Intrinsic factors responsible for brittle versus ductile nature of refractory high-entropy alloys.

Refractory high-entropy alloys (RHEAs) are of interest for ultrahigh-temperature applications. To overcome their drawbacks - low-temperature brittleness and poor creep strength at high temperatures - improved fundamental understanding is needed. Using experiments, theory, and modeling, we investigated prototypical body-centered cubic (BCC) RHEAs, TiZrHfNbTa and VNbMoTaW. The former is compressible to 77 K, whereas the latter is not below 298 K. Hexagonal close-packed (HCP) elements in TiZrHfNbTa lower its dislocation core energy, increase lattice distortion, and lower its shear modulus relative to VNbMoTaW whose elements are all BCC. Screw dislocations dominate TiZrHfNbTa plasticity, but equal numbers of edges and screws exist in VNbTaMoW. Dislocation cores are compact in VNbTaMoW and extended in TiZrHfNbTa, and different macroscopic slip planes are activated in the two RHEAs, which we attribute to the concentration of HCP elements. Our findings demonstrate how ductility and strength can be controlled through the ratio of HCP to BCC elements in RHEAs.

Machine learning algorithms being an auxiliary tool to predict the overall survival of patients with renal cell carcinoma using the SEER database.

Background: The clinical prognosis assessment of renal cell carcinoma (RCC) still relies on nuclear grading and nuclear score by naked eye with microscope, which has defects long time, low efficiency, and uneven evaluation level criteria. There are few machine learning (ML) studies investigating the prognosis in the RCC literature which could also quantify the risk of postoperative recurrence of RCC patients and guide cancer patients to conduct individualized postoperative clinical management. This study evaluated the suitability of ML algorithms for survival prediction in patients with RCC. Methods: A total of 192,912 RCC patients from the Surveillance, Epidemiology, and End Results (SEER) were obtained from 2004 to 2015. Six ML algorithms including support vector machine (SVM), Bayesian method, decision tree, random forest, neural network, and Extreme Gradient Boosting (XGBoost) were applied to predict overall survival (OS) of RCC. Results: Patients from the SEER with a median age of 62 years and the pathological types were clear cell RCC (47.6%), papillary RCC (9.5%), chromophobe RCC (4.0%) and others (4.1%) were collected. In the deleting patients with missing data, the highest accurate model was XGBoost [area under the curve (AUC) 67.0%]. In the deleting patients with missing data and survival time <5 years, the accuracy of random forest, neural network and XGBoost were high, with AUC of 80.8%, 81.5% and 81.8%, respectively. In the only deleting the missing tumor diameter and filling the missing dataset with missForest, the highest accurate model was random forest (AUC: 71.9%). In this study, the overall accuracy of the SVM model was not high, apart from in the population of patients with deleting the missing tumor diameter and survival time <5 years, and filling the missing data with missForest. Random forest, neural network and XGBoost had high accuracy, with AUC of 84.1%, 84.7% and 84.8%, respectively. Conclusions: ML algorithms could be used to predict the prognosis of RCC. It could quantify the recurrence possibility of patients and help more individualized postoperative clinical management. Given the limitations and complexity of datasets, ML may be used as an auxiliary tool to analyze and process larger datasets and complex data.

Crustacean-inspired chitin-based flexible buffer layer with a helical cross-linked network for bamboo fiber/poly(3-hydroxybutyrate) biocomposites.

Marine biological resources, serving as a renewable and sustainable reservoir, holds significant import for the utilization of composite material. Hence, we produced bamboo fiber/poly(3-hydroxybutyrate) (BF/PHB) biocomposites with exceptional performance and economic viability, drawing inspiration from the resilience of crustacean shells. Polyaminoethyl modified chitin (PAECT) was synthesized using the alkali freeze-thaw method and introduced into the interface between BF and PHB to improve interfacial adhesion. The resulting chitin fibers, characterized by their intertwined helical chains, constructed a flexible mesh structure on the BF surface through an electrostatic self-assembly approach. The interwoven PAECT filaments infiltrated the dual-phase structure, acting as a promoter of interfacial compatibility, while the flexible chitin network provided a greater capacity for deformation accommodation. Consequently, both impact and tensile strength of the BF/PHB composites were notably enhanced. Additionally, this flexible layer ameliorated the thermal stability and crystalline properties of the composites. This investigation aimed to leverage the distinctive helical configuration of chitin to facilitate the advancement of bio-reinforced composites.

