Age-Related Variations in the Population of Active Secondary Hair Follicles, Oxidative Stress and Antioxidant Parameters in Cashmere Goats.

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (p < 0.05). Cashmere production was higher in goats aged 2-4 years compared to those aged 5-7 years (p < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2-4 years) having a higher population than those aged 5-7 years (p < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (p < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (p < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (p < 0.05). Interestingly, the skin's antioxidant capacity and oxidative damage exhibited significant positive and negative correlations with the population of active secondary hair follicles (p < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

Cu Promoted the Dynamic Evolution of Ni-Based Catalysts for Polyethylene Terephthalate Plastic Upcycling.

Upcycling plastic wastes into value-added chemicals is a promising approach to put end-of-life plastic wastes back into their ecocycle. As one of the polyesters that is used daily, polyethylene terephthalate (PET) plastic waste is employed here as the model substrate. Herein, a nickel (Ni)-based catalyst was prepared via electrochemically depositing copper (Cu) species on Ni foam (NiCu/NF). The NiCu/NF formed Cu/CuO and Ni/NiO/Ni(OH)2 core-shell structures before electrolysis and reconstructed into NiOOH and CuOOH/Cu(OH)2 active species during the ethylene glycol (EG) oxidation. After oxidation, the Cu and Ni species evolved into more reduced species. An indirect mechanism was identified as the main EG oxidation (EGOR) mechanism. In EGOR, NiCu60s/NF catalyst exhibited an optimal Faradaic efficiency (FE, 95.8%) and yield rate (0.70 mmol cm-2 h-1) for formate production. Also, over 80% FE of formate was achieved when a commercial PET plastic powder hydrolysate was applied. Furthermore, commercial PET plastic water bottle waste was employed as a substrate for electrocatalytic upcycling, and pure terephthalic acid (TPA) was recovered only after 1 h electrolysis. Lastly, density functional theory (DFT) calculation revealed that the key role of Cu was significantly reducing the Gibbs free-energy barrier (ΔG) of EGOR's rate-determining step (RDS), promoting catalysts' dynamic evolution, and facilitating the C-C bond cleavage.

Sex-specific scaling of leaf phosphorus vs. nitrogen under unequal reproductive requirements in Eurya japonica, a dioecious plant.

PREMISE: Previous work searching for sexual dimorphism has largely relied on the comparison of trait mean vectors between sexes in dioecious plants. Whether trait scaling (i.e., the ratio of proportional changes in covarying traits) differs between sexes, along with its functional significance, remains unclear. METHODS: We measured 10 vegetative traits pertaining to carbon, water, and nutrient economics across 337 individuals (157 males and 180 females) of the diocious species Eurya japonica during the fruiting season in eastern China. Piecewise structural equation modeling was employed to reveal the scaling relationships of multiple interacting traits, and multivariate analysis of (co)variance was conducted to test for intersexual differences. RESULTS: There was no sexual dimorphism in terms of trait mean vectors across the 10 vegetative traits in E. japonica. Moreover, most relationships for covarying trait pairs (17 out of 19) exhibited common scaling slopes between sexes. However, the scaling slopes for leaf phosphorus (P) vs. nitrogen (N) differed between sexes, with 5.6- and 3.0-fold increases of P coinciding with a 10-fold increase of N in male and female plants, respectively. CONCLUSIONS: The lower ratio of proportional changes in P vs. N for females likely reflects stronger P limitation for their vegetative growth, as they require greater P investments in fruiting. Therefore, P vs. N scaling can be a key avenue allowing for sex-specific strategic optimization under unequal reproductive requirements. This study uncovers a hidden aspect of secondary sex character in dioecious plants, and highlights the use of trait scaling to understand sex-defined economic strategies.

Sub-Nanometer Mono-Layered Metal-Organic Frameworks Nanosheets for Simulated Flue Gas Photoreduction.

The dilemma between the thickness and accessible active site triggers the design of porous crystalline materials with mono-layered structure for advanced photo-catalysis applications. Here, a kind of sub-nanometer mono-layered nanosheets (Co-MOF MNSs) through the exfoliation of specifically designed Co3 cluster-based metal-organic frameworks (MOFs) is reported. The sub-nanometer thickness and inherent light-sensitivity endow Co-MOF MNSs with fully exposed Janus Co3 sites that can selectively photo-reduce CO2 into formic acid under simulated flue gas. Notably, the production efficiency of formic acid by Co-MOF MNSs (0.85 mmol g-1 h-1) is ≈13 times higher than that of the bulk counterpart (0.065 mmol g-1 h-1) under a simulated flue gas atmosphere, which is the highest in reported works up to date. Theoretical calculations prove that the exposed Janus Co3 sites with simultaneously available sites possess higher activity when compared with single Co site, validating the importance of mono-layered nanosheet morphology. These results may facilitate the development of functional nanosheet materials for CO2 photo-reduction in potential flue gas treatment.

