the first isolable and structurally characterized ASDIPY. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MS) has a high prevalence in hemodialysis patients. High asprosin levels are associated with the accumulation of adiposity and an increase in body weight, which may drive the development of this syndrome. The relationship between asprosin and MS in patients on hemodialysis has not been investigated. We enrolled hemodialysis patients at the hemodialysis center of one hospital in May 2021. MS was defined by the International Diabetes Federation. Fasting serum asprosin levels were measured. ROC curve, multivariate logistic regression and Spearman's rank correlation analyses were performed. In total, 134 patients were included, with 51 with MS and 83 without MS. Among the patients with MS, there was a significantly higher proportion of women (54.9%), prevalence of DM (p < 0.001), waist circumference (p < 0.001), BMI (p < 0.001), triglycerides (p < 0.001), and low-density lipoprotein cholesterol(p < 0.050), and PTH (p < 0.050) contents and a lower diastolic pressure(p < 0.050) and high-density lipoprotein cholesterol level (p < 0.001) than those in patients without MS. The patients with MS exhibited significantly higher serum asprosin levels than the non-MS patients [502.2 ± 153.3 ng/ml vs. 371.5 ± 144.9 ng/ml, p < 0.001]. The AUC for the serum asprosin level was 0.725 (95% confidence interval: 0.639, 0.811). Multivariate logistic regression analysis revealed that asprosin was independently and significantly positively associated with MS (OR = 1.008, p < 0.010). Asprosin levels tended to rise as the number of diagnostic criteria of MS increased (p for trend <0.001). Fasting serum asprosin is positively correlated with MS and could be an independent risk factor for MS in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Müller's hydrocarbon and its analogues are classical examples of Kekulé diradicaloids and have gained great attention. However, because of their high reactivities, their isolation and structural characterizations are still challenging. Herein, we report the isolation of two bis‐BN‐based analogues of Müller's hydrocarbon (1 and 2) as crystalline solids in moderate yields. Experimental results and theoretical studies demonstrated that compound 1 possessing the terminal 1,3,2‐diazaboryl groups is an open‐shell singlet diradicaloid, which is in contrast to the closed‐shell singlet ground states of the bis‐BN‐based analogues of Thiele's and Chichibabin's hydrocarbons with the same terminal groups, illustrating the strong influence of the central linkers on the ground state. Additionally, the replacement of the terminal 1,3,2‐diazaboryl groups in 1 with the bis(2,4,6‐triisopropylphenyl)boryl groups affords 2 with higher diradical character and a smaller singlet‐triplet energy gap. [ABSTRACT FROM AUTHOR]

This report unveils an advancement in the formation of a Lewis superacid (LSA) and an organic superbase by the geometrical deformation of an organoboron species towards a T‐shaped geometry. The boron dication [2]2+ supported by an amido diphosphine pincer ligand features both a large fluoride ion affinity (FIA>SbF5) and hydride ion affinity (HIA>B(C6F5)3), which qualifies it as both a hard and soft LSA. The unusual Lewis acidic properties of [2]2+ are further showcased by its ability to abstract hydride and fluoride from Et3SiH and AgSbF6 respectively, and effectively catalyze the hydrodefluorination, defluorination/arylation, as well as reduction of carbonyl compounds. One and two‐electron reduction of [2]2+ affords stable boron radical cation [2]⋅+ and borylene 2, respectively. The former species has an extremely high spin density of 0.798e at the boron atom, whereas the latter compound has been demonstrated to be a strong organic base (calcd. pKBH+ (MeCN)=47.4) by both theoretical and experimental assessment. Overall, these results demonstrate the strong ability of geometric constraining to empower the central boron atom. [ABSTRACT FROM AUTHOR]

