Fine Root Traits across Different Root Orders and Their Associations with Leaf Traits in 15 Co-Occurring Plant Species from the Desert-Oasis Transition Zone in the Hexi Corridor, Gansu Province, China.

Fine root traits embody trade-offs between resource acquisition and conservation in plants. Yet, the differentiation of these traits across root orders, the existence of a root economics spectrum (RES) spanning these orders, and their linkage with leaf traits remain underexplored. In this study, we analyzed the first three root orders and leaf traits of 15 co-occurring plant species, including ten herbs and five shrubs, from the desert-oasis transition zone of the Hexi Corridor. We measured twelve morphological and chemical traits to investigate the relationships between root and leaf traits. Our results revealed significant variation in root traits both among species and within species across different root orders. We identified RES that spanned root orders, with higher-order roots exhibiting more conservative traits and lower-order roots displaying traits aligned with resource acquisition. Additionally, leaf and fine root traits showed partially decoupled adaptive strategies, yet evidence also supported the existence of a leaf economics spectrum (LES) and a potentially two-dimensional whole plant economics spectrum (WPES). Our findings suggest synergistic resource allocation strategies between fine roots and the entire plant, emphasizing the importance of root order in understanding fine root structure, function, and their interactions with other plant organs. These insights advance the understanding of fine root traits and their integration within the broader plant economics spectrum. Nevertheless, the differences in fine root traits across root orders, the presence of a root economics spectrum (RES) spanning these orders, and the relationships between fine root and leaf traits remain underexplored. We examined the first three root orders and leaves of 15 co-occurring plant species (ten herbs and five shrubs) from the desert-oasis transition zone in the Hexi Corridor, measured twelve key morphological and chemical traits. We observed substantial variation in root traits among species and root orders within species. The root economics spectrum (RES) spanned across root orders, with higher-order roots positioned at the conservative end and lower-order roots at the acquisitive end of the "investment-return" strategy axis. Leaf and fine root traits of the 15 co-occurring plant species exhibited partially decoupled adaptive strategies. However, there was also evidence for the presence of a leaf economics spectrum (LES) and a whole plant economics spectrum (WPES), with the WPES potentially being two-dimensional. Furthermore, our findings suggest synergistic resource strategies between fine roots and the whole plant. Concurrently, the significant interspecific and intraspecific differences in fine root traits, combined with the presence of a root economics spectrum across root orders, underscore the critical importance of root order in studying fine root structure, function, and their associations with other plant organs. Our findings offer valuable insights for future research on fine root traits, the RES, and their integration with the whole plant economics spectrum.

Electron beam synergetic removal of microplastics and hexavalent chromium: Synergetic removal process and mechanism.

Microplastics are ubiquitous in the environment and aged microplastics are highly susceptible to absorbing pollutants from the environment. In this study, electron beam was innovatively used to treat PVC composite Cr(VI) pollutants (Composite contaminant formed by polyvinyl chloride microplastics with the heavy metal hexavalent chromium). Experiments showed that electron beam was able to achieve synergistic removal of PVC composite Cr(VI) pollutants compared to degrading the pollutants alone. During the electron beam removal of PVC composite Cr(VI) pollutants, the reduction efficiency of Cr(VI) increased from 57% to 92%, Cl- concentration increased from 3.52 to 12.41 mg L-1, and TOC concentration increased from 16.72 to 26.60 mg L-1. The research confirmed that electron beam can effectively promote the aging degradation of PVC, alter the physicochemical properties of microplastics, and generate oxygen-containing functional groups on the surface of microplastics. Aged microplastics enhanced the adsorption capacity for Cr(VI) through electrostatic and chelation interactions, and the adsorption process followed second-order kinetics and the Freundlich model. Theoretical calculations and experiments demonstrated that PVC consumed oxidizing free radical through dechlorination and decarboxylation processes, generating inorganic ions and small organic molecules. These inorganic ions and small organic molecules further reacted with oxidizing free radical to produce reducing free radicals, facilitating the reduction of Cr(VI). Cr(VI) continuously consumed the educing free radicals to transform into Cr (Ⅲ), enhancing the system oxidative atmosphere and promoting the oxidation degradation of PVC. This study investigated the formation and synergistic removal processes of PVC composite pollutants, offering new insights for controlling microplastics composite pollution.

