Association between primary biliary cholangitis with diabetes and cardiovascular diseases: a bidirectional multivariable Mendelian randomization study.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is an autoimmune disease often accompanied by multisystem damage. This study aimed to explore the causal association between genetically predicted PBC and diabetes, as well as multiple cardiovascular diseases (CVDs). METHODS: Genome-wide association studies (GWAS) summary data of PBC in 24,510 individuals of European ancestry from the European Association for the Study of the Liver was used to identify genetically predicted PBC. We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to estimate the impacts of PBC on diabetes (N = 17,685 to 318,014) and 20 CVDs from the genetic consortium (N = 171,875 to 1,030,836). RESULTS: SVMR provided evidence that genetically predicted PBC is associated with an increased risk of type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), heart failure (HF), hypertension, atrial fibrillation (AF), stroke, ischemic stroke, and small-vessel ischemic stroke. Additionally, there was no evidence of a causal association between PBC and coronary atherosclerosis. In the MVMR analysis, PBC maintained independent effects on T1D, HF, MI, and small-vessel ischemic stroke in most models. CONCLUSION: Our findings revealed the causal effects of PBC on diabetes and 7 CVDs, and no causal relationship was detected between PBC and coronary atherosclerosis.

Targeted Stimulation of Micropores by CS2 Extraction on Molecular of Coal.

The targeted stimulation of micropores based on the transformation of coal's molecular structure is proposed due to the chemical properties and difficult-to-transform properties of micropores. Carbon disulfide (CS2) extraction is used as a targeted stimulation to reveal the internal evolution mechanism of micropore transformation. The variations of microcrystalline structures and micropores of bituminous coal and anthracite extracted by CS2 were analyzed with X-ray diffraction (XRD), low-temperature carbon dioxide (CO2) adsorption, and molecular simulation. The results show that CS2 extraction, with the broken chain effect, swelling effect, and aromatic ring rearrangement effect, can promote micropore generation of bituminous coal by transforming the microcrystalline structure. Furthermore, CS2 extraction on bituminous coal can decrease the average micropore size and increase the micropore volume and area. The aromatic layer fragmentation effect of CS2 extraction on anthracite, compared to the micropore generation effect of the broken chain effect and swelling effect, can enlarge micropores more remarkably, as it induces an enhancement in the average micropore size and a decline in the micropore volume and area. The research is expected to provide a theoretical basis for establishing reservoir stimulation technology based on CS2 extraction.

Development of an FAP-Targeted PET Probe Based on a Novel Quinolinium Molecular Scaffold.

Fibroblast activation protein (FAP) has recently gained significant attention as a promising tumor biomarker for both diagnosis and therapeutic applications. A series of radiopharmaceuticals based on fibroblast activation protein inhibitors (FAPIs) have been developed and translated into the clinic. Though some of them such as radiolabeled FAPI-04 probes have achieved favorable in vivo imaging performance, further improvement is still highly desired for obtaining radiopharmaceuticals with a high theranostics potential. In this study, we innovatively designed an FAPI ligand SMIC-3002 by changing the core quinoline motif of FAPI-04 to the quinolinium scaffold. The engineered molecule was further radiolabeled with 68Ga to generate a positron emission tomography (PET) probe, [68Ga]Ga-SMIC-3002, which was then evaluated in vitro and in vivo. [68Ga]Ga-SMIC-3002 demonstrated high in vitro stability, nanomolar affinity for FAP (8 nM for protein, 23 nM for U87MG cells), and specific uptake in FAP-expressing tumors, with a tumor/muscle ratio of 19.1 and a tumor uptake of 1.48 ± 0.03 ID/g% at 0.5 h in U87MG tumor-bearing mice. In summary, the quinolinium scaffold can be successfully used for the development of the FAP-targeted tracer. [68Ga]Ga-SMIC-3002 not only shows high potential for clinical translation but also offers insights into designing a new generation of FAPI tracers.

Spontaneous Transition between Multiple Conductance States and Rectifying Behaviors in an Artificial Single-Molecule Funnel.

It has long been an aspirational goal to create artificial channel structures that replicate the feat achieved by ion channel proteins. Biological ion channels occasionally demonstrate multiple conductance states (known as subconductance), remaining a challenging property to achieve in artificial channel molecules. We report a funnel-shaped single-molecule channel constructed by an electron-deficient macrocycle and two electron-deficient aromatic imide arms. Planar lipid bilayer measurements reveal distinct current recordings, including a closed state, two conducting states, and spontaneous transitions between the three states, resembling the events seen in biological ion channels. The transitions result from conformational changes induced by chloride transport in the channel molecule. Both opening states show a non-linear and rectifying I-V relationship, indicating voltage-dependent transport due to the asymmetrical channel structure. This work could enhance our understanding of ion permeation and channel opening mechanism.