Azithromycin eye drops with a bioadhesive ocular drug‐delivery system can offer a simplified dosing regimen. In this study, we compared the pharmacokinetic properties and assessed the bioequivalence of a newly developed generic azithromycin eye drop with a branded formulation. This open‐label, single‐dose, randomized, crossover, sparse‐sampling ocular bioequivalence study was conducted on 48 healthy Chinese volunteers. Tear samples were collected for up to 36 hours, and each participant was randomly allocated to one of the prespecified sampling times. Tear drug concentrations were determined using a validated liquid chromatography‐tandem mass spectrometry method. The pharmacokinetic parameters were calculated via noncompartmental analysis. A nonparametric bootstrap method was used to obtain 90% confidence intervals (CIs) for the ratios of the test and reference drugs. Tolerability was evaluated for adverse events (AEs). After bootstrapping (1000 iterations), the 90%CIs for the log‐transformed ratios of Cmax, AUC0‐t, and AUC0–∞were within the acceptable bioequivalence range (80%–125%). No moderate‐to‐severe AEs were reported for either formulation. Bioequivalence was demonstrated between the two formulations. The sparse‐sampling design with the bootstrapping technique is promising for bioequivalence studies of topical ophthalmic drugs. [ABSTRACT FROM AUTHOR]

What Is Known and Objective. Elevated serum uric acid (SUA) is one of the most common adverse reactions during the administration of pyrazinamide, but patients exhibit significant individual differences. This study aimed to evaluate the relationship between gene polymorphisms and pyrazinamide-induced SUA elevation in Han Chinese tuberculosis patients. Methods. Tuberculosis patients treated with pyrazinamide were genotyped for the following three candidate genes: SLC22A12, SLC2A9, and ABCG2. Patients were divided into low-risk and high-risk groups according to the change of SUA after treatment. Intergroup comparisons were performed on clinical characteristics, allele and genotype frequencies, and haplotype distributions, and logistic regression analysis was used to explore the relevant risk factors. Results. In total, 143 patients were enrolled, including 83 in the high-risk groups and 60 in the low-risk groups. We observed a significant association between SLC2A9 polymorphism and pyrazinamide-induced SUA elevation. The G allele was significantly lower in the high-risk group than in the low-risk group (27.7% vs. 48.3%, OR = 0.410, 95% CI: 0.250–0.671, p < 0.001). Patients with the GA and GG genotypes were less likely to have SUA elevation than those with the AA genotype (OR = 0.125, 95% CI: 0.053–0.293, p < 0.001 and OR = 0.252, 95% CI: 0.074–0.851, p = 0.026 , respectively). Regarding SLC2A9 rs13129697, the frequency of the G allele was significantly lower in the high-risk group than in the low-risk group (26.1% vs. 40.8%, OR = 0.531, 95% CI: 0.312–0.842, p = 0.008). In the low-risk group, the proportion of patients with the TG genotype was significantly higher than that with the TT genotype (81.7% vs. 18.3%, OR = 0.279, 95% CI: 0.127–0.611, p = 0.001). Haplotype analysis revealed that patients with the SLC2A9 (rs1014290–rs13129697) GG haplotype had lower risk of SUA elevation than those with the AT haplotype (27.11% vs. 63.25%, p = 0.005). Furthermore, logistic regression analysis showed that drinking history was an independent risk factor for elevated SUA caused by PZA (OR = 3.943, 95% CI = 1.18–13.175, p = 0.026) and that the rs1014290 GA genotype might be a protective factor (OR = 0.094, 95% CI = 0.023–0.386, p = 0.001) after correction. What Is New and Conclusion. We found that SLC2A9 genetic polymorphisms were associated with elevated SUA caused by pyrazinamide. The G>A variant of rs1014290 and drinking history might be risk factors. [ABSTRACT FROM AUTHOR]