RBM5 induces motor neuron apoptosis in hSOD1G93A-related amyotrophic lateral sclerosis by inhibiting Rac1/AKT pathways.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder distinguished by gradual depletion of motor neurons. RNA binding motif protein 5 (RBM5), an abundantly expressed RNA-binding protein, plays a critical role in the process of cellular death. However, little is known about the role of RBM5 in the pathogenesis of ALS. Here, we found that RBM5 was upregulated in ALS hSOD1G93A-NSC34 cell models and hSOD1G93A mice due to a reduction of miR-141-5p. The upregulation of RBM5 increased the apoptosis of motor neurons by inhibiting Rac1-mediated neuroprotection. In contrast, genetic knockdown of RBM5 rescued motor neurons from hSOD1G93A-induced degeneration by activating Rac1 signaling. The neuroprotective effect of RBM5-knockdown was significantly inhibited by the Rac1 inhibitor, NSC23766. These findings suggest that RBM5 could potentially serve as a therapeutic target in ALS by activating the Rac1 signalling.

Nanoparticle-Based Drug Delivery Systems for Inflammatory Bowel Disease Treatment.

Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory condition characterized by recurring inflammation of the intestinal mucosa. However, the existing IBD treatments are ineffective and have serious side effects. The etiology of IBD is multifactorial and encompasses immune, genetic, environmental, dietary, and microbial factors. The nanoparticles (NPs) developed based on specific targeting methodologies exhibit great potential as nanotechnology advances. Nanoparticles are defined as particles between 1 and 100 nm in size. Depending on their size and surface functionality, NPs exhibit different properties. A variety of nanoparticle types have been employed as drug carriers for the treatment of inflammatory bowel disease (IBD), with encouraging outcomes observed in experimental models. They increase the bioavailability of drugs and enable targeted drug delivery, promoting localized treatment and thus enhancing efficacy. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines.

Revealing the role of interlayer spacing in radioactive-ion sieving of functionalized graphene membranes.

Functionalization of graphene enables precise control over interlayer spacing during film formation, thereby enhancing the separation efficiency of radioactive ions in graphene membranes. However, the systematic impact of interlayer spacing of graphene membranes on radioactive-ion separation remains unexplored. This study aims to elucidate how interlayer spacing in functionalized graphene membranes affects the separation of radioactive ions. Utilizing polyamidoxime (PAO) to modify graphene oxide, we controlled the interlayer spacing of graphene membranes. Experimental results indicate that tuning interlayer spacing enables control of the permeation flux of radioactive ions (UO22+ 1.01 × 10-5-8.32 × 10-5 mol/m2·h, and K+ remains stable at 3.60 × 10-4 mol/m2·h), and the K+/UO22+ separation factors up to 36.2 at an interlayer spacing of 8.8 Å. Using density functional theory and molecular dynamics simulations, we discovered that the effective separation is mainly determined via interlayer spacing and the quantity of introduced functional groups, explaining the anomalous high permeation flux of target ions at low interlayer spacing (4.3 Å). This study deepens our comprehension of interlayer spacing within nanoconfined spaces for ion separation and recovery via graphene membranes, offering valuable insights for the design and synthesis of high-performance nanomembrane materials.

Enabling Gradient-Structured Solid Electrolyte Interphase by a Hydrated Eutectic Electrolyte for High-Performance Zn Metal Batteries.

Aqueous Zn metal batteries are attracting tremendous interest as promising energy storage systems due to their intrinsic safety and cost-effectiveness. Nevertheless, the reversibility of Zn metal anodes (ZMAs) is hindered by water-induced parasitic reactions and dendrite growth. Herein, a novel hydrated eutectic electrolyte (HEE) consisting of Zn(BF4)2·xH2O and sulfolane (SL) is developed to prevent the side reactions and achieve the outstanding cyclability of ZMAs. The strong coordination between Zn2+ and SL triggers the eutectic feature, enabling the low-temperature availability of HEEs. The restriction of BF4 - hydrolysis in the eutectic system can realize favorable compatibility between Zn(BF4)2-based electrolyte and ZMAs. Besides, the newly-established solvation structure with the participation of SL, H2O, and BF4 -, can induce in situ formation of desirable SEI with gradient structure consisting of B,O-rich species, ZnS, and ZnF2, to offer satisfactory protection toward ZMAs. Consequently, the HEE allows the Zn||Zn symmetric cell to cycle over 1650 h at 2 mA cm-2 and 1 mA h cm-2. Moreover, the Zn||NH4V4O10 full batteries can deliver a prolonged lifespan for 1000 cycles with a high capacity retention of 83.4%. This work represents a feasible approach toward the elaborate design of advanced electrolyte systems for next-generation batteries.