CircRNA CDR1as affects functional repair after spinal cord injury and regulates fibrosis through the SMAD pathway.

Spinal cord injury (SCI) is a complex problem in modern medicine. Fibroblast activation and fibroscarring after SCI impede nerve recovery. Non-coding RNA plays an important role in the progression of many diseases, but the study of its role in the progression of spinal fibrosis is still emerging. Here, we investigated the function of circular RNAs, specifically antisense to the cerebellar degeneration-related protein 1 (CDR1as), in spinal fibrosis and characterized its molecular mechanism and pathophysiology. The presence of CDR1as in the spinal cord was verified by sequencing and RNA expression assays. The effects of inhibition of CDR1as on scar formation, inflammation and nerve regeneration after spinal cord injury were investigated in vivo and in vitro. Further, gene expression of miR-7a-5p and protein expression of transforming Growth Factor Beta Receptor II (TGF-ßR2) were measured to evaluate their predicted interactions with CDR1as. The regulatory effects and activation pathways were subsequently verified by miR-7a-5p inhibitor and siCDR1as. These results indicate that CDR1as/miR-7a-5p/TGF-ßR2 interactions may exert scars and nerves functions and suggest potential therapeutic targets for treating spinal fibrotic diseases.

[Morphological study of sexual reproductive disorders in Ligusticum chuanxiong].

Chuanxiong Rhizoma is a well-known Sichuan-specific herbal medicine. Its original plant, Ligusticum chuanxiong, has been cultivated asexually for a long time. L. chuanxiong has sexual reproductive disorders, which restricts its germplasm innovation. However, there is little research on the reproductive system of L. chuanxiong. This study is based on a comparative anatomical research approach, using morphological dissection, paraffin sectioning, staining and compression, and combined with scanning electron microscopy technology, to observe and compare the flowers, fruits, and seeds at various stages of reproductive growth of L. chuanxiong and its wild relative L. sinense. The results showed that the meiosis of pollen mother cells is abnormal in L. chuanxiong anthers, and the size and number of microspores are uneven and inconsistent in the tetrad stage. tapetum cells are not completely degenerated during anther development. During the pollen ripening stage, there are fine cracks in the anther wall, while most anthers could not release pollen normally. The surface of mature pollen grains is concave and partially deformed, and the pollens are all inactive and cannot germinate in vitro. The starch, polysaccharides, and lipids in the pollen were insufficient. The filaments of L. chuanxiong are short at the flowering stage and recurved downward. Double-hanging fruits were observed in the fruiting stage, being wrinkled; with shriveled seeds. Compared with L. sinense at the same stage, the anthers of L. sinense developed normally, and the pollen grains are vigorous and can germinate in vitro. The double-hanging fruits of L. sinense are full and normal; at the flowering period, the filaments are long and erect, significantly higher than the stigma. Mature blastocysts are visible in the ovary of both L. chuanxiong and L. sinense, and there is no significant difference in stigmas. The conclusion is that during the development of L. chuanxiong stamens, the meiosis of pollen mother cells is abnormal, and tetrad, tapetum, filament and other pollen structures develop abnormally. L. chuanxiong has the characteristic of male infertility, which is an important reason for its sexual reproductive disorders.

Tuning Surface Potential Polarization to Enhance N2 Affinity for Ammonia Electrosynthesis.

Electrocatalytic N2 reduction reaction (NRR) to synthesize ammonia is a sustainable reaction that is expected to replace Haber Bosch process. Laminated Bi2 WO6 has great potential as an NRR electrocatalyst, however, the effective activity requires that the inert substrate is fully activated. Here, for the first time, success is achieved in activating the Bi2 WO6 basal planes with NRR activity through Ti doping. The introduction of Ti successfully tunes the surface potential distribution and enhances the N2 adsorption. The subsequently strong hybrid coupling of d(Ti)-p(N) orbitals fills the electronic state of N2 antibonding molecular orbital, which greatly weakens the bonding strength of N≡N bonds. Further, in situ synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectrum and theoretical calculations show that surface potential polarization enhances the adsorption of HNN* by Bi-Ti dual-metal sites, which is beneficial for the subsequent activation hydrogenation process. The Ti-Bi2 WO6 nanosheets achieve 11.44% Faradaic efficiency (-0.2 V vs. RHE), a NH3 yield rate of 23.14 µg mg-1  h-1 (15 N calibration), and satisfactory stability in 0.1 M HCl environment. The mutual assistance of theory and experiment can help understand and develop of excellent two-dimensional (2D) materials for the NRR.