Low temperature is the main factor for global natural disasters affecting the growth and distribution of plants, and cotton may be affected by low temperature and cold damage at all growth stages. In addition, the insecticidal resistance of cultivars has been reported to perform poorly or unstably due to adverse environments. The present study aimed to investigate the impact of low temperature on the levels of insecticidal protein in Bacillus thuringiensis (Bt) transgenic cotton plants during the peak boll stage. To achieve this, two Bt cotton cultivars, Sikang1 (SK1) and Sikang3 (SK3), were subjected to different temperature regimes and durations. The findings of the study demonstrated that the expression of insecticidal protein in the boll shell of Bt transgenic cotton plants was significantly inhibited under low-temperature stress. Specifically, in 2020, compared to the CK (27 °C), the insecticidal protein content in the boll shell of SK3 decreased by 28.19% after a 48 h of a 16 °C temperature. These results suggest that low-temperature stress can negatively impact the expression of insecticidal protein in Bt transgenic cotton, highlighting the need for appropriate measures to minimize its adverse effects on cotton production. In addition, the threshold temperature that leads to a significant decrease in the content of insecticidal proteins symbolizes an upward trend as the duration of stress prolongs. Decreased Bt protein content at low temperatures is associated with changes in the N metabolism. The present study revealed a significant positive correlation between the levels of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities, as well as in the soluble protein levels in the boll shell and the content of the Bt protein. On the other hand, a significant negative correlation was observed between the levels of free amino acids, peptidase, and protease activities, as well as of Bt protein content. These findings suggest that, in Bt cotton production, it is crucial to remain vigilant of prolonged low-temperature disasters, which last for over 12 h and drop below 17–20 °C during the peak boll stage. Such conditions may reduce insecticidal resistance, leading to substantial economic losses. [ABSTRACT FROM AUTHOR]

Naked cuticle homolog 1 (NKD1), which is expressed at low levels in many tumors, is considered an inhibitor of the Wnt/β‐catenin pathway, but it is highly expressed in colon cancer and can promote colon cancer cell proliferation. miRNAs are involved in the occurrence and progression of many tumors. However, miRNAs that can regulate NKD1 and the mechanisms by which NKD1 regulates tumor progression remain ambiguous. This research aims to reveal the potential regulatory network of NKD1 in colon cancer. miRNA data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed by bioinformatics to screen for potential miRNAs targeting NKD1. Let‐7b‐5p was found to inhibit proliferation, migration, and invasion of colon cancer cells targeting NKD1. Further studies suggested that let‐7b‐5p can modulate Wnt signaling activity, and the nuclear accumulation of β‐catenin was significantly restrained by let‐7b‐5p through targeting NKD1. Moreover, NKD1 could prohibit the expression of the APC protein. Further studies manifested that NKD1 bound to APC and promoted the ubiquitination degradation of APC through restraining the expression of the deubiquitinating enzyme USP15 and blocking the combination between USP15 and APC. Functionally, NKD1 enhanced the proliferation and migration of colon cancer cells by inhibiting APC expression. This research revealed a novel mechanism by which the let‐7b‐5p‐NKD1‐APC‐β‐catenin signaling pathway inhibited colon cancer cell progression. [ABSTRACT FROM AUTHOR]

The heaviest pnictogen-dipyrromethenes DPMPnCl2 (Pn = Sb, 3; Bi 4), which are direct analogues of boron-dipyrromethene (BODIPY), have been readily prepared and isolated as crystalline solids. Both compounds display green photoluminescence with small full widths at half maximum in toluene. Moreover, the reduction of 3 with sodium metal afforded the cyclic dicoordinate stibinidene 5. [ABSTRACT FROM AUTHOR]

