Identifying and evaluating a disulfidptosis-related gene signature to predict prognosis in colorectal adenocarcinoma patients.

Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung adenocarcinoma, and hepatocellular carcinoma. However, its role in colon adenocarcinoma (COAD) has been infrequently discussed. In this study, we developed and validated a prognostic model based on 20 disulfidptosis-related genes (DRGs) using LASSO and Cox regression analyses. The robustness and practicality of this model were assessed via a nomogram. Subsequent correlation and enrichment analysis revealed a relationship between the risk score, several critical cancer-related biological processes, immune cell infiltration, and the expression of oncogenes and cell senescence-related genes. POU4F1, a significant component of our model, might function as an oncogene due to its upregulation in COAD tumors and its positive correlation with oncogene expression. In vitro assays demonstrated that POU4F1 knockdown noticeably decreased cell proliferation and migration but increased cell senescence in COAD cells. We further investigated the regulatory role of the DRG in disulfidptosis by culturing cells in a glucose-deprived medium. In summary, our research revealed and confirmed a DRG-based risk prediction model for COAD patients and verified the role of POU4F1 in promoting cell proliferation, migration, and disulfidptosis.

Control of Fusarium Head Blight of Wheat with Bacillus velezensis E2 and Potential Mechanisms of Action.

Wheat plants are impacted by Fusarium head blight (FHB) infection, which poses a huge threat to wheat growth, development, storage and food safety. In this study, a fungal strain was isolated from diseased wheat plants and identified as Fusarium asiaticum F1, known to be a member of the Fusarium graminearum species complex, agents causally responsible for FHB. In order to control this disease, new alternatives need to be developed for the use of antagonistic bacteria. Bacillus velezensis E2 (B. velezensis E2), isolated from a previous investigation in our laboratory, showed a notable inhibitory effect on F. asiaticum F1 growth and deoxynivalenol (DON) synthesis in grains. The spore germination of F. asiaticum F1 was significantly reduced and the spores showed vesicular structures when treated with B. velezensis E2. Observations using scanning electron microscopy (SEM) showed that the hyphae of F. asiaticum F1 were shrunken and broken when treated with B. velezensis E2. The RNA-seq results of F1 hyphae treated with B. velezensis E2 showed that differentially expressed genes (DEGs), which were involved in multiple metabolic pathways such as toxin synthesis, autophagy process and glycan synthesis, especially the genes associated with DON synthesis, were significantly downregulated. In summary, those results showed that B. velezensis E2 could inhibit F. asiaticum F1 growth and reduce the gene expression of DON synthesis caused by F1. This study provides new insights and antagonistic mechanisms for the biological control of FHB during wheat growth, development and storage.

Efficacy and safety of drug-coated balloons in chronic total coronary occlusion recanalization: a systematic review and meta-analysis.

BACKGROUND: With advancements in chronic total coronary occlusion (CTO) recanalization techniques and concepts, the success rate of recanalization has been steadily increasing. However, the current data are too limited to draw any reliable conclusions about the efficacy and safety of drug-coated balloons (DCBs) in CTO percutaneous coronary intervention (PCI). Herein, we conducted a meta-analysis to confirm the efficacy of DCB in CTO PCI. METHODS: We systematically searched PubMed, Web of Science and Embase from inception to July 25, 2023. The primary outcome was major advent cardiovascular events (MACE), including cardiac death, nonfatal myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR). The follow-up angiographic endpoints were late lumen enlargement (LLE), reocclusion and restenosis. RESULTS: Five studies with a total of 511 patients were included in the meta-analysis. Across studies, patients were predominantly male (72.9-85.7%) and over fifty years old. The summary estimate rate of MACE was 13.0% (95% CI 10.1%-15.9%, I2 = 0%, p = 0.428). The summary estimate rates of cardiac death and MI were 2.2% (95% CI 0.7%-3.7%, I2 = 0%, p = 0.873) and 1.2% (95% CI -0.2-2.6%, I2 = 13.7%, p = 0.314), respectively. Finally, the pooled incidences of TLR and TVR were 10.1% (95% CI 5.7%-14.5%, I2 = 51.7%, p = 0.082) and 7.1% (95% CI 3.0%-11.2%, I2 = 57.6%, p = 0.070), respectively. Finally, the summary estimate rates of LLE, reocclusion and restenosis were 59.4% (95% CI 53.5-65.3%, I2 = 0%, p = 0.742), 3.3% (95% CI 1.1-5.4%, I2 = 0%, p = 0.865) and 17.5% (95% CI 12.9-22.0%, I2 = 0%, p = 0.623), respectively. CONCLUSION: Accordingly, DCB has the potential to be used as a treatment for CTO in suitable patients.