Trans-cinnamaldehyde fumigation inhibits Escherichia coli by affecting the mechanism of intracellular biological macromolecules.

This study aimed to determine the antibacterial mechanism of cinnamaldehyde fumigation in Escherichia coli (E. coli). Through vapour fumigation, cinnamaldehyde was confirmed to exhibit effective antibacterial activity against E. coli. The minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) were 0.25 µL/mL and 0.5 µL/mL, respectively. Based on transmission electron microscopy, the wrinkled bacterial cells observed after fumigation could be related to the leakage of intracellular substances. Laser tweezers Raman spectroscopy revealed changes in the main chain of proteins, the hydrogen bond system and spatial structure, and single- and double-stranded DNA breaks. In addition, breakage of the fatty acyl chain backbone was found to affect the vertical order degree of the lipid bilayer and cell membrane fluidity, thereby inhibiting the growth of E. coli. Overall, our findings indicate that cinnamaldehyde fumigation inhibits E. coli growth by inducing changes in intracellular biological macromolecules.

A novel electrode for simultaneous detection of multiple heavy metal ions without pre-enrichment in food samples.

Integrating a pre-enrichment step into electrochemical detection methodologies has traditionally been employed to enhance the performance of heavy metal detection. However, this augmentation also introduces a degree of intricacy into the sensing process and increases energy consumption. In this work, Mo-doped WO3 is grown in situ on carbon cloth by one-step electrodeposition. The electrode detect multiple heavy metal ions simultaneously in the range of 0.1-100.0 µM with LODs ranging from 11.2 to 17.1 nM. The electrode successfully detected heavy metal ions in diverse food samples. This pioneering detection strategy realized the direct and simultaneous detection of multiple heavy metal ions by utilizing the valence property of WO3 and oxygen vacancies generated by molybdenum doping. The Mo-WO3/CC pre-enrichment-free detection electrode boasts straightforward preparation, a streamlined detection procedure, swift response kinetics, and superior performance relative to previously reported electrodes, which makes it possible to develop a portable heavy metal ion detection device.

Potential Anti-Gouty Arthritis of Citronella Essential Oil and Nutmeg Essential Oil through Reducing Oxidative Stress and Inhibiting PI3K/Akt/mTOR Activation-Induced NLRP3 Activity.

Citronella and Nutmeg are two common spices used for seasoning and medicinal purposes, both of which have significant economic value. This study aimed to investigate whether Citronella essential oil and Nutmeg essential oil (NEO) can ameliorate monosodium urate (MSU)-induced gouty arthritis in rats and the potential mechanisms. The results showed that CEO and NEO reduced swelling and redness at joint sites, inhibited neutrophil infiltration, and limited proinflammatory mediator secretion in mice with MSU-induced gouty arthritis. Based on the results of network pharmacology, molecular docking, and western blotting, CEO and NEO may exert anti-gouty arthritis effects by reducing the expression of reactive oxygen species and oxidative stress and downregulating the phosphorylation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting the production of the NLRP3 inflammasome and inhibiting the production of inflammatory cytokines. Therefore, these two essential oils show potential for use as adjuvant treatments for gouty arthritis in specific aromatherapy products or food seasonings.

Sensitive Electrochemical Detection of Ammonia Nitrogen via a Platinum-Zinc Alloy Nanoflower-Modified Carbon Cloth Electrode.

