Cyclic (Alkyl)(Amino)Carbene-Iminoboryl Compounds with Three Formal Oxidation States.

BN/CC isosterism is an effective strategy to build hybrid functional molecules with unique properties. In contrast to the alkynyl iminium salts derived from cyclic (alkyl)(amino)carbenes (CAACs) that feature only one reversible reduction wave, the isoelectronic cationic CAAC-iminoboryl adducts could be singly and doubly reduced smoothly. Both the resultant neutral radical and anionic azaborataallenes bear NBC-mixed allenic structures. The former radical has a high spin-density of 0.55e at CCAAC carbon, yet exhibits formal boron-centered radical reactivity. The latter azaborataallenes feature the nucleophilic CCAAC center and polar N(δ-)═B(δ+)═C(δ-) unit, and readily undergo nucleophilic substitution, isocyanide insertion, dipolar addition and cycloaddition reactions etc. The N-substituents have been shown to have a significant influence on the solid-state structure, thermal stability, and reactivity of azaborataallenes. This work showcases the allenic BN-unsaturated species as versatile building blocks in organic synthesis.

Isolable T-Shaped Planar Silyl Anion.

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.

Aromatic 1,4,2,3-Diazadiborole Featuring an Unsymmetrical B=B Entity: A Versatile Synthon for Unusual Boron Heterocycles.

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.

Let-7b-5p inhibits colon cancer progression by prohibiting APC ubiquitination degradation and the Wnt pathway by targeting NKD1.

Naked cuticle homolog 1 (NKD1), which is expressed at low levels in many tumors, is considered an inhibitor of the Wnt/ß-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 ß-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-ß-catenin signaling pathway inhibited colon cancer cell progression.

Clinical pathology of primary central nervous system lymphoma in HIV-positive patients-a 41 Chinese patients retrospective study.

OBJECTIVES: The purpose of this study was to investigate the clinicopathological characteristics of primary central nervous system lymphoma (PCNSL). METHODS: We collected 41 PCNSL formalin-fixed, paraffin-embedded (FFPE) samples from human immunodeficiency virus (HIV)-positive patients and performed HE (haematoxylin-eosin) staining, immunohistochemistry (IHC) staining, in situ hybridization, fluorescence in situ hybridization (FISH). Real-time quantitative polymerase chain reaction (RT-qPCR) was performed in 9 cases of FFPE samples. Meanwhile, we analysed the clinical pathological significance of the results. RESULTS: Seven patients had diffuse large B-cell lymphoma (DLBCL) with germinal centre B-cell (GCB)-like DLBCL, 32 had activated B-cell (ABC)-like DLBCL, and 2 had Burkitt lymphoma (BL). GCB-like DLBCL patients were older at onset (P = 0.040).A lower CD4+ T-cell count and a decrease in cerebrospinal fluid (CSF) glucose content were more frequent in ABC-like DLBCL (P = 0.012, P = 0.006). Overexpression of P53 was more in ABC-like DLBCL (P = 0.041). 73.2 % cases were Epstein-Barr encoding region (EBER) positive, which was more likely in ABC-like DLBCL patients (P = 0.037). EBV DNA were detected in 5/7 EBER-negative DLBCL cases and none (0/2) of the BL cases. All the cases were negative for HHV8 staining. None of the 7 Double expressor lymphoma (DEL) cases had BCL2, BCL6, or c-MYC genetic rearrangements. CONCLUSIONS: HIV-related PCNSL showed unique clinical pathological significance. None of EBV detected in HIV-related BL and without HHV8 infectious are new sights in our single-center study of Chinese HIV-related PCNSL patients.

Asprosin is positively associated with metabolic syndrome in hemodialysis patients: a cross-sectional study.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: Fasting serum asprosin is positively correlated with MS and could be an independent risk factor for MS in hemodialysis patients.

Geometrically Constrained Organoboron Species as Lewis Superacids and Organic Superbases.

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(C6 F5 )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 Et3 SiH 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.

Acid/Base-Free Acyclic Anionic Oxoborane and Iminoborane Bearing Diboryl Groups.

Anionic oxoboranes and neutral iminoboranes, which are isoelectronic to ketones and alkynes, respectively, have attracted much attention because of their unique structures and various reactivity. However, acid/base-free oxoboranes and iminoboranes are still limited, and readily accessible examples with diverse electronic and steric characteristics are highly desirable. Herein, we report the first syntheses of the acyclic anionic oxoborane 2 and iminoborane 4 bearing two boryl ligands, both of which are acid/base-free. Spectroscopic analysis, X-ray crystallography, and theoretical calculations reveal that 2 and 4 possess a polarized terminal B═O double bond and central B≡N triple bond, respectively.