Comparison of intravascular lithotripsy versus rotational atherectomy for the treatment of severe coronary artery calcification.

BACKGROUND: Calcified lesions are one of the most challenging cases for PCI, where optimal angiographic results and satisfying outcomes are hard to achieve. METHODS: We evaluated the baseline clinical, procedures characteristics and outcomes of patients with severe coronary artery calcification (CAC) who underwent coronary intravascular lithotripsy (IVL) and rotational atherectomy (RA). RESULTS: Respectively 152 and 238 patients who underwent IVL and RA are enrolled from January 2023 to November 2023. Regarding demographic characteristics, the gender proportion, medical history of PCI and smoke history among groups reach statistical significance. Left anterior descending and right coronary artery were the main vessels treated in both groups. The 2.5 and 3.0 mm IVL balloons and 1.5 mm burr were the most commonly used. 99.3% cases were successfully implanted drug-eluting stents after IVL balloon pre-treatment, which was higher than in the group treated with RA. During hospitalization, there were no serious adverse events in the IVL group, but there were two adverse events in the RA group. Procedural complications were higher in the RA group than the IVL group (5.5% vs. 0.7%, P = 0.027). CONCLUSIONS: IVL appears to be safe and effective for the treatment of severe CAC lesions compared to RA.

Deficit Irrigation Effects on Cotton Growth Cycle and Preliminary Optimization of Irrigation Strategies in Arid Environment.

With the changing global climate, drought stress will pose a considerable challenge to the sustainable development of agriculture in arid regions. The objective of this study was to explore the resistance and water demand of cotton plants to water stress during the flowering and boll setting stage. The experimental plot was in Huaxing Farm of Changji city. The plots were irrigated, respectively, at 100% (as the control), 90%, 85% and 80% of the general irrigation amount in the local area. The relationship between the various measured indexes and final yield under different deficit irrigation (DI) treatments was studied. The results showed that deficit irrigation impacted the growth and development processes of cotton during the flowering and boll setting stage. There was a high negative correlation (R2 > 0.95) between the maximum leaf area index and yield. Similarly, there was a high correlation between malondialdehyde content and yield. Meanwhile, 90% of the local cotton irrigation contributed to water saving and even increasing cotton yield. Furthermore, based on the results, the study made an initial optimization to the local irrigation scheme by utilizing the DSSAT model. It was found that changing the irrigation interval to 12 days during the stage could further enhance cotton yield and conserve resources.

The Establishment of a Novel γ-Interferon In Vitro Release Assay for the Differentiation of Mycobacterial Bovis-Infected and BCG-Vaccinated Cattle.

BCG vaccination is increasingly reconsidered in the effective prevention of bovine tuberculosis (bTB). However, the primary challenge in BCG vaccination for cattle is the lack of a technique for differentiating between infected and vaccinated animals (DIVA). This study aimed to establish a novel DIVA diagnostic test based on an interferon-gamma in vitro release assay (IGRA). The plasmid encoding three differential antigens (Rv3872, CFP-10, and ESAT-6) absent in BCG genes but present in virulent M. bovis was previously constructed. Thus, a recombinant protein called RCE (Rv3872, CFP-10, and ESAT-6) was expressed, and an RCE-based DIVA IGRA (RCE-IGRA) was established. The RCE concentration was optimized at 4 µg/mL by evaluating 97 cattle (74 of which were bTB-positive, and 23 were negative) using a commercial IGRA bTB diagnostic kit. Further, 84 cattle were tested in parallel with the RCE-IGRA and commercial PPD-based IGRA (PPD-IGRA), and the results showed a high correlation with a kappa value of 0.83. The study included BCG-vaccinated calves (n = 6), bTB-positive cattle (n = 6), and bTB-negative non-vaccinated calves (n = 6). After 3 months post-vaccination, PPD-IGRA generated positive results in both vaccinated and infected calves. However, RCE-IGRA developed positive results in infected calves but negative results in vaccinated calves. In conclusion, this DIVA method has broad prospects in differentiating BCG vaccination from natural infection to prevent bTB.