As a common water pollutant, ammonia nitrogen poses a serious risk to human health and the ecological environment. Therefore, it is important to develop a simple and efficient sensing scheme to achieve accurate detection of ammonia nitrogen. Here, we report a simple fabrication electrode for the electrochemical synthesis of platinum-zinc alloy nanoflowers (PtZn NFs) on the surface of carbon cloth. The obtained PtZn NFs/CC electrode was applied to the electrochemical detection of ammonia nitrogen by differential pulse voltammetry (DPV). The enhanced electrocatalytic activity of PtZn NFs and the larger electrochemical active area of the self-supported PtZn NFs/CC electrode are conducive to improving the ammonia nitrogen detection performance of the sensitive electrode. Under optimized conditions, the PtZn NFs/CC electrode exhibits excellent electrochemical performance with a wide linear range from 1 to 1000 µM, a sensitivity of 21.5 µA µM-1 (from 1 µM to 100 µM) and a lower detection limit of 27.81 nM, respectively. PtZn NFs/CC electrodes show excellent stability and anti-interference. In addition, the fabricated electrochemical sensor can be used to detect ammonia nitrogen in tap water and lake water samples.

Disastrous cerebral and ocular vascular complications after cosmetic facial filler injections: a retrospective case series study.

Soft tissue filler injections are among the most popular facial rejuvenation methods. Cerebral infarction and ophthalmic artery occlusion are rare and catastrophic complications, especially when facial cosmetic fillers are injected by inexperienced doctors. Radiologists and plastic surgeons need to increase their awareness of the complications associated with fillers, which allows early diagnosis and intervention to improve patient prognosis. Regarding the mechanism by which vascular occlusion occurs after facial filler injections, a retrograde embolic mechanism is currently the predominant theory. Numerous case reports have been presented regarding complications associated with injections of facial aesthetics. However, the small sample sizes of these studies did not allow for an adequate assessment of the clinical and imaging manifestations based on the location of the occlusion and the type of filler, and detailed elaboration of multiple cerebral infarctions is also lacking. Therefore, this study aimed to investigate the clinical and radiological features of severe cerebral and ocular complications caused by cosmetic facial filler injections. In addition, we discuss the pathogenesis, treatment, and prognosis of these patients. The clinical, computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) findings were described and analysed. Radiological examinations are crucial for demonstrating severe complications, and brain MRI is especially strongly suggested for patients with cosmetic filler-induced vision loss to identify asymptomatic cerebral infarctions. Extreme caution and care should be taken during facial injections by plastic surgeons.

Three new species of Agaricus from Baiyun Mountain, Guangzhou, China.

Agaricus is a species-rich genus with more than 600 species around the world. In this work, three new species, Agaricus cacainus, A. baiyunensis, and A. praeclarefibrillosus are described from the specimens collected at Baiyun Mountain, Guangzhou, China, a subtropical area with a monsoon maritime climate, based on phylogenetic analyses and morphological examinations of internal transcribed spacer (ITS1-5.8S-ITS2 = ITS), D1/D2 domains of the large subunit of ribosomal DNA (28S), and a part of translation elongation factor 1-alpha (TEF1). Agaricus cacainus in A. sect. Amoeni is characterized by a parabolic to applanate, slightly depressed pileus covered with chocolate brown, appressed, triangular squamules against white background, a white, furfuraceous stipe, an unchanging context when cut, a fragile and evanescent annulus, usually 4- or 2-spored basidia, and mostly pyriform cheilocystidia. Agaricus baiyunensis in A. sect. Minores has a pileus with a slightly truncate top covered with light brown, downy-wooly fibrillose scales and a light yellowish stipe with membranous annulus. Agaricus praeclarefibrillosus in A. sect. Brunneopicti is characterized by a pileus surface with brownish, triangular, recurved scales and longitudinally splitting lines toward margin, a cottony stipe with white, tiny, recurved fibrils, a single annulus, and variously shaped cheilocystidia, with sparsely ornamented basidiospores. The detailed comparison of their morphological characteristics with closely related species is provided.

Single-Component Photochemical Afterglow Near-Infrared Luminescent Nano-Photosensitizers: Bioimaging and Photodynamic Therapy.

Long afterglow luminescence-guided photodynamic therapy (PDT) performs advantages of noninvasiveness, spatiotemporal controllability, and higher signal to noise ratio. Photochemical afterglow (PCA) system emitting afterglow in an aqueous environment is highly suitable for biomedical applications, but still faces the challenges of poor tissue penetration depth and responsive sensitivity. In this work, two novel compounds, Iso-TPA and ABEI-TPA, are designed and synthesized to integrate the PCA system as a single component by coupling near-infrared (NIR) photosensitizers with singlet oxygen cache units, respectively. Both compounds emit NIR afterglow based on photochemical reaction. ABEI-TPA exhibits higher photoluminescence quantum efficiency with nonconjugated linkage, while Iso-TPA with conjugated linkage possesses better reactive oxygen species generation efficiency to achieve stronger PCA and effective PDT, which is ascribed to stronger intramolecular charge transfer effect of Iso-TPA. Iso-TPA nanoparticles can achieve effective long-lasting NIR afterglow in vivo bioimaging up to 120 s with higher imaging resolution and outstanding PDT efficacy of tumor, exhibiting promising potential on bioimaging and therapy.