Linezolid, an oxazolidinone antibacterial agent with several formulations, has been widely used for over 20 years. This study aimed to compare the bioequivalence, pharmacokinetics, and safety of test and reference linezolid tablets after a single oral dose under fasting/fed conditions. In this open‐label, randomized, two‐period, crossover, bioequivalence study, 48 healthy volunteers were enrolled equally to fasting or fed groups to receive one 600‐mg test or reference linezolid tablet in each period. Pharmacokinetic parameters were calculated using noncompartmental methods. Adverse events (AEs) were recorded to assess safety. The geometric mean terminal half‐lives of test and reference formulations were 3.8 and 3.6 hours, respectively, under both fasting and fed conditions. The median time to reach the maximum observed concentration was 1.0 hour (both formulations) in the fasting group, and 2.0 hours (test formulation) and 2.5 hours (reference formulation) in the fed group. No substantial differences were observed in the area under plasma concentration–time curve (AUC) from time 0 to the last sampling time (AUC0‐t) and the maximum observed concentration (Cmax) between formulations. Geometric least square mean ratios for Cmax, AUC0‐t, and AUC from time 0 to infinity were approximately 100%, and the corresponding 90% confidence intervals for bioequivalence were within 80%–125%. Ten participants reported 11 AEs; AEs were mild, except for one pregnancy event with an outcome of induced absorption. Bioequivalence between the two linezolid formulations was demonstrated under fasting and fed conditions, and a similar safety profile was observed among healthy Chinese volunteers. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Both dipyrromethene complexes and radicals of heavier main group elements have been of high interest. However, cationic germanium radicals and dipyrromethene‐based radicals of heavier main group elements are still escaped to be isolated. Herein, we report the isolation and full characterization of a neutral Ge(I)‐masked dipyrromethene‐based radical 3 and the first cationic Ge(III)‐centered radical 5·+ as stable crystalline solids. 3 behaves as a germanium(I) radical in its reaction with diphenyl disulfide to form the Ge—S bond, although X‐ray crystallographic, EPR spectroscopic, computational studies revealed that the unpaired electron of 3 is mainly delocalized over the C9N2Ge backbone and the allylic radical character is also significant in 3. In contrast to 3, the spin density of 5·+ is mainly localized at the Ge center with minor contribution from the dipyrromethene ligand. Moreover, reduction of 5·+ with potassium graphite quantitatively regenerates 5, illustrating a reversible one‐electron redox pair. [ABSTRACT FROM AUTHOR]

What Is Known and Objective: Patients with optic neuritis (ON) have significant individual differences in their response to high‐dose intravenous methylprednisolone (HIMP) therapy. This study aims to evaluate the association between gene polymorphisms and the efficacy of HIMP therapy in Chinese Han patients with ON mediated by aquaporin‐4 immunoglobulin G antibody (AQP4‐IgG) ‐positive neuromyelitis optica spectrum disorder (NMOSD) or multiple sclerosis (MS). Methods: Chinese Han patients with AQP4‐IgG+ NMOSD‐ON or MS‐ON were genotyped for four candidate genes: ABCB1 (rs1045642, rs1128503, rs2032582), NR3C1 (rs41423247), TBX21 (rs9910408, rs16947078) and VDR (rs731236, rs1544410, rs7975232, rs2228570). Patients were divided into glucocorticoid resistance (GR) and glucocorticoid sensitivity (GS) groups based on vision acuity (VA) improvement after HIMP treatment. Intergroup comparisons were performed on clinical characteristics, allele and genotype frequencies and haplotype distributions. Results: A total of 267 patients completed the follow‐up, including 120 patients with AQP4‐IgG+ NMOSD‐ON and 147 patients with MS‐ON. We observed a significant association between the ABCB1 G2677T/A (rs2032582) polymorphism and glucocorticoid response in AQP4‐IgG+ NMOSD‐ON patients. Changes in VA scores in patients with the GG genotype were significantly lower than those in patients with the T/A T/A genotype (1.07 ± 1.20 vs. 1.77 ± 1.31, p = 0.026). In the GS group, the G allele had a lower frequency than the T/A allele (32.03% vs. 60.16%, p = 0.001). Logistic regression analysis showed that the G2677T/A GG and G T/A genotypes could increase the GR risk 3.53 and 2.67 times compared with the T/A T/A genotype, respectively (OR = 3.534, 95% CI: 1.186–10.527, p = 0.023; OR = 2.675, 95% CI: 1.005–7.123, p = 0.049). In addition, haplotype analysis showed that AQP4‐IgG+ NMOSD‐ON patients with the TAT/TTT haplotype (ABCB1 C3435T‐G2677T/A‐C1236T) were only 0.54 times more likely to develop GR than those with other haplotypes (OR = 0.542, 95% CI: 0.315–0.932, p = 0.026). However, we did not observe intergroup differences in the MS‐ON population. What Is New and Conclusion: Our findings suggest that the G > T/A polymorphism of ABCB1 G2677T/A and the TAT/TTT haplotype played a protective role in HIMP treatment of AQP4‐IgG+ NMOSD‐ON but not MS‐ON. [ABSTRACT FROM AUTHOR]