Individual- and Herd-Level Milk ELISA Test Status and Incidence for Paratuberculosis in Hubei Province, China.

Mycobacterium avium subsp. paratuberculosis (MAP) is responsible for the persistent infectious illness known as bovine paratuberculosis, which is one of the most easily overlooked diseases in China amid a lack of epidemiological data. In this study, we evaluated the agreement of milk and blood antibody tests for paratuberculosis and showed an overall agreement of 92.0%, with a 95.0% negative coincidence rate and a 78.6% positive coincidence rate. The milk test was then used to examine the prevalence and incidence of dairy cows in Hubei Province, China. We found that, at the individual level, the highest lacto-prevalence reached up to 22.9%; the farm-level prevalence was as high as 92.3% (12/13) and 84.6% (11/13) in January and April 2018, respectively. The total incidence risk of all farms was 6% per three months. We also found that large-scale farms had a significantly lower prevalence and incidence than small-scale farms. Finally, the correlation between paratuberculosis and milk quality was evaluated, and we confirmed that MAP can significantly alter milk quality and raise somatic cell counts in the milk. This study provides valuable information for assessing the prevalence and incidence risk of paratuberculosis in China. It further provides an essential basis for calling for the prevention and control of paratuberculosis in China.

Investigation of the safety and protective efficacy of an attenuated and marker M. bovis-BoHV-1 combined vaccine in bovines.

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.

Longitudinal vibration control of a double-rod system by employing nonlinear energy sinks.

This study aims to potential the potential utilization of nonlinear energy sinks (NESs) for controlling longitudinal vibrations in a double-rod system. The research introduces a longitudinal vibration prediction model for a double-rod system equipped with NESs. The generalized Hamilton principle is employed to derive governing equations of the double-rod system. The longitudinal vibration responses of the double-rod system are numerically solved through the application of Galerkin truncation method. The longitudinal vibration responses of the double-rod system are impacted by NESs, as they yield accurate numerical results. The installation of both NES 1 and NES 2 concurrently is recommended for mitigating the vibration of the double-rod system. Under reasonable single-frequency excitations, modifying the parameters of NESs can significantly alter both the vibration state and magnitudes of vibration in the double-rod system. Furthermore, the synchronous optimization of parameters in NES 1 and NES 2 is crucial for effectively controlling vibrations in the double-rod system. Sensitive parameter areas of NESs provide the possibility of controlling the vibration of the double-rod system by utilizing NESs.

A study of analyzing longitudinal dynamic behavior of a double-rod system with longitudinal nonlinear supports.

In engineering, shafting systems are typically subjected to longitudinal vibration excitations, which may result in unwanted vibration. To study the control of longitudinal vibration in shafting systems, they can be simplified to rod structures. Currently, engineers have attempted to apply the nonlinear principle to design nonlinear supports to control the vibration of flexible structures. However, the flexible structures referenced in the literature are usually composed of a single component, which limits the application of nonlinear supports to more complex structures. To explore the potential application of nonlinear supports in marine engineering, this work introduces a longitudinal vibration prediction model for a double-rod system equipped with longitudinal nonlinear supports. The generalized Hamilton principle is used to derive the governing equations for the double-rod system with longitudinal nonlinear supports. The longitudinal vibration responses of the double-rod system are numerically solved using the Galerkin truncation method. The numerical results confirm that a 1-term truncation number guarantees the stability of the longitudinal vibration prediction model. Under certain conditions, the longitudinal vibration responses are significantly affected by longitudinal nonlinear supports. It is recommended to install longitudinal nonlinear supports on both Rod 1 and Rod 2 simultaneously to suppress vibration in the first two main resonance orders. With reasonable excitations, the vibration state and magnitudes of the double-rod system can be effectively controlled by adjusting the longitudinal nonlinear supports. Complex longitudinal vibration responses are more readily induced by altering the parameters of the longitudinal nonlinear support installed on Rod 1. Choosing appropriate parameters for the nonlinear supports on Rod 1 and Rod 2 positively contributes to the reduction of vibration in the double-rod system.