Efficient Photothermal Anti-/Deicing Enabled by 3D Cu2-x S Encapsulated Phase Change Materials Mixed Superhydrophobic Coatings.

Photothermal superhydrophobic surfaces are one of the most promising anti-/deicing materials, yet they are limited by the low energy density and intermittent nature of solar energy. Here, a coupling solution based on microencapsulated phase change materials (MPCMs) that integrates photothermal effect and phase change thermal storage is proposed. Dual-shell octahedral MPCMs with Cu2 O as the first layer and 3D Cu2-x S as the second layer for the first time is designed. By morphology and phase manipulation of the Cu2-x S shell, the local surface plasmonic heating modulation of MPCMs is realized, and the MPCM reveals full-spectrum high absorption with a photothermal conversion efficiency up to 96.1%. The phase change temperature and enthalpy remain in good consistency after 200 cycles. Multifunctional photothermal phase-change superhydrophobic composite coatings are fabricated by combining the hydrolyzed and polycondensation products of octadecyl trichlorosilane and the dual-shell MPCM. The multifunctional coatings exhibit excellent anti-/deicing performance under low temperature and high humidity conditions. This work not only provides a new approach for the design of high-performance MPCMs but also opens up an avenue for the anti-icing application of photothermal phase-change superhydrophobic composite coatings.

Clinicopathological characteristics, surgical treatments, and oncological outcomes of localized primary unifocal urothelial carcinoma involving the ureterovesical junction.

OBJECTIVE: To investigate clinicopathological characteristics, surgical treatments, and oncological outcomes of patients with localized primary unifocal urothelial carcinoma involving the ureterovesical junction (UC-UVJ). PATIENTS AND METHODS: Localized primary unifocal UC-UVJ cases in patients admitted to our hospital from March 2013 to August 2021 were reviewed. Clinicopathological parameters, perioperative data, and oncological outcomes were compared between patients grouped by tumor location and surgical treatment. RESULTS: A total of 130 patients with localized primary unifocal UC-UVJ were enrolled in this study. These included 72 cases of bladder cancer (BC) involving the ureteral orifice, and 58 cases of upper urinary tract urothelial carcinoma (UTUC) involving the intramural ureter. The proportion of male patients, hydronephrosis, flank pain/abdominal pain, and tumor size differed significantly between the BC and UTUC groups (all P < 0.05). During the median follow-up period of 32.9 months, 49 cases (37.7%) recurred and 29 (22.3%) died from urothelial carcinoma (UC), though no statistical difference in recurrence (P = 0.436) or cancer-specific mortality (P = 0.653) was observed between the BC and UTUC groups. Cox proportional hazards regression analysis identified age, tumor grade, and lymphovascular invasion (LVI) as independent predictors of cancer-specific survival (CSS), and sex, T stage, tumor grade, and LVI as independent predictors of recurrence-free survival (RFS). CONCLUSION: Owing to positional properties, patients with localized primary unifocal UC-UVJ exhibited significant heterogeneity, leading to varied treatment strategies. No statistically significant differences in CSS or RFS were observed between the BC and UTUC groups. Furthermore, age, sex, T stage, tumor grade, and LVI should be carefully considered in clinical practice because of their associations with CSS and RFS.

Electron transport chain and mTOR inhibition synergistically decrease CD40 signaling and counteract venetoclax resistance in chronic lymphocytic leukemia.

CD40 signaling upregulates BCL-XL and MCL-1 expression in the chronic lymphocytic leukemia (CLL) lymph node microenvironment, affording resistance to the BCL-2 inhibitor, venetoclax. Venetoclax resistance in the therapeutic setting and after long-term laboratory selection has been linked to metabolic alterations, but the underlying mechanism(s) are unknown. We aimed here to discover how CD40 stimulation as a model for tumor microenvironment-mediated metabolic changes, affects venetoclax sensitivity/resistance. CD40 stimulation increased oxidative phosphorylation and glycolysis, but only inhibition of oxidative phosphorylation countered venetoclax resistance. Furthermore, blocking mitochondrial import of pyruvate, glutamine or fatty acids affected CLL metabolism, but did not prevent CD40-mediated resistance to venetoclax. In contrast, inhibition of the electron transport chain (ETC) at complex I, III or V attenuated CLL activation and ATP production, and downregulated MCL-1 and BCL-XL, correlating with reduced CD40 surface expression. Moreover, ETC inhibition equaled mTOR1/2 but not mTOR1 inhibition alone for venetoclax resistance, and all three pathways were linked to control of general protein translation. In line with this, ETC plus mTOR inhibition synergistically counteracted venetoclax resistance. These findings link oxidative CLL metabolism to CD40 expression and cellular signaling, and may hold clinical potential.