Development and validation of a neoadjuvant chemotherapy pathological complete remission model based on Reg IV expression in breast cancer tissues: a clinical retrospective study.

OBJECTIVE: To develop and authenticate a neoadjuvant chemotherapy (NACT) pathological complete remission (pCR) model based on the expression of Reg IV within breast cancer tissues with the objective to provide clinical guidance for precise interventions. METHOD: Data relating to 104 patients undergoing NACT were collected. Variables derived from clinical information and pathological characteristics of patients were screened through logistic regression, random forest, and Xgboost methods to formulate predictive models. The validation and comparative assessment of these models were conducted to identify the optimal model, which was then visualized and tested. RESULT: Following the screening of variables and the establishment of multiple models based on these variables, comparative analyses were conducted using receiver operating characteristic (ROC) curves, calibration curves, as well as net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Model 2 emerged as the most optimal, incorporating variables such as HER-2, ER, T-stage, Reg IV, and Treatment, among others. The area under the ROC curve (AUC) for Model 2 in the training dataset and test dataset was 0.837 (0.734-0.941) and 0.897 (0.775-1.00), respectively. Decision curve analysis (DCA) and clinical impact curve (CIC) further underscored the potential applications of the model in guiding clinical interventions for patients. CONCLUSION: The prediction of NACT pCR efficacy based on the expression of Reg IV in breast cancer tissue appears feasible; however, it requires further validation.

Effectiveness of desertliving cistanche in managing hyperlipidemic osteoporosis in ovariectomized rats through the PI3K/AKT signaling pathway.

BACKGROUND: To aim of this study is to assess the mechanism through which Desertliving Cistanche modulates the PI3K/AKT signaling pathway in the treatment of hyperlipidemic osteoporosis in ovariectomized rats. METHODS: We randomly assigned specific-pathogen-free (SPF) rats into five groups (n = 10 per group). The normal control group received a standard diet, while the model group, atorvastatin group, diethylstilbestrol group, and treatment group were fed a high-fat diet. Four weeks later, bilateral ovariectomies were conducted, followed by drug interventions. After six weeks of treatment, relevant indicators were compared and analyzed. RESULTS: Compared to the normal control group, rats in the model group exhibited blurred trabecular morphology, disorganized osteocytes, significantly elevated levels of bone-specific alkaline phosphatase (BALP), bone Gla-protein (BGP), total cholesterol (TC), tumor necrosis factor-α (TNF-α), and receptor activator of NF-κB ligand (RANKL). Also, the model group revealed significantly reduced levels of ultimate load, fracture load, estradiol (E2), bone mineral density (BMD), osteoprotegerin (OPG), and phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in femoral tissue. The atorvastatin group presented with higher TC and TNF-α levels compared to the normal control group. Conversely, the treatment group demonstrated enhanced trabecular morphology, denser structure, smaller bone marrow cavities, and reduced BALP, BGP, TC, TNF-α, and RANKL levels. Furthermore, the treatment group exhibited higher levels of E2, BMD, OPG, and PI3K and Akt in bone tissue compared to the model group. The treatment group also had lower TC and TNF-α levels than the atorvastatin group. Biomechanical analysis indicated that after administration of Desertliving Cistanche, the treatment group had reduced body mass, increased ultimate and fracture load of the femur, denser bone structure, smaller bone marrow cavities, and altered periosteal arrangement compared to the model group. CONCLUSION: Our study revealed that Desertliving Cistanche demonstrated significant efficacy in preventing and treating postmenopausal hyperlipidemic osteoporosis in rats.

α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

DCAF7 Acts as A Scaffold to Recruit USP10 for G3BP1 Deubiquitylation and Facilitates Chemoresistance and Metastasis in Nasopharyngeal Carcinoma.

Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.

Impacts of the cyromazine emergence inhibition procedure of Bactrocera dorsalis on Fopius arisanus: implications for the biological control of diptera pest.