Misoprostol is a synthetic prostaglandin E1 derivative that has been used to treat duodenal and gastric ulcers, and to prevent ulcers caused by nonsteroidal anti‐inflammatory drugs in many countries. Misoprostol can also be used for medical abortion. This study aimed to investigate the pharmacokinetic profiles of misoprostol tablets (test product) by comparing them with Cytotec (200 μg) (reference product). To assess the bioequivalence between test and reference products, a two‐sequence, two‐period crossover study was conducted with 48 healthy Chinese subjects enrolled under fasting conditions. A validated liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) assay was used to determine the concentration of misoprostol acid in plasma. A mixed model analysis of variance was used to calculate the bioequivalence of pharmacokinetic (PK) parameters. The point estimate of geometric mean ratios with 90% confidence intervals for the maximum observed concentration (Cmax) and the area under the concentration‐time curve (AUC0‐t) for misoprostol acid in reference and test products were 107.8% and 106.5%, respectively (range 80%–125%). Additionally, none of the secondary PK parameters presented significant differences. No severe or more than moderate adverse events were detected in the 48 subjects. However, one subject discontinued the treatment due to drug‐related gastrointestinal reactions. All adverse events were mild with rates of 19.2% and 22.9% after the administration test and reference products, respectively. Overall, the bioequivalence between the two misoprostol products was demonstrated in fasting conditions, and all subjects tolerated both treatments. [ABSTRACT FROM AUTHOR]

The article titled "[Retracted] Zearalenone regulates endometrial stromal cell apoptosis and migration via the promotion of mitochondrial fission by activation of the JNK/Drp1 pathway" published in Molecular Medicine Reports in 2018 has been retracted due to concerns about the experimental design and presentation of data in Figure 5. An internal investigation confirmed anomalies in the figure, leading to a lack of confidence in the data presented. The authors did not provide an explanation for the concerns raised, resulting in the retraction of the article. [Extracted from the article]

Two radical cations of bis-BN-based analogues of Thiele's hydrocarbons were facilely synthesized, fully characterized, and theoretically investigated. One-electron oxidation leads to the reduced bond length alternation and NICS values of the central C4N2 rings, suggesting the decreasing antiaromatic character. The spin density of the radical cations is significantly delocalized over the central linkers with a small contribution from two terminal N-heterocyclic boryl units. [ABSTRACT FROM AUTHOR]

Increased endometrial stromal cell (ESC) survival and migration is responsible for the development and progression of endometriosis. However, little is known about the mechanisms underlying ESC survival and migration, and limited therapeutic strategies that are able to reverse these abnormalities are available. The present study investigated the effects of zearalenone (ZEA) on ESC survival and migration, particularly focusing on mitochondrial fission and the c‑Jun N‑terminal kinase (JNK)/dynamin‑related protein 1 (Drp1) pathway. The results revealed that ZEA induced ESC apoptosis in a dose‑dependent manner. Furthermore, ZEA treatment triggered excessive mitochondrial fission resulting in structural and functional mitochondrial damage, leading to the collapse of the mitochondrial membrane potential and subsequent leakage of cytochrome c into the cytoplasm. This triggered the mitochondrial pathway of apoptosis. Additionally, ZEA‑induced mitochondrial fission decreased ESC migration through F‑actin/G‑actin homeostasis dysregulation. ZEA also increased JNK phosphorylation and subsequently Drp1 phosphorylation at the serine 616 position, resulting in Drp1 activation. JNK/Drp1 pathway inhibition abolished the inhibitory effects of ZEA on ESC survival and migration. In summary, the present study demonstrated that ZEA reduced ESC survival and migration through the stimulation of mitochondrial fission by activation of the JNK/Drp1 pathway. [ABSTRACT FROM AUTHOR]