Changes of Temporomandibular Joint Morphology and Symptoms in Class II Malocclusion Patients With Bilateral Sagittal Split Ramous Osteotomy.

This study included 46 patients with class II malocclusion ranging in age from 19 to 39 years old treated with bilateral sagittal split ramous osteotomy (BSSRO). Left and right temporomandibular joints (TMJs) of each subject were evaluated independently with cone-beam computed tomography (CBCT) before operation (T1), 1 week after operation (T2), and 1 year after operation (T3) and assessed the effects of orthognathic surgery (OGS) on the temporomandibular joint disease (TMD) symptoms. Temporomandibular joint morphology evaluation included condylar volume, condylar area, cortical bone thickness, depth of the mandibular fossa, fossa thickness, joint nodule angle, joint space, and condyle-fossa relationship, which were calculated by using the Mimics software and 3-matic software. Data were statistically analyzed with SPSS software (P <0.05 means statistically significant). In our study, bilateral TMJs have no difference in T3. Bilateral sagittal split ramous osteotomy had no significant effect on the articular fossa. The condyle volume and surface area decreased from T1 to T3, but the cortical thickness of the bone did not change significantly. More anterior condyle positions in T1 and more posterior in T3.21 patients had at least 1 sign or symptom of TMD in T1 and 27 patients in T3. Four patients who were asymptomatic in T1 developed pain after surgery, 10 developed noises, 12 showed limited mouth opening, and 8 had abnormal opening patterns. It is concluded that more condylar posterior position after BSSRO and the reduction of condyle may be related to the enlargement of anterior space. The number of patients with joint symptoms increased postoperative, and the impact of BSSRO on TMD may be negative.

Pathogenicity virulence of Beauveria spp. and biosafety of the BbMQ strain on adult ectoparasitic beetles, Dastarcus helophoroides Fairmaire (Coleoptera: Colydiidae).

Introduction: Beauveria spp. and Dastarcus helophoroides Fairmaire adults were simultaneously released to attack elder larvae or pupae of Monochamus alternatus in pine forests in China. However, little is known about the pathogenicity virulence and biosafety of Beauveria spp. on beneficial adults of D. helophoroides, and specific Beauveria bassiana (Bb) strains should be selected for synthetic release together with D. helophoroides. Methods: A total of 17 strains of Beauveria spp. were collected, isolated, and purified, and then their mortality, cadaver rate, LT50, spore production, spore germination rate, and growth rate of D. helophoroide adults were calculated based on 0-20 days data after spore suspension and powder contact. Results and discussion: The lethality rate of BbMQ, BbFD, and BbMH-03 strains to D. helophoroides exceeded 50%, and the cadaver rate reached 70.6%, among which the mortality rate (82.22%), cadaver rate (47.78%), spore production (1.32 × 109 spores/ml), spore germination rate (94.71%), colony dimension (49.15 mm2), and LT50 (10.62 d) of the BbMQ strain were significantly higher than those of other strains (P < 0.01), and the mortality of D. helophoroides adults increased significantly with increased spore suspension concentration, with the highest mortality reaching 92.22%. This strain was identified as Beauveria bassiana by morphological and molecular methods, while the BbWYS strain had a minimum lethality of only 5.56%, which was safer compared to other strains of adult D. helophoroide. Consequently, the biological characteristics and pathogenicity of different Beauveria bassiana strains varied significantly in their effects on D. helophoroide adults, and the safety of different strains should be assessed when they are released or sprayed to control multiple pests in the forest. The BbMQ strain should not be simultaneously sprayed with releasing D. helophoroide adults in the same forest, while the BbWYS strain can be used in concert with D. helophoroide to synergize their effect.

Mussel-inspired laccase-mediated polydopamine graft onto bamboo fibers and its improvement effect on poly(3-hydroxybutyrate) based biocomposite.