BACKGROUND: Fopius arisanus (Sonan) is an important egg-pupal endoparasitic wasp of Bactrocera dorsalis (Hendel). As traditional method of sorting nonparasitic B. dorsalis from parasitic wasps is labor-intensive, requires specific equipment and poses the risk of spreading fertile hosts, the development of a more convenient, economical and safe sorting procedure is important. RESULTS: The optimal cyromazine emergence inhibition procedure (CEIP) involved facilitating the pupation of B. dorsalis mature larvae (Bdml) in 3 mg kg-1 cyromazine sand substrate (CSS) for 48 h. When the Bdml that had been exposed to F. arisanus during the egg stage were treated with 3-7 mg kg-1 CSS for 48 h, no negative effects on the emergence parameters of parasitoids were observed. Treatment with 3-4 mg kg-1 CSS had insignificant effects on the biological and behavioral parameters of F. arisanus. However, treatment with 5-6 mg kg-1 CSS adversely affected the fecundity and antennating activity of the wasps; specifically, 6 mg kg-1 CSS negatively affected the lifespan and flight ability of wasps. Fortunately, no transgenerational effects on these parameters were observed in the progeny. Regarding the nutrient reserves of both sexes of F. arisanus, significant dose-dependent effects were observed. Moreover, 5-6 mg kg-1 CSS significantly reduced the protein and carbohydrate content in F. arisanus; in particular, 6 mg kg-1 CSS notably reduced the lipid content. CONCLUSION: CEIP provides a more flexible, economical and safe mass-release program for F. arisanus. In addition, it has profound implications for the biological control of other dipteran pests. © 2024 Society of Chemical Industry.

A year-long case study of multicomponent interventions to promote physical activity in office workers: A randomized control trial.

The purpose of this study was to identify if workplace interventions, (i.e., mindfulness classes and monetary incentives for gym attendance), influenced workers' physical activity. Office-based participants were randomized into one of four intervention assignments: 1) CONTROL (no interventions) (n = 40), 2) MINDFULNESS (n = 33), 3) GYM INCENTIVE (n = 41), or 4) BOTH mindfulness and gym incentive (n = 31). Activity-tracker and self-reported metabolic expenditure and step counts were gathered between January 2020 and December 2020 whereas the eight-week long interventions were provided between January and March 2020, when the impact of COVID-19 pandemic started. While physical activity decreased during the follow-up months, percent changes of physical activity at 1-, 2-, and 9-month follow-ups compared to baseline show no significant differences between or across the four intervention assignments (p > 0.05). These results suggest that the intervention assignments had no effect on physical activity from baseline. The lack of effectiveness of these interventions on participant physical activity could be attributed to the influence of the COVID-19 pandemic, and any effects of the interventions could not outweigh the effects of the pandemic.

Role of aptamer technology in extracellular vesicle biology and therapeutic applications.

Extracellular vesicles (EVs) are cell-derived nanosized membrane-bound vesicles that are important intercellular signalling regulators in local cell-to-cell and distant cell-to-tissue communication. Their inherent capacity to transverse cell membranes and transfer complex bioactive cargo reflective of their cell source, as well as their ability to be modified through various engineering and modification strategies, have attracted significant therapeutic interest. Molecular bioengineering strategies are providing a new frontier for EV-based therapy, including novel mRNA vaccines, antigen cross-presentation and immunotherapy, organ delivery and repair, and cancer immune surveillance and targeted therapeutics. The revolution of EVs, their diversity as biocarriers and their potential to contribute to intercellular communication, is well understood and appreciated but is ultimately dependent on the development of methods and techniques for their isolation, characterization and enhanced targeting. As single-stranded oligonucleotides, aptamers, also known as chemical antibodies, offer significant biological, chemical, economic, and therapeutic advantages in terms of their size, selectivity, versatility, and multifunctional programming. Their integration into the field of EVs has been contributing to the development of isolation, detection, and analysis pipelines associated with bioengineering strategies for nano-meets-molecular biology, thus translating their use for therapeutic and diagnostic utility.

Efficacy of Lactococcus lactis subsp. lactis LY-66 and Lactobacillus plantarum PL-02 in Enhancing Explosive Strength and Endurance: A Randomized, Double-Blinded Clinical Trial.

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.

The mediating effect of positive expectations in the relationship between social support and post-traumatic stress disorder symptoms among parents of children with acute lymphoblastic leukemia.

PURPOSE: Parents of children with cancer are exposed to risks of developing post-traumatic stress disorder (PTSD) symptoms, but few studies have explored PTSD symptoms of Chinese parents of children with acute lymphoblastic leukemia (ALL). Our study aimed to examine the association between social support and PTSD symptoms and to examine the mediating effect of positive expectations in this relationship among parents of children with ALL. METHODS: A cross-sectional study was conducted of consecutive parents of children with ALL in the Shengjing Hospital of China Medical University. A total of 177 parents eligible for this study completed questionnaires on PTSD symptoms, perceived social support, optimism and general self-efficacy anonymously. Asymptotic and resampling strategies were used to examine how positive expectations mediated the association between perceived social support and PTSD symptoms. RESULTS: Mean score of PTSD symptoms was 37.64 ± 14.44; 29.4% of the sample scored 44 and above, 19.8% scored 50 and above. After adjusting for covariates, perceived social support was negatively associated with the total score of PTSD symptoms (ß = -0.209, p < 0.01). Positive expectations were found to mediate the relationship between perceived social support and PTSD symptoms, especially for the symptoms of avoidance and hyperarousal. CONCLUSIONS: Optimism and general self-efficacy fully mediated the association between perceived social support and PTSD symptoms. Therefore, social support and positive expectations should be included in PTSD preventions and treatments targeting Chinese parents of children with ALL.