Enhanced Sensitivity of Electrochemical Sensors for Ammonia-Nitrogen via In-Situ Synthesis PtNi Nanoleaves on Carbon Cloth.

Pt-based electrochemical ammonia-nitrogen sensors played a significance role in real-time monitoring the ammonia-nitrogen concentration. The alloying of Pt and transition metals was one of the effective ways to increase the detectability of the sensitive electrode. In this paper, a self-supported electrochemical electrode for the detection of ammonia nitrogen was obtained by the electrodeposition of PtNi alloy nanoleaves on a carbon cloth (PtNi-CC). Experimental results showed that the PtNi-CC electrode exhibited enhanced detection performance with a wide linear range from 0.5 to 500 µM, high sensitivity (7.83 µA µM-1 cm-2 from 0.5 to 150 µM and 0.945 µA µM-1 cm-2 from 150 to 500 µM) and lower detection limit (24 nM). The synergistic effect between Pt and Ni and the smaller lattice spacing of the PtNi alloy were the main reasons for the excellent performance of the electrode. This work showed the great potential of Pt-based alloy electrodes for the detection of ammonia-nitrogen.

Constructing a personalized prognostic risk model for colorectal cancer using machine learning and multi-omics approach based on epithelial-mesenchymal transition-related genes.

The progression and the metastatic potential of colorectal cancer (CRC) are intricately linked to the epithelial-mesenchymal transition (EMT) process. The present study harnesses the power of machine learning combined with multi-omics data to develop a risk stratification model anchored on EMT-associated genes. The aim is to facilitate personalized prognostic assessments in CRC. We utilized publicly accessible gene expression datasets to pinpoint EMT-associated genes, employing a CoxBoost algorithm to sift through these genes for prognostic significance. The resultant model, predicated on gene expression levels, underwent rigorous independent validation across various datasets. Our model demonstrated a robust capacity to segregate CRC patients into distinct high- and low-risk categories, each correlating with markedly different survival probabilities. Notably, the risk score emerged as an independent prognostic indicator for CRC. High-risk patients were characterized by an immunosuppressive tumor milieu and a heightened responsiveness to certain chemotherapeutic agents, underlining the model's potential in steering tailored oncological therapies. Moreover, our research unearthed a putative repressive interaction between the long non-coding RNA PVT1 and the EMT-associated genes TIMP1 and MMP1, offering new insights into the molecular intricacies of CRC. In essence, our research introduces a sophisticated risk model, leveraging machine learning and multi-omics insights, which accurately prognosticates outcomes for CRC patients, paving the way for more individualized and effective oncological treatment paradigms.

Coarse particles compensate for missing daytime sources of nitrous acid and enhance atmospheric oxidation capacity in a coastal atmosphere.

Large missing sources of daytime atmospheric nitrous acid (HONO), a vital source of hydroxyl radicals (OH) through its photolysis, frequently exist in global coastal regions. In this study, ambient HONO and relevant species were measured at a coastal site in the Pearl River Delta (PRD), China, during October 2019. Relatively high concentrations (0.32 ± 0.19 ppbv) and daytime peaks at approximately 13:00 of HONO were observed, and HONO photolysis was found to be the dominant (55.5 %) source of the primary OH production. A budget analysis of HONO based on traditional sources suggested large unknown sources during the daytime (66.4 %), which had a significant correlation with the mass of coarse particles (PM2.5-10) and photolysis frequency (J(NO2)). When incorporating photolysis of the abundant nitrate measured in coarse particles with a reasonable enhancement factor relative to fine particles due to favorable aerosol conditions, the missing daytime sources of HONO could be fully compensated by coarse particles serving as the largest source at this coastal site. Our study revealed great potential of coarse particles as a strong daytime HONO source, which has been ignored before but can efficiently promote NOx recycling and thus significantly enhance atmospheric oxidation capacity.