ABCB1 gene polymorphisms impact the effect of high-dose intravenous methylprednisolone therapy on optic neuritis associated with AQP4-IgG-positive neuromyelitis optica spectrum disorder.

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.

Glucocorticoid-Induced Transcription Factor 1 (GLCCI1) Variant Impacts the Short-Term Response to Intranasal Corticosteroids in Chinese Han Patients with Seasonal Allergic Rhinitis.

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.

Unveiling the regulatory mechanism of nimotuzumab on PD-L1 expression in head and neck squamous cell carcinoma patients: Implications for enhanced anticancer treatment strategies.

The overexpression of programmed death ligand 1 (PD-L1) is associated with resistance to anticancer therapies and poor prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Nimotuzumab, a humanized anti-epidermal growth factor receptor (EGFR) mAb, has been widely used clinically for treating several solid tumors. However, whether its anticancer effect involves a reduction in PD-L1 expression remains unclear. The current study aimed to investigate the regulatory effects and underlying mechanism of nimotuzumab on PD-L1 expression in HNSCC both in vitro and in vivo. In vitro, nimotuzumab inhibited IFN-γ-induced PD-L1 upregulation at both the transcriptional and protein levels in the HNSCC cell lines. Subsequent mechanism research revealed that nimotuzumab suppressed IFN-γ-stimulated PD-L1 upregulation mainly by inhibiting phosphorylation of EGFR/MEK/ERK pathway, which was further validated by MEK and ERK inhibitors. In a HNSCC tumor-bearing model, nimotuzumab significantly decreased PD-L1 expression during tumor progression or chemotherapy, and this reduction was accompanied by increased sensitivity of the tumor to docetaxel and atezolizumab. Additionally, nimotuzumab reversed PD-L1 upregulation when combined with Taxol + Cisplatin (TP) induction chemotherapy regimens and improved the CD4+ and CD8+ T cells infiltration in HNSCC patients. These findings provide new insights into the anticancer mechanisms of nimotuzumab in HNSCC.

Extrachromosomal circular DNA (eccDNA) characteristics in the bile and plasma of advanced perihilar cholangiocarcinoma patients and the construction of an eccDNA-related gene prognosis model.

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/ß-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.

First-in-human study on pharmacokinetics, safety, and tolerability of single and multiple escalating doses of PA9159 nasal spray, a highly potent glucocorticoid in healthy Chinese volunteers.

OBJECTIVE: PA9159 (previously named VSG159) is a structurally novel and highly potent glucocorticoid that plays a role in the late development of autoimmune and inflammatory diseases. The current first-in-human ascending-dose study of the PA9159 nasal spray was conducted in healthy Chinese volunteers to evaluate its pharmacokinetics, safety, and tolerability. In addition, the effects of PA9159 on serum cortisol secretion were investigated. METHODS: This was a double-blinded, randomized, placebo-controlled clinical study that included four single-dose groups in the single ascending dose cohort (SAD) and two multiple-dose groups in the multiple ascending dose cohort (MAD), with dose ranges of 10-80 µg and 20-40 µg, respectively. PA9159 was administered bilaterally via nasal spray once only or once daily for seven days. Pharmacokinetic, safety, and tolerability profiles were evaluated. RESULTS: A total of 60 participants completed the study. PA9159 doses of up to 80 µg in the SAD and up to 40 µg in the MAD were shown to be safe and tolerable. The most common treatment-related AEs were mild and transient local nasal AEs. Morning serum cortisol levels approximately remained unchanged in both the single-dose and multiple-dose groups. PA9159 was quantified in 41.8 % (368/880) of the samples in all treatment groups, including 25.2 % (105/416) of the SAD and 56.7 % (263/464) of the MAD. The majority (>80.0 %) of PA9159 plasma concentrations ranged from 0.5 to 2 pg/mL in determined samples. The mean AUC0-t of PA9159 in the SAD was 0.91, 1.39±0.68, 11.40±9.91, and 46.30±25.80 h*pg/mL in the 10 to 80 ug single group. The mean terminal half-life time (t1/2) was 8.43 h and 8.97±2.28 h in 40 ug and 80 ug single group, respectively. The mean AUCss of PA9159 in the MAD was 31.70±7.04, 44.20±20.60 h*pg /mL, and the t1/2 was 16.00±4.18 h, 21.20±10.20 h in the 20 ug and 40 ug multiple groups, respectively. The median Tmax was approximately 6 h in both the SAD and MAD cohorts. CONCLUSIONS: The PA9159 nasal spray was generally safe and well tolerated, and the effects of PA9159 on serum cortisol levels were limited. The plasma concentration and systemic exposure to PA9159 were very low. These findings support the necessity for further clinical studies on PA9159 nasal spray in patients suffering from allergic rhinitis.