Extrachromosomal DNAs (eccDNAs) frequently carry amplified oncogenes. This investigation aimed to examine the occurrence and role of eccDNAs in individuals diagnosed with advanced perihilar cholangiocarcinoma (pCCA) who exhibited distinct prognostic outcomes. Five patients with poor survival outcomes and five with better outcomes were selected among patients who received first-line hepatic arterial infusion chemotherapy from June 2021 to June 2022. The extracted eccDNAs were amplified for high-throughput sequencing. Genes associated with the differentially expressed eccDNAs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The differentially expressed bile eccDNA-related genes were used to construct a prognostic model. Across all 10 patients, a total of 19,024 and 3,048 eccDNAs were identified in bile and plasma, respectively. The concentration of eccDNA detected in the bile was 9-fold higher than that in plasma. The chromosome distribution of the eccDNAs were similar between bile and matched plasma. GO and KEGG pathway analyses showed enrichment in the mitogen-activated protein kinase (MAPK) and Wnt/β-catenin pathways in patients with poor survival outcomes. According to the prognostic model constructed by eccDNA-related genes, the high-risk group of cholangiocarcinoma patients displayed significantly shorter overall survival ( p < 0.001). Moreover, the degree of infiltration of immunosuppressive cells was higher in patients in the high-risk group. In conclusion, EccDNA could be detected in bile and plasma of pCCA patients, with a higher concentration. A prognostic model based on eccDNA-related genes showed the potential to predict the survival and immune microenvironment of patients with cholangiocarcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fu, Dai, Zhang, Zheng, Cao, Xu, Zhong, Niu and Wang.)

Low temperature delayed cotton growth, increased abscission of reproductive organs, and seriously reduced quality and yield. Moreover, failed or unstable performance of insecticidal resistance due to adverse environments have been reported. In order to study the impact of low temperature on the insecticidal protein contents at square stage in Bacillus Thuringenesis (Bt) transgenic cotton, different temperature regimes and durations were imposed on two Bt cotton cultivars, Sikang1 (the conventional cultivar, SK1) and Sikang3 (the hybrid cultivar, SK3). Low temperature stress exhibited a significant inhibitory effect on insecticidal protein expression in squares and leaves of Bt transgenic cotton plants, with insecticidal protein contents decreased up to 30% with decreasing temperature. In addition, the threshold temperature resulting in significant reduction of insecticidal protein contents symbolized a rising trend as stress duration extended, together with a greater reduction observed. Thus, at square stage, the detrimental influence of low temperature on Bt protein contents was closely related to the low temperature level and duration. The square Bt protein content was positively correlated with leaf Bt protein content, but was more sensitive to low temperature. Across the whole treatment duration in both years, square Bt protein level was significantly negatively correlated with malondialdehyde (MDA) contents, as well as the activities of catalase (CAT) and superoxide dismutase (SOD), indicating the negative effect of cold induced oxidative stress on Bt protein contents. The reduced Bt protein contents under low temperature were also related to altered N metabolism. Glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities, as well as soluble protein contents in squares reduced, and greater reduction was recorded with decreasing temperature. In contrast, the free amino acid contents, and peptidase and protease activities increased, and greater elevation was noted with decreasing temperature. These results suggested in Bt cotton production, it is necessary to be alert to low temperature disasters that may last for more than 24 hours and lower than 15-17°C during the square stage, which may lead to reduced insecticidal resistance causing serious economic losses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Liu, Dai, Yue, Liu, Li, He, Zhang and Chen.)

Background: Gastric cancer (GC) ranks fifth in prevalence among carcinomas worldwide. Both pyroptosis and long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and development of gastric cancer. Therefore, we aimed to construct a pyroptosis-associated lncRNA model to predict the outcomes of patients with gastric cancer., Methods: Pyroptosis-associated lncRNAs were identified through co-expression analysis. Univariate and multivariate Cox regression analyses were performed using the least absolute shrinkage and selection operator (LASSO). Prognostic values were tested through principal component analysis, a predictive nomogram, functional analysis and Kaplan‒Meier analysis. Finally, immunotherapy and drug susceptibility predictions and hub lncRNA validation were performed., Results: Using the risk model, GC individuals were classified into two groups: low-risk and high-risk groups. The prognostic signature could distinguish the different risk groups based on principal component analysis. The area under the curve and the conformance index suggested that this risk model was capable of correctly predicting GC patient outcomes. The predicted incidences of the one-, three-, and five-year overall survivals exhibited perfect conformance. Distinct changes in immunological markers were noted between the two risk groups. Finally, greater levels of appropriate chemotherapies were required in the high-risk group. AC005332.1, AC009812.4 and AP000695.1 levels were significantly increased in gastric tumor tissue compared with normal tissue., Conclusions: We created a predictive model based on 10 pyroptosis-associated lncRNAs that could accurately predict the outcomes of GC patients and provide a promising treatment option in the future.