Digital multimeter-based portable photoelectrochemical immunoassay with enzyme-catalyzed precipitation for screening carbohydrate antigen 125.

The degree of the carbohydrate antigen 125 (CA-125) level in serum is positively correlated with the severity of ovarian cancer. In this study, a facile photoelectrochemical (PEC) immunoassay was devised for sensitive detection of CA-125 employing enzyme-catalyzed precipitation to weaken the photocurrent of hollow porous In2O3 nanotubes incorporating CdS nanoparticles. Upon the addition of the target analyte, horseradish peroxidase (HRP) enriches as a result of the formation of the sandwich immunocomplex, which can catalyze the conversion of 4-chloro1-naphthol (4-CN) to benzo-4-chlorohexadienone (4-CD) employing H2O2 as a cofactor. The as-produced insoluble precipitate acts as an obstacle to hinder the absorption of visible light by photoactive materials, thereby resulting in a decrease in photocurrent. Moreover, the weakened signal can be easily read out by a digital multimeter (DMM), advancing the convenience of the detection system. The preliminary analysis data indicate that the PEC immunoassay shows an efficient response to CA-125 levels ranging from 0.1 to 100 U mL-1 with a limit of detection (LOD) as low as 0.046 U mL-1 (S/N = 3). Most importantly, the proposed portable method has shown satisfactory performance in terms of selectivity, reproducibility, stability, and analysis in complex biological matrices.

Suicidal ideation in adolescents with adiponectin receptor 2 rs12342 polymorphism affected by Wenchuan earthquake.

PURPOSE: The present study was to investigate prevalence of suicidal ideation and its associations with biological and environmental factors in adolescents with different genotypes of rs12342 at adiponectin receptor 2 gene (ADIPOR2). METHODS: Suicidal ideation, biological and environmental factors were evaluated by questionnaires in 669 high school students after Wenchuan earthquake in China. ADIPOR2 rs12342 was genotyped by polymerase chain reaction-restriction fragment length polymorphism and verified by DNA sequencing. RESULTS: Female adolescents had higher prevalence of suicidal ideation than male students in AG heterozygote and GG homozygote, but not AA homozygote. Prevalence of suicidal ideation was different in male, but not female, subjects with different genotypes. Genotype and allele frequencies were significantly different between male students with and without suicidal ideation, but not the female counterparts. Family history of mental disorders, extent of damage to property, carbohydrate intake and protein intake were associated with suicidal ideation in female subjects, while ADIPOR2 rs12342, father's educational level and previous trauma experience were associated with suicidal ideation in male subjects. CONCLUSION: ADIPOR2 rs12342 is associated with and has potential to interact with environmental factors on suicidal ideation in a gender-dependent manner in youth. These findings pave a novel way and perspective for precision inferences of suicidal ideation in subjects with different genetic backgrounds. ADIPOR2 rs12342 needs to be considered when intervening suicidal ideation, especially in adolescents.

Regulation of Glandular Size and Phytoalexin Biosynthesis by a Negative Feedback Loop in Cotton.

Plants have evolved diverse defense mechanisms encompassing physical and chemical barriers. Cotton pigment glands are known for containing various defense metabolites, but the precise regulation of gland size to modulate defense compound levels remains enigmatic. Here, it is discovered that the VQ domain-containing protein JAVL negatively regulates pigment gland size and the biosynthesis of defense compounds, while the MYC2-like transcription factor GoPGF has the opposite effect. Notably, GoPGF directly activates the expression of JAVL, whereas JAVL suppresses GoPGF transcription, establishing a negative feedback loop that maintains the expression homeostasis between GoPGF and JAVL. Furthermore, it is observed that JAVL negatively regulates jasmonate levels by inhibiting the expression of jasmonate biosynthetic genes and interacting with GoPGF to attenuate its activation effects, thereby maintaining homeostatic regulation of jasmonate levels. The increased expression ratio of GoPGF to JAVL leads to enlarged pigment glands and elevated jasmonates and defense compounds, enhancing insect and pathogen resistance in cotton. These findings unveil a new mechanism for regulating gland size and secondary metabolites biosynthesis, providing innovative strategies for strengthening plant defense.