Bamboo fiber (BF) reinforced polyhydroxybutyrate (PHB) has become popular in developing an eco-friendly and sustainable biocomposite, while the weak interfacial compatibility between them is a major problem to overcome. This work, inspired by mussel super adhesion, creates a facile, highly efficient, and environmentally friendly solution based on in situ laccase-catalysed dopamine polymerization under a naturally acidic environment. The result indicates that a stabilized polydopamine coating is successfully grafted onto the lignin of BF, and it also enhances the thermal stability of the BF and biocomposite. Furthermore, modification of BF via laccase-catalysed polydopamine is superior to the conventional method of polydopamine under alkaline condition, and has outstanding advantages in terms of BF integrity protection. The optimal composition of biocomposite with BF treated by polydopamine under 1 U/mL concentration of laccase shows improvement in the impact strength, tensile strength, tensile modulus, bending strength, and modulus of elastic by 33.85 %, 9.27 %, 31.74 %, 11.76 %, and 12.92 %, respectively, compared to the unmodified counterpart. This work provides an insightful understanding of the mechanism and benefits of laccase-catalysed polydopamine modification of BF in a natural environment. It contributes to the efficient and environmentally friendly utilization of polydopamine for fabricating high-performance lignocellulosic fiber reinforced biocomposites.

AC-Bipolar Electropolymerization of 3,4-Ethylenedioxythiophene in Ionic Liquids.

Recently, alternating current (AC)-bipolar electropolymerization of 3,4-ethylenedioxythiophene (EDOT) has been reported to produce poly(3,4-ethylenedioxythiophene) (PEDOT) fibers from the terminals of bipolar electrodes in acetonitrile solution (MeCN) containing low concentrations of supporting salts in a template-free manner. Here, we extend such methodology in ionic liquid (IL) media. Three kinds of ILs, diethylmethyl(2-methoxyethyl)ammonium tetrafluoroborate ([DEME][BF4]), 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]), and diethylmethyl(2-methoxyethyl)ammonium bis(trifluoromethylsulfonyl)imide ([DEME][TFSI]), with different electric field transmission efficiencies and diffusion coefficients were employed as solvents for the AC-bipolar electropolymerization of EDOT. A variety of PEDOT morphologies were obtained in these three ILs, showing a relationship with the physicochemical properties of the ILs. We successfully confirmed the growth of PEDOT fibers in ILs and systematically discussed the factors that influenced their growth.

Cryo-EM structures of human SPCA1a reveal the mechanism of Ca2+/Mn2+ transport into the Golgi apparatus.

Secretory pathway Ca2+/Mn2+ ATPase 1 (SPCA1) actively transports cytosolic Ca2+ and Mn2+ into the Golgi lumen, playing a crucial role in cellular calcium and manganese homeostasis. Detrimental mutations of the ATP2C1 gene encoding SPCA1 cause Hailey-Hailey disease. Here, using nanobody/megabody technologies, we determined cryo-electron microscopy structures of human SPCA1a in the ATP and Ca2+/Mn2+-bound (E1-ATP) state and the metal-free phosphorylated (E2P) state at 3.1- to 3.3-Å resolutions. The structures revealed that Ca2+ and Mn2+ share the same metal ion-binding pocket with similar but notably different coordination geometries in the transmembrane domain, corresponding to the second Ca2+-binding site in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). In the E1-ATP to E2P transition, SPCA1a undergoes similar domain rearrangements to those of SERCA. Meanwhile, SPCA1a shows larger conformational and positional flexibility of the second and sixth transmembrane helices, possibly explaining its wider metal ion specificity. These structural findings illuminate the unique mechanisms of SPCA1a-mediated Ca2+/Mn2+ transport.

Energy Utilization and Flight Muscle Development in Chrysoperla sinica (Neuroptera: Chrysopidae) Female Adults: Relationship With Age and Flight Behavior.

We investigated the accumulation of energy substances, dynamics of flight muscle development, changes in energy substances accumulation, and flight muscle structure after flight activities in female adults of the green lacewing Chrysoperla sinica (Tjeder), a common natural enemy of various insect pests in China. Virgin individuals were chosen at 24, 72, and 120 h after eclosion for energy substance determination and flight muscle observation in this study. Individuals with strong flight ability at 72 h after eclosion were selected for tethered flight assays, followed by detection of energy substances, and flight muscle observation. The results showed that virgin female adults had the highest fat content 72 h after eclosion. Sarcomere length and myofibril diameter changed significantly with age, with the lowest at 24 h after eclosion. With an increase in flight distance, the fat and glycogen contents, sarcomere length, and volume fraction of the transverse tubular system (T-system) decreased and myofibril diameters increased. The volume fraction of the mitochondria did not significantly change, but the structure of the mitochondrial membrane was destroyed, inclusions were reduced, and cavities appeared. The reserves of energy substances, especially lipids, are closely related to the flight ability of C. sinica. The observational results of both flight muscle structure and morphology of mitochondria build a strong relationship with flight behavior. This research should help reveal the regulatory mechanism of flight activity of C. sinica.