Crystalline heaviest pnictogen-dipyrromethenes: isolation, characterization, and reactivity.

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.

Vitamin D receptor gene polymorphisms are associated with the risk and features of myasthenia gravis in the Han Chinese population.

Vitamin D receptor gene (VDR) polymorphisms are candidate genetic variants for susceptibility to autoimmune diseases. Here, we explored the association between VDR polymorphisms and myasthenia gravis (MG) susceptibility and disease features in a Han Chinese population. A total of 151 patients with MG and 146 healthy controls were genotyped for VDR rs1544410, rs2228570, rs731236, and rs7975232 polymorphisms using the improved multiple ligase detection reaction. Information regarding age at onset, acetylcholine receptor (AChR-Ab) and muscle-specific kinase (MuSK-Ab) antibody status, thymus status, involved muscles at onset, and Osserman type at maximum worsening during 2-year follow-up was obtained and used for subclassification grouping. Intergroup comparisons of allele and genotype frequencies and haplotype distributions were performed between the MG and control groups and between each pair of MG subgroups. The VDR rs7975232 polymorphism was associated with the risk of MG in allele, codominant (CC vs. CA), and dominant models (p = 0.040, p = 0.018, and p = 0.018, respectively). Moreover, subjects with the ACC haplotype (order of rs731236, rs7975232, rs1544410) were more likely to develop MG than those with other haplotypes (OR = 1.486, 95% CI: 1.017-2.171, p = 0.040). In a dominant model, the rs7975232 CC genotype frequency was significantly higher in the ocular MG group than in the generalized MG group (p = 0.019). The study findings suggest that the VDR rs7975232 C allele and the ACC haplotype can be associated to an increased susceptibility to the development of MG. Trial registration: NCT05380128.

Multiple stable redox states and tunable ground states via the marriage of viologens and Chichibabin's hydrocarbon.

Chichibabin's hydrocarbon and viologens are among the most famous diradicaloids and organic redox systems, respectively. However, each has its own disadvantages: the instability of the former and its charged species, and the closed-shell nature of the neutral species derived from the latter, respectively. Herein, we report that terminal borylation and central distortion of 4,4'-bipyridine allow us to readily isolate the first bis-BN-based analogues (1 and 2) of Chichibabin's hydrocarbon with three stable redox states and tunable ground states. Electrochemically, both compounds exhibit two reversible oxidation processes with wide redox ranges. One- and two-electron chemical oxidations of 1 afford the crystalline radical cation 1˙+ and dication 12+, respectively. Moreover, the ground states of 1 and 2 are tunable with 1 as a closed-shell singlet and the tetramethyl-substituted 2 as an open-shell singlet, the latter of which could be thermally excited to its triplet state because of the small singlet-triplet gap.

A Bioequivalence Study With Pharmacokinetic Endpoints for Azithromycin Eye Drops.

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.

A crystalline T-shaped planar group 14 anion.

Isolable T-shaped planar pnictogen compounds R3Pn were reported more than three decades ago and have been attracting burgeoning interest in recent years; T-shaped planar group 14 anions, isoelectronic to R3Pn, however, are still unknown. Herein, we report the synthesis, full characterization, and reactivity of the first crystalline T-shaped planar group 14 anion 4 bearing a trinitrogen pincer ligand. DFT calculations indicate that the tricoordinate germanium center features both an unoccupied 4p orbital and two lone pairs of electrons. Its electron-rich nature allows for the nucleophilic attack on the methyl iodine giving methyl-substituted complex 5 and facile oxidation of the germanium center by elemental sulfur and selenium to furnish unpresented organic anions bearing terminal Ge[double bond, length as m-dash]Ch (Ch = S or Se) double bonds.

Identification and validation of a new pyroptosis-associated lncRNA signature to predict survival outcomes, immunological responses and drug sensitivity in patients with gastric cancer.

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.

Effect of Low Temperature on Insecticidal Protein Contents of Cotton (Gossypium herbaceum L.) in the Boll Shell and Its Physiological Mechanism.

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.