Land-use change interacts with island biogeography to alter bird community assembly.

Anthropogenic activities have reshaped biodiversity on islands worldwide. However, it remains unclear how island attributes and land-use change interactively shape multiple facets of island biodiversity through community assembly processes. To answer this, we conducted bird surveys in various land-use types (mainly forest and farmland) using transects on 34 oceanic land-bridge islands in the largest archipelago of China. We found that bird species richness increased with island area and decreased with isolation, regardless of the intensity of land-use change. However, forest-dominated habitats exhibited lower richness than farmland-dominated habitats. Island bird assemblages generally comprised species that share more similar traits or evolutionary histories (i.e. functional and/or phylogenetic clustering) than expected if assemblages were randomly assembled. Contrary to our expectations, we observed that bird assemblages in forest-dominated habitats were more clustered on large and close islands, whereas assemblages in farmland-dominated habitats were more clustered on small islands. These contrasting results indicate that land-use change interacts with island biogeography to alter the community assembly of birds on inhabited islands. Our findings emphasize the importance of incorporating human-modified habitats when examining the community assembly of island biota, and further suggest that agricultural landscapes on large islands may play essential roles in protecting countryside island biodiversity.

Diselenide-Containing Polymer Based on New Antitumor Mechanism as Efficient GSH Depletion Agent for Ferroptosis Therapy.

Glutathione (GSH) depletion-induced ferroptosis has emerged as a promising treatment for malignant cancer. It works by inactivating glutathione peroxidase 4 (GPX4) and facilitating lipid peroxidation. However, effectively delivering inducers and depleting intracellular GSH remains challenging due to the short half-lives and high hydrophobicity of small-molecule ferroptosis inducers. These inducers often require additional carriers. Herein, diselenide-containing polymers can consume GSH to induce ferroptosis for pancreatic cancer therapy. The diselenide bonds are controllably built into the backbone of the polycarbonate with a targeting peptide CRGD (Cys-Arg-Gly-Asp), which allows for self-assembly into stable nanoparticles (denoted CRNSe) for self-delivery. Significantly, at a concentration of 12 µg mL-1, CRNSe binds to the active site cysteine of GSH resulting in a thorough depletion of GSH. In contrast, the disulfide-containing analog only causes a slight decrease in GSH level. Moreover, the depletion of GSH inactivates GPX4, ultimately inducing ferroptosis due to the accumulation of lipid peroxide in BxPC-3 cells. Both in vitro and in vivo studies have demonstrated that CRNSe exhibits potent tumor suppressive ability with few side effects on normal tissue. This study validates the anti-tumor mechanism of diselenide-containing polymers in addition to apoptosis and also provides a new strategy for inherently inducing ferroptosis in cancer therapy.

Prevalence, Molecular Characteristics and Virulence Identification of Bovine Parainfluenza Virus Type 3 in China.

Bovine parainfluenza virus type 3 (BPIV-3) is one of the major pathogens of the bovine respiratory disease complex (BRDC). BPIV-3 surveillance in China has been quite limited. In this study, we used PCR to test 302 cattle in China, and found that the positive rate was 4.64% and the herd-level positive rate was 13.16%. Six BPIV-3C strains were isolated and confirmed by electron microscopy, and their titers were determined. Three were sequenced by next-generation sequencing (NGS). Phylogenetic analyses showed that all isolates were most closely related to strain NX49 from Ningxia; the genetic diversity of genotype C strains was lower than strains of genotypes A and B; the HN, P, and N genes were more suitable for genotyping and evolutionary analyses of BPIV-3. Protein variation analyses showed that all isolates had mutations at amino acid sites in the proteins HN, M, F, and L. Genetic recombination analyses provided evidence for homologous recombination of BPIV-3 of bovine origin. The virulence experiment indicated that strain Hubei-03 had the highest pathogenicity and could be used as a vaccine candidate. These findings apply an important basis for the precise control of BPIV-3 in China.

Exosomal hsa_circ_0093884 derived from endothelial progenitor cells promotes therapeutic neovascularization via miR-145/SIRT1 pathway.