Pan-Cancer Analysis of the TRP Family, Especially TRPV4 and TRPC4, and Its Expression Correlated with Prognosis, Tumor Microenvironment, and Treatment Sensitivity.

BACKGROUND: Transient receptor potential (TRP) channels are involved in various physiological, pathological, and tumorigenesis-related processes. However, only a few studies have comprehensively analyzed TRP family members and their association with prognosis and tumor microenvironment (TME) in various cancers. Thus, in this study, we focused on TRP channels in pan-cancer and screened two typical TRP channels, TRPV4 and TRPC4, as examples. METHODS: Based on the latest public databases, we evaluated the expression level and prognostic value of TRP family genes in pan-cancer tissues via various bioinformatic analytical methods, and investigated the relationship between the expression of TRP family genes with TME, stemness score, immune subtype, drug sensitivity, and immunotherapy outcome in pan-cancer tissues. RESULTS: Pan-cancer analysis revealed that the TRP family genes were differentially expressed in tumor and para-carcinoma tissues. A significant correlation existed between the expression of TRP family genes and prognosis. The expression of TRP family genes was significantly correlated with stromal, immune, RNA stemness, and DNA stemness scores in pan-cancer tissues. Our results indicated that the expression of TRP family genes correlated with the sensitivity to various drugs including PLX-4720, SB-590885, and HYPOTHEMYCIN, immunotherapy outcome, and immune-activation-related genes. Immunohistochemical analysis revealed significant differential expression of TRPV4 in bladder and para-carcinoma tissues. CONCLUSIONS: Our study elucidated the possible role of TRP family genes in cancer progression and provided insights for further studies on TRP family genes as potential pan-cancer targets to develop diagnostic and therapeutic strategies.

The Combination of Chrysin and Cisplatin Induces Apoptosis in HepG2 through Down-regulation of cFLIP and Activity of Caspase.

AIM: The study aims to investigate the combined effects of chrysin and cisplatin on hepatoma(HepG2) cell lines in vivo and in vitro. OBJECTIVE: Studies have suggested that chrysin can enhance the sensitivity of tumor cells to apoptosis. Drug resistance in tumor cells reduced the effectiveness of chemotherapy drugs such as cisplatin. We investigated whether the combination of chrysin and cisplatin can induce more apoptosis than chrysin alone and cisplatin alone. METHODS: HepG2 cells were pretreated with chrysin for 2 h, followed by the addition of cisplatin for another 24 h. The morphologic changes were observed under inverted microscope and the cell viability was measured using the MTT test. The protein and cleavage of caspase-3,8,9, PARP, and cFLIP were determined by Western blotting. RESULTS: The cell viability of the HepG2 cell can be reduced by the combination of chrysin pretreatment for 2 h and cisplatin addition for 24 h; Caspase-3,8,9 and PARP were cleaved after 12 h treatment with chrysin and cisplatin; Pancaspase inhibitor, Z-VAD-fmk, could reverse the apoptosis induced by chrysin and cisplatin in HepG2 cells; cFLIP was down-regulated by the combination of chrysin and cisplatin, and could be reversed by Z-VAD-fmk; the xenografted HepG2 cells formed a tumor in one week; At the end of the experiment, there were significant differences in relative tumor volume (RTV) and relative tumor proliferation rate between the combined group and the control group, the chrysin group and the cisplatin group; Western blotting showed that the levels of PARP, cFLIP, and caspase-3 proteins in isolated tumor tissues also decreased under the combined action of chrysin and cisplatin. CONCLUSION: The combination of chrysin and cisplatin induces apoptosis of hepatic tumor in vivo and in vitro. It downregulates cFLIP and then activates caspase-8, which triggers caspase-mediated apoptosis of HepG2 cell.

Numerical modeling and field test of sonic crystal acoustic barriers.