Forecasting the Expansion of Bactrocera tsuneonis (Miyake) (Diptera: Tephritidae) in China Using the MaxEnt Model.

The invasive pest, Bactrocera tsuneonis (Miyake), has become a significant threat to China's citrus industry. Predicting the area of potentially suitable habitats for B. tsuneonis is essential for optimizing pest control strategies that mitigate its impact on the citrus industry. Here, existing distribution data for B. tsuneonis, as well as current climate data and projections for four future periods (2021-2040, 2041-2060, 2061-2080, and 2081-2100) from the Coupled Model Intercomparison Project Phase 6 (CMIP6) were obtained. The distribution of B. tsuneonis under current and different climate change scenarios in China was predicted using the optimized MaxEnt model, ArcGIS, and the ENMeval data package. Model accuracy was assessed using ROC curves, and the primary environmental factors influencing the distribution of the pest were identified based on the percent contribution. When the regularization multiplier (RM) was set to 1.5 and the feature combination (FC) was set to LQH, a model with lower complexity was obtained. Under these parameter settings, the mean training AUC was 0.9916, and the mean testing AUC was 0.9854, indicating high predictive performance. The most influential environmental variables limiting the distribution of B. tsuneonis were the Precipitation of Warmest Quarter (Bio18) and Temperature Seasonality (standard deviation ×100) (Bio4). Under current climatic conditions, potentially suitable habitat for B. tsuneonis in China covered an area of 215.9 × 104 km2, accounting for 22.49% of the country's land area. Potentially suitable habitat was primarily concentrated in Central China, South China, and East China. However, under future climatic projections, the area of suitable habitat for B. tsuneonis exhibited varying degrees of expansion. Furthermore, the centroid of the total suitable habitat for this pest gradually shifted westward and northward. These findings suggest that B. tsuneonis will spread to northern and western regions of China under future climate changes. The results of our study indicate that climate change will have a major effect on the invasion of B. tsuneonis and have implications for the development of strategies to control the spread of B. tsuneonis in China.

Photocatalytic reduction of carbon dioxide by BiTeX (X = Cl, Br, I) under visible-light irradiation.

In this study, a series of BiTeX (X = Cl, Br, I) photocatalysts were successfully synthesized via a simple hydrothermal method. The synthesis process involved dissolving BiX3 and Te powder in toluene to identify the most efficient material for photocatalytic activity. The main objective of this approach is to facilitate the conversion of carbon dioxide into sustainable solar fuels, such as alcohols and hydrocarbons, offering an appealing solution to address environmental concerns and energy crises. The BiTeX photocatalysts demonstrated significant proficiency in converting CO2 into CH4, particularly BiTeCl exhibited a notable photocatalytic conversion rate of up to 0.51 µmolg-1h-1. The optimized BiTeX photocatalysts displayed a gradual and selective transition from CO2 to CH4, ultimately producing valuable hydrocarbons (C2+). Furthermore, owing to their ability to reduce CO2, these photocatalysts show promise as materials for mitigating environmental pollution.

A Dual-Channel Ca2+ Nanomodulator Induces Intracellular Ca2+ Disorders via Endogenous Ca2+ Redistribution for Tumor Radiosensitization.

Tumor cells harness Ca2+ to maintain cellular homeostasis and withstand external stresses from various treatments. Here, a dual-channel Ca2+ nanomodulator (CAP-P-NO) is constructed that can induce irreversible intracellular Ca2+ disorders via the redistribution of tumor-inherent Ca2+ for disrupting cellular homeostasis and thus improving tumor radiosensitivity. Stimulated by tumor-overexpressed acid and glutathione, capsaicin and nitric oxide are successively escaped from CAP-P-NO to activate the transient receptor potential cation channel subfamily V member 1 and the ryanodine receptor for the influx of extracellular Ca2+ and the release of Ca2+ in the endoplasmic reticulum, respectively. The overwhelming level of Ca2+ in tumor cells not only impairs the function of organelles but also induces widespread changes in the gene transcriptome, including the downregulation of a set of radioresistance-associated genes. Combining CAP-P-NO treatment with radiotherapy achieves a significant suppression against both pancreatic and patient-derived hepatic tumors with negligible side effects. Together, the study provides a feasible approach for inducing tumor-specific intracellular Ca2+ overload via endogenous Ca2+ redistribution and demonstrates the great potential of Ca2+ disorder therapy in enhancing the sensitivity for tumor radiotherapy.