Background: TGF-β signaling pathway plays an essential role in tumor progression and immune responses. However, the link between TGF-β signaling pathway-related genes (TSRGs) and clinical prognosis, tumor microenvironment (TME), and immunotherapy in gastric cancer is unclear. Methods: Transcriptome data and related clinical data of gastric cancer were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and 54 TSRGs were obtained from the Molecular Signatures Database (MSigDB). We systematically analyzed the expression profile characteristics of 54 TSRGs in 804 gastric cancer samples and examined the differences in prognosis, clinicopathological features, and TME among different molecular subtypes. Subsequently, TGF-β-related prognostic models were constructed using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to quantify the degree of risk in each patient. Patients were divided into two high- and low-risk groups based on the median risk score. Finally, sensitivity to immune checkpoint inhibitors (ICIs) and anti-tumor agents was assessed in patients in high- and low-risk groups. Results: We identified two distinct TGF-β subgroups. Compared to TGF-β cluster B, TGF-β cluster A exhibits an immunosuppressive microenvironment with a shorter overall survival (OS). Then, a novel TGF-β-associated prognostic model, including SRPX2, SGCE, DES, MMP7, and KRT17, was constructed, and the risk score was demonstrated as an independent prognostic factor for gastric cancer patients. Further studies showed that gastric cancer patients in the low-risk group, characterized by higher tumor mutation burden (TMB), the proportion of high microsatellite instability (MSI-H), immunophenoscore (IPS), and lower tumor immune dysfunction and exclusion (TIDE) score, had a better prognosis, and linked to higher response rate to immunotherapy. In addition, the risk score and anti-tumor drug sensitivity were strongly correlated. Conclusion: These findings highlight the importance of TSRGs, deepen the understanding of tumor immune microenvironment, and guide individualized immunotherapy for gastric cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zeng, He, Dai, Lu, Deng, Zhu, Liu, Liu, Lu, Wang and Jin.)

Background: Cuproptosis is a novel type of cell death induced by copper. Cuproptosis-associated genes play a crucial part in oncogenesis and the growth and metastasis of tumors. However, the correlations among cuproptosis-associated genes, overall survival, the tumor microenvironment, and drug sensitivity remain unclear. Therefore, we performed an analysis of cuproptosis-associated genes across cancers. Methods: We downloaded RNA sequence expression data, clinical and survival data, stemness score data, and immune subtype data of cuproptosis-associated genes from the UCSC Xena. Next, we conducted differential analysis, expression analysis and correlation analysis across cancers with various R packages. Moreover, survival analysis and Cox hazard analysis were conducted to investigate the relationships between cuproptosis-associated genes and survival outcomes in various cancer types. Finally, we also analyzed the relationship among the levels of cuproptosis-associated genes across cancers, immune types, the tumor microenvironment, stemness scores, and drug sensitivity. Expression validation of cuproptosis-associated genes in renal cancer and normal tissues by immunohistochemical staining. Results: We found that 10 cuproptosis-associated genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, and CDKN2A) were differently expressed in 18 tumors and normal tissues. Survival outcomes showed that cuproptosis-associated genes had prognostic value in various cancer types. Moreover, we identified that cuproptosis-associated genes had different levels in six immune subtypes. The study also indicated that the levels of most cuproptosis-associated genes were positively correlated with the RNAss and DNAss. FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, and PDHB were negatively correlated with immune scores and ESTIMATE scores. In addition, we identified the top 16 drugs strongly sensitivity to cuproptosis-associated genes according to the correlation coefficient. Finally, we also found that cuproptosis-associated genes were significantly correlated with immune subtype, clinical features, the tumor microenvironment, and drug sensitivity in Kidney renal clear cell carcinoma. And the results of immunohistochemical staining analysis was very consistent with the previous analysis. Conclusion: We performed an overall analysis to uncover the roles of cuproptosis-associated genes in differential expression, survival outcomes, immune subtypes, the tumor microenvironment, stemness scores, and cancer drug sensitivity across cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Lu, Dai, Shen, Zeng, Liu, Yu, Deng and Lu.)