The rapid development of highway traffic has gradually deteriorated the acoustic environment along the line. Sonic crystal theory provides new ideas for traffic acoustic barrier. However, the lack of practical numerical models and field test verifications has restricted the promotion and application of sonic crystal acoustic barriers (SCABs). In this study, a field test was conducted to study the noise reduction performance of SCAB. The SCAB exhibits excellent wave attenuation in the band gap, when compared with concrete acoustic barriers (CABs) along highways, the noise reduction performance in the band gap is improved by 0.5-2.1 dB(A), especially at the local peak in the highway noise spectrum. However, from the perspective of total insertion loss, CAB performs better than SCAB in all distances in the protected area. Next, the 3D FEM model is established based on the highway site and validated by the measured results. Compared with the commonly used 2D model, the 3D FEM model is more practical for considering the top diffraction and ground reflection, which influence the noise reduction performance a lot and need to be considered. To improve the noise reduction performance of SCAB, three types of optimization measures are explored. The gradient combination of scatterers can effectively improve the noise reduction effect in the low-frequency band gap, especially the high- to low-gradient layout. Besides, not only the porous sound-absorbing material but also the microperforated plates can improve the noise reduction effect, especially outside the band gap. The larger perforation rates and smaller apertures of microperforated plate are preferred in SCAB. This work provides field test support and promotes the application of SCABs in traffic noise control.

High-Throughput Electrosynthesis of Gradient Polypyrrole Film Using a Single-Electrode Electrochemical System.

As an effective approach for materials synthesis, bipolar electrochemistry has been earning a renewed interest nowadays thanks to its unique features compared to conventional electrochemistry. Indeed, the wireless mode of electrode reactions and the generation of a gradient potential distribution above the bipolar electrode are among the most appealing qualities of bipolar electrochemistry. In particular, the gradient potential distribution is a highly attractive characteristic for the fabrication of surfaces with gradients in their chemical properties or molecular functionalities. Herein, we report the high-throughput electrosynthesis of gradient polypyrrole films by means of a new electrochemical cell design named the single-electrode electrochemical system (SEES). SEESs are made by attaching an inert plastic board with holes onto an indium tin oxide electrode, constructing multiple microelectrochemical cells on the same electrode. This type of arrangement enables parallel electrochemical reactions to be carried out simultaneously and controlled in a contactless manner by a single electrode. Several experimental conditions for polypyrrole film growth were extensively investigated. Furthermore, the gradient property of the polymer films was evaluated by thickness determination, surface morphology analysis, and contact angle measurements. The use of SEES has been demonstrated as a convenient and cost-effective strategy for high-throughput electrosynthesis and electroanalytical applications and has opened up a new door for gradient film preparation via a rapid condition screening process.

Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity.

Cellular senescence involves a stable cell-cycle arrest coupled to a secretory program that, in some instances, stimulates the immune clearance of senescent cells. Using an immune-competent liver cancer model in which senescence triggers CD8 T cell-mediated tumor rejection, we show that senescence also remodels the cell-surface proteome to alter how tumor cells sense environmental factors, as exemplified by type II interferon (IFNγ). Compared with proliferating cells, senescent cells upregulate the IFNγ receptor, become hypersensitized to microenvironmental IFNγ, and more robustly induce the antigen-presenting machinery-effects also recapitulated in human tumor cells undergoing therapy-induced senescence. Disruption of IFNγ sensing in senescent cells blunts their immune-mediated clearance without disabling the senescence state or its characteristic secretory program. Our results demonstrate that senescent cells have an enhanced ability to both send and receive environmental signals and imply that each process is required for their effective immune surveillance. SIGNIFICANCE: Our work uncovers an interplay between tissue remodeling and tissue-sensing programs that can be engaged by senescence in advanced cancers to render tumor cells more visible to the adaptive immune system. This new facet of senescence establishes reciprocal heterotypic signaling interactions that can be induced therapeutically to enhance antitumor immunity. See related article by Marin et al., p. 410. This article is highlighted in the In This Issue feature, p. 247.

The association between serum cadmium and diabetes in the general population: A cross-sectional study from NHANES (1999-2020).