Validation and update of a clinical score model to predict technical difficulty of colorectal endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND AND AIMS: The Zhongshan colorectal endoscopic submucosal dissection (CR-ESD) score model was proposed to grade the technical difficulty of CR-ESD. The objective of this study was to prospectively validate and update the score model. METHODS: A multicenter prospective cohort analysis of CR-ESD was conducted. Individual data on patients, lesions, and outcomes of CR-ESD were used to validate the original model and further refine the difficulty of the prediction model. Data were randomly divided into discovery and internal validation cohorts. A multivariate Cox regression analysis was conducted on the discovery cohort to develop an updated risk-scoring system, which was then validated. RESULTS: Five hundred forty-eight patients with 565 colorectal lesions treated by ESD from 4 hospitals were included. In the prospective validation cohort, the area under the receiver-operating characteristic (ROC) curve for the original model was .707. Six risk factors were identified and assigned point values: tumor size (2 points for 30-50 mm, 3 points for ≥50 mm), at least two-thirds circumference of the lesion (3 points), tumor location in the cecum (2 points) or flexure (2 points), laterally spreading tumor-nongranular lesions (1 point), preceding biopsy sampling (1 point), and NBI International Colorectal Endoscopic type 3 (3 points). The updated model had an area under the ROC curve of .738 in the discovery cohort and of .782 in the validation cohort. Cases were categorized into easy (score = 0-1), intermediate (score = 2-3), difficult (score = 4-6), and very difficult (score ≥7) groups. Satisfactory discrimination and calibration were observed. CONCLUSIONS: The original model achieved an acceptable level of prediction in the prospective cohort. The updated model exhibited superior performance and can be used in place of the previous version. (Clinical trial registration number: ChiCTR2100047087.).

Hypoxia is correlated with the tumor immune microenvironment: Potential application of immunotherapy in bladder cancer.

OBJECTIVE: Hypoxia, which can considerably affect the tumor microenvironment, hinders the use of immunotherapy in bladder cancer (BLCA). Therefore, we aimed to identify reliable hypoxia-related biomarkers to guide clinical immunotherapy in BLCA. METHODS: Using data downloaded from TCGA-BLCA cohort, we determined BLCA subtypes which divide 408 samples into different subtypes. Tumor immune infiltration levels of two clusters were quantified using ssGSEA, MCPcounter, EPIC, ESTIMATE, and TIMER algorithms. Next, we constructed a hypoxia score based on the expression of hypoxia-related genes. The IMvigor210 cohort and SubMap analysis were used to predict immunotherapeutic responses in patients with different hypoxia scores. Hub genes were screened using cytoscape, immunohistochemistry (IHC), and multispectral immunofluorescence were used to detect the spatial distribution of immune markers. RESULTS: Patients with BLCA were categorized into cluster1 (n = 227) and Cluster2 (n = 181). Immune infiltration and expression of immune markers were higher in Cluster1. Immune infiltration was also more obvious in the high-hypoxia score group which related to a better predicted response to immunotherapy. IHC, and multispectral immunofluorescence confirmed the importance of TLR8 in immune infiltration and immune phenotype. CONCLUSIONS: BLCA subtype can evaluate the infiltration of immune cells in the tumor microenvironment of different patients. Hypoxia score in this study could effectively predict immunotherapeutic responses in patients with BLCA. TLR8 may be a potential target for clinical immunotherapy.

Bioconjugation and Reaction-Induced Tumor Therapy via Alkynamide-Based Thiol-Yne Click Reaction.

Ferroptosis is associated with the occurrence and development of many diseases, which is the result of an imbalance in cellular metabolism and oxidation-reduction balance. Therefore, it is an effective therapeutic strategy that simultaneously regulating the intracellular oxidation-reduction system. Herein, a click reaction of alkynylamide with thiol groups in the presence of amine or in PBS (pH = 7.4) is developed, which can react efficiently with thiol substances, such as cysteine (Cys), glutathione (GSH), and bovine serum albumin (BSA). Notably, MBTB-PA, an aggregation-induced emission (AIE) photosensitizer with an alkynylamide unit, is synthesized and its intracellular behavior is visualized in situ by fluorescence imaging, demonstrating its excellent ability to target the endoplasmic reticulum. Furthermore, MBTB-PA reacted with proteins in tumor cells, consumed reducing substances, and triggered intracellular oxidative stress, resulting in cell death. Based on this reaction therapy strategy, click reaction is combined with photodynamic therapy to achieve effective killing of tumor cells by simultaneously raising the intracellular oxidative state and reducing the reductive state. This work not only develops an application of click reaction of alkynamide with thiol in bioconjugation and anti-tumor therapy, but also provides feasible ideas for organic reactions in the exploration of organisms.