Therapeutic neovascularization is a strategy to promote blood vessel growth and improve blood flow, which is critical to tissue repair and regeneration in ischemic diseases. Here, we investigated the role of endothelial progenitor cell - derived exosomes (EPC-Exos) in therapeutic neovascularization and clarified the mechanism of hsa_circ_0093884 in EPC-Exos mediated neovascularization. Injection of EPC-Exos improved mouse ischemic hindlimb perfusion, promoted angiogenesis in Matrigel plugs and mouse skin wound healing. In vitro coculture with EPC-Exos improved HUVEC proliferation, angiogenic and migration ability, while alleviated hypoxia-induced apoptosis. hsa_circ_0093884 was identified from eleven types of circRNA derived from SIRT1 and proved to be enriched in EPC-Exos. Overexpression of hsa_circ_0093884 in EPC-Exos further enhanced the angiogenic capacity, while knockdown of hsa_circ_0093884 abolished the benefits. Mechanistically, EPC-Exos mediated shuttling of hsa_circ_0093884 induced cytoplasmic sponge of miR-145, thereby releasing repression of SIRT1. In vitro co-transfection indicated silence of miR-145 further strengthened the angiogenic effect of hsa_circ_0093884, while overexpression of miR-145 inhibited hsa_circ_0093884 mediated angiogenesis and abolished the beneficial effect of EPC-Exos. Furthermore, in vivo experiments using endothelial specific SIRT1 conditional knockout mice indicated hsa_circ_0093884 overexpressing EPC-Exos failed to promote therapeutic neovascularization in SIRT1cKO mice. Collectively, our results demonstrated that EPC-Exos promoted therapeutic neovascularization through hsa_circ_0093884/miR-145/SIRT1 axis.

-COOH & -OH Condensation Reaction Utilization for Biomass FDCA-based Polyesters.

A green and sustainable -COOH & -OH condensation solution polymerization method was hereby reported for FDCA-based polyesters to avoid discoloration and toxic solvents. First, taking poly(ethylene 2,5-furandicarboxylate) (PEF) as the representative of FDCA-based polyester, enabling good white appearance PEF with Mn=6.51×103 g mol-1 from FDCA and ethylene glycol in green solvent γ-valerolactone (GVL), catalyzed by 4-dimethylaminopyridine (DMAP) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC). Additionally, the molecular weight of PEF was rapidly improved (Mn >2.5×104 g mol-1) via remelting polycondensation within minutes, with the dispersity still kept relatively low dispersity (D<1.40). Importantly, the -COOH & -OH condensation solution polymerization method was successfully applied for the synthesis of various FDCA-based polyesters, including diols with varying carbon chain lengths (3 to 11 carbons) and cycloalkyl diols, especially the applicability of this method to diols containing C=C double bonds, which was found to exhibit low heat resistance. Lastly, assisting with 13C labeled 1,4-succinic acid and in-situ 13C-NMR, an in-depth study of the possible catalytic mechanism was proposed, by which, EDC activated FDCA, and then DMAP catalyzed it with diol to yield macromolecular chain of polyester. Overall, the results provided a green and sustainable strategy for the synthesis of FDCA-based polyesters.

Isolation and Characterization of Paenibacillus polymyxa B7 and Inhibition of Aspergillus tubingensis A1 by Its Antifungal Substances.

Screening of Bacillus with antagonistic effects on paddy mold pathogens to provide strain resources for biological control of mold in Oryza sativa L. screening of Bacillus isolates antagonistic towards Aspergillus tubingensis from rhizosphere soil of healthy paddy; classification and identification of antagonistic strains by biological characteristics and 16S rDNA sequence analysis; transcriptome sequencing after RNA extraction from Bacillus-treated Aspergillus tubingensis; and extraction of inhibitory crude proteins of Bacillus by ammonium sulfate precipitation; inhibitory crude protein and Bacillus spp. were treated separately for A. tubingensis and observed by scanning electron microscopy (SEM). An antagonistic strain of Bacillus, named B7, was identified as Paenibacillus polymyxa by 16S rDNA identification and phylogenetic evolutionary tree comparison analysis. Analysis of the transcriptome results showed that genes related to secondary metabolite biosynthesis such as antifungal protein were significantly downregulated. SEM results showed that the mycelium of A. tubingensis underwent severe rupture after treatment with P. polymyxa and antifungal proteins, respectively. In addition, the sporocarp changed less after treatment with P. polymyxa, and the sporangium stalks had obvious folds. P. polymyxa B7 has a good antagonistic effect against A. tubingensis and has potential for biocontrol applications of paddy mold pathogens.