Background: Associations between serum cadmium and diabetes had been reported in previous studies, however there was still considerable controversy regarding associations. Studies in general population that investigated the effects of serum cadmium on diabetes were currently lacking. We designed this cross-sectional study among U.S. adults under high and low cadmium exposure to assess associations between serum cadmium and diabetes. Methods: This cross-sectional study analyzed 52,593 adults who aged more than 20 years and participated in the National Health and Nutrition Examination Survey (NHANES), 1999-2020. The missing values and extreme values in the covariables were filled by multiple interpolation. Univariate logistics regression, multivariate logistics regression and smooth fitting curves were used to analyze the association between serum cadmium and diabetes. Simultaneously, sensitivity analysis was carried out by converting the serum cadmium from continuous variable to categorical variable. The stratification logistics regression model was used to analyze whether there were special groups in each subgroup to test the stability of the results. Results: In this cross-sectional study, serum cadmium levels were negatively correlated with the occurrence of diabetes in the low serum cadmium exposure group (OR = 0.811, 95% CI 0.698, 0.943; P = 0.007). There was no association between serum cadmium level and the occurrence of diabetes in the high serum cadmium exposure group (OR = 1.01, 95% CI 0.982, 1.037; P = 0.511). These results were consistent across all the subgroups (P for interaction >0.05). Conclusion: Serum cadmium was negatively associated diabetes among the representative samples of the whole population in the United States under the normal level of serum cadmium exposure. However, there was no association between serum cadmium level and the occurrence of diabetes in the high serum cadmium exposure group. This study promoted an update of new preventative strategy targeting environment for the prevention and control of diabetes in the future.

Integrated Analysis of the Fecal Metagenome and Metabolome in Bladder Cancer in a Chinese Population.

Bladder cancer (BLCA) is a common malignancy of the urinary system. The gut microbiome produces various metabolites that play functional roles in tumorigenesis and tumor progression. However, the integrative analysis of the gut microbiome and metabolome in BLCA has still been lacking. Thus, the aim of this study was to identify microbial and functional characteristics and metabolites in BLCA in a Chinese population. Metagenomics, targeted metabolomics, bioinformatics, and integrative analysis were used in fecal samples of BLCA patients and healthy individuals. We found gut microbiomes were significantly dysregulated in BLCA patients, including Bifidobacterium, Lactobacillus, Streptococcus, Blautia, and Eubacterium. We also found 11Z-eicosenoic acid, 3-methoxytyrosine, abrine, aniline-2-sulfonate, arachidic acid, conjugated linoleic acids, elaidic acid, glycylleucine, glycylproline, leucyl-glycine, linoelaidic acid, linoleic acid, nicotinamide hypoxanthine dinucleotide, oleic acid, petroselinic acid, and ricinoleic acid to be significantly decreased, while cholesterol sulfate was significantly increased in BLCA patients. Integration of metagenomics and metabolomics revealed interactions between gut microbiota and metabolites and the host. We identified the alterations of gut microbiomes and metabolites in BLCA in a Chinese population. Moreover, we preliminarily revealed the associations between specific gut microbiomes and metabolites. These findings determined potential causative links among gut dysbiosis, dysregulated metabolites, and BLCA.

Prognosis Risk Model Based on Necroptosis-Related Signature for Bladder Cancer.

BACKGROUND: Bladder cancer(BLCA) is the ninth most common cancer. In recent years, necroptosis was found to be related to the occurrence and development of tumors. In this study, we aimed to construct a model based on a necroptosis-related signature to evaluate the potential prognostic application in BLCA. METHODS: A total of 67 necroptosis-related genes were used to select the ideal cluster numbers, and it was found that there were four necroptosis-related patterns. Then, we compared the gene expression levels among all of the groups and established a necroptosis-related prognostic model. We made the following enrichment analysis of function and built a novel scoring system, the NEC score, to evaluate the state of necroptosis according to the expression level of necroptosis-related genes. RESULTS: A total of 67 necroptosis-related genes were used to define four distinct necroptosis-related patterns: NEC cluster1-4. Each NEC cluster exhibited different patterns of survival and immune infiltration. Based on univariate Cox regression analyses and least absolute shrinkage and selection operator (Lasso) regression, 14 necroptosis-related genes were established to develop the NEC score. Patients were divided into two groups based on the NEC score. Patients in the high NEC score group had a significantly poorer overall survival than those in the low NEC score group. We further confirmed the correlation of clinical characteristics, as well as the immunotherapy outcome, with the NEC score, and confirmed the potential of the NEC score to be an independent prognostic factor. Furthermore, we compared the expression levels of eight potential biomarker genes between our own BLCA tissues and para-carcinoma tissue. CONCLUSION: We developed a novel NEC score that has a potential prognostic value in BLCA patients and may help personalized immunotherapy counselling.