Background: Cellular senescence is a novel hallmark of cancer associated with patient outcomes and tumor immunotherapy. However, the value of cellular senescence-related long non-coding RNAs (lncRNAs) in predicting prognosis and immunotherapy response for stomach adenocarcinoma (STAD) patients needs further investigation. Methods: The transcriptome and corresponding clinical information of STAD and cellular senescence-related genes were, respectively, downloaded from the Cancer Genome Atlas (TCGA) and CellAge databases. Differential expression analysis and coexpression analysis were performed to obtain cellular senescence-related lncRNAs. Univariate regression analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis were conducted to establish the cellular senescence-related lncRNA prognostic signature (CSLPS). Next, the survival curve, ROC curve, and nomogram were developed to assess the capacity of predictive models. Moreover, principal component analysis (PCA), gene set enrichment analysis (GSEA), tumor microenvironment (TME), tumor mutation burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion (TIDE) score analysis were performed between high- and low-risk groups. Results: A novel CSLPS involving fifteen lncRNAs (REPIN1-AS1, AL355574.1, AC104695.3, AL033527.2, AC083902.1, TYMSOS, LINC00460, AC005165.1, AL136115.1, AC007405.2, AL391152.1, SCAT1, AC129507.1, AL121748.1, and ADAMTS9-AS1) was developed. According to the nomogram, the risk model based on the CSLPS was an independent prognostic factor and could predict 1-, 3-, and 5-year overall survival for STAD patients. GSEA suggested that the high-risk group was mainly associated with Toll-like receptor, JAK/STAT, NOD-like receptor, and chemokine signaling pathways. Further analysis revealed that STAD patients in the low-risk group with better clinical outcomes had a higher TMB, higher proportion of high microsatellite instability (MSI-H), better immune infiltration, and lower TIDE scores. Conclusion: A fifteen-CSlncRNA prognostic signature could predict survival outcomes, and patients in the low-risk group may be more sensitive to immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zeng, Liu, He, Lu, Dai, Qi, Liu, Deng, Lu, Jin and Liu.)

BACKGROUND Genetic correlations with the response to intranasal corticosteroids (INCS) in seasonal allergic rhinitis (SAR) treatment are unknown. This study aimed to evaluate the role of gene polymorphisms in the response to INCS in Chinese Han patients with moderate to severe SAR. MATERIAL AND METHODS In this study, 286 Chinese Han patients with SAR were genotyped for 4 candidate genes: the glucocorticosteroid receptor (NR3C1) gene, glucocorticoid-induced transcription factor 1 (GLCCI1) gene, T-box 21 gene (TBX21), and ATP binding cassette subfamily B member 1 (ABCB1) gene. Patients were treated with INCS for 4 weeks. The total nasal symptom score (TNSS), total ocular symptom score (TOSS), and visual analogue scale (VAS) score were assessed at baseline and on week 4. The primary endpoint was the effective rate after 4 weeks of INCS therapy. RESULTS In addition to the known contributing factors, one genotype of GLCCI1, namely, rs37973, was significantly associated with the INCS response (OR=0.598, 95% confidence interval: 0.41 to 0.87, P=0.007). The effective rate of the GG group was lower than those of the AA and AG groups (AA vs. GG: 73.7% vs. 51.6%, P=0.007; AG vs. GG: 78.8% vs. 51.6%, P=0.000). In addition, the TNSS, TOSS, and VAS were higher for the patients in the GG group than for those in the AA and AG groups on week 4. CONCLUSIONS The GLCCI1 rs37973 variant is a risk factor for glucocorticoid resistance in Chinese patients with SAR who receive short-term INCS treatment.