Identification of Reduced mTOR T1262 Phosphorylation as a Novel Mechanism and Therapeutic Target of Apoptosis in Senescent Cardiomyocytes: Aging and Cardiomyocyte Apoptosis.

The mechanisms through which aging increases heart injury remain partially understood. Protein phosphorylation plays a critical regulatory role in cell survival and death. Using an unbiased phosphoproteomics approach, we aimed to identify the proteins whose phosphorylation could be causatively related to aging-related cardiomyocyte apoptosis and elucidate the underlying mechanisms. Comparative phosphoproteomics was conducted on cardiac tissues obtained from young (8 weeks) and aged (24 months) mice. Our findings revealed that the Mammalian Target of Rapamycin phosphorylation at T1262 (mTORT1262) was reduced in the aging heart. Immunohistochemical and Western blot analyses confirmed these findings in aging myocardia and D-galactose-induced senescent AC16 cardiomyocytes. In hypoxia/reoxygenation cardiomyocytes, mTORT1262 phosphorylation deficiency (mTORT1262A, lentivirus-mediated transfection) inhibited AKT1, suppressed NF-κB, activated FOXO1/3a signaling, and ultimately exacerbated apoptosis. Conversely, mTORT1262 pseudophosphorylation (mTORT1262E) exhibited opposite effects. Through bioinformatics and CO-IP, purinergic receptor P2X4 (P2X4R) was found to be the possible receptor responsible for mTORT1262 phosphorylation. Knockdown of P2X4R increased apoptosis, whereas its overexpression decreased it. In senescent cardiomyocytes, P2X4R expression and mTORT1262 and AKT1S473 phosphorylation were reduced, NF-κB signaling was suppressed, and FOXO1/3a signaling was activated. We demonstrated that P2X4R downregulation and the subsequent reduction of mTORT1262 phosphorylation is a novel mechanism contributing to cardiomyocyte apoptosis in aging hearts. The P2X4R-mTOR-AKT1 signaling pathway represents a potential therapeutic target against accelerated cardiac injury in aging.

Advances in immunotherapy for biliary tract cancers.

ABSTRACT: Biliary tract cancers (BTC), a heterogeneous disease with poor prognosis, including gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC). Although surgery is currently the primary regimen to treat BTC, most BTC patients are diagnosed at an advanced stage and miss the opportunity of surgical eradication. As a result, non-surgical therapy serves as the main intervention for advanced BTC. In recent years, immunotherapy has emerged as one of the most promising therapies in a number of solid cancers, and it includes immune checkpoint inhibitors (ICIs) monotherapy or combined therapy, tumor vaccines, oncolytic virus immunotherapy, adoptive cell therapy (ACT), and cytokine therapy. However, these therapies have been practiced in limited clinical settings in patients with BTC. In this review, we focus on the discussion of latest advances of immunotherapy in BTC and update the progress of multiple current clinical trials with different immunotherapies.

Uncovering widespread Anthropocene dietary shifts in Chinese large mammalian herbivores.

The Anthropocene's human-dominated habitat expansion endangers global biodiversity. However, large mammalian herbivores experienced few extinctions during the 20th century, hinting at potentially overlooked ecological responses of a group sensitive to global change. Using dental microwear as a proxy, we studied large herbivore dietary niches over a century across mainland China before (1880s-1910s) and after (1970s-1990s) the human population explosion. We uncovered widespread and significant shifts (interspecific microwear differences increased and intraspecific microwear dispersion expanded) within dietary niches linked to geographical areas with rapid industrialization and population growth in eastern China. By contrast, in western China, where human population growth was slower, we found no indications of shifts in herbivore dietary niches. Further regression analysis links the intensity of microwear changes to human land-use expansion. These analyses highlight dietary adjustments of large herbivores as a likely key factor in their adaptation across a century of large-scale human-driven changes.