A massive pulmonary arteriovenous fistula complicated with coronary atherosclerotic heart disease treated by interventional therapy: a case report.

BACKGROUND: Pulmonary arteriovenous fistula (PAVF) is a rare disease, and its symptoms lack specificity. For patients with coronary heart disease(CHD), hypertension and other common cardiovascular diseases, PAVF is easy to be ignored. We presented a case of massive PAVF complicated with coronary atherosclerotic heart disease by interventional treatment to improve the understanding of this complex disease. CASE PRESENTATION: A 77-year-old female patient was admitted to the hospital due to chest tightness and shortness of breath following activities, which was diagnosed with CHD and hypoxemia in other hospitals. Coronary angiography showed that the patient had severe stenosis of coronary artery while pulmonary vascular DSA showing the patient had PAVF. After interventional therapy of both coronary artery and PAVF, the patient's symptoms were significantly improved. CONCLUSION: We presented a case of massive PAVF complicated with CHD by interventional treatment. For patients with unexplained hypoxemia and symptoms similar with CHD, the possibility of PAVF often leads to oversight, and various auxiliary examinations should be improved to avoid missed diagnosis. And intervention treatment should be carried out to improve the prognosis of patients as much as possible.

Investigation into the characteristics of electron beam-aged microplastics and adsorption behavior of dibutyl phthalate.

Microplastics are increasingly prevalent in the environment, and their ability to adsorb various organic additives, posing harm to organisms, has attracted growing attention. Currently, there are no effective methods to age microplastics, and there is limited discussion on the subsequent treatment of aged microplastics. This study focuses on micro polyethylene (PE) and employs electron beam technology for aging treatment, investigating the adsorption and leaching behavior between PE and dibutyl phthalate (DBP) before and after aging. Experimental results indicate that with increasing doses of electron beam irradiation, the surface microstructure of PE worsens, inducing the generation of oxygen-containing functional groups on the surface of polyethylene. Comparative evaluations between electron beam aging and existing methods show that electron beam technology surpasses existing aging methods, achieving a level of aging exceeding 0.7 within an extremely short period of 1 min at doses exceeding 350 kGy. Adsorption experiments demonstrate that the adsorption between PE and DBP conforms to pseudo-second-order kinetics and the Freundlich model both before and after aging. The adsorption capacity of microplastics for DBP increases from 76.8 mg g-1 to 167.0 mg g-1 after treatment, exceeding that of conventional DBP adsorbents. Electron beam irradiation causes aging of microplastics mainly through the generation of ·OH, which lead to the formation of oxygen-containing functional groups on the microplastics' surface, thereby enhancing their adsorption capacity for DBP. This provides a new perspective for the degradation of aged microplastics and composite pollutants.

Stable anode/separator interface enabled by graft modification of polypropylene separator via electron beam irradiation technique toward high-performance sodium metal batteries.

Sodium metal batteries (SMBs) are considered as strong alternatives to lithium-ion batteries (LIBs), due to the inherent merits of sodium metal anodes (SMAs) including low redox potential (-2.71 V vs. SHE), high theoretical capacity (1166 mAh g-1), and abundant resources. However, the uncontrollable Na dendrite growth has significantly impeded the practical deployment of SMBs. Separator modification has emerged as an effective strategy for substantially enhancing the performance of SMAs. Herein, for the first time, we present the successful grafting polyacrylic acid (PAA) onto polypropylene (PP) separators (denoted as PP-g-PAA) using highly efficient electron beam (EB) irradiation to improve the cyclability of SMAs. The polar carboxyl groups of PAA can facilitate the electrolyte wetting and provide ample mechanical strength to resist dendrite penetration. Consequently, the regulation of Na+ ion flux enables uniform Na+ deposition with dendrite-free morphology, facilitated by the favorable anode/separator interface. The PP-g-PAA separator significantly enhances the cyclability of fabricated cells. Notably, the lifespan of Na||Na symmetric cells can be extended up to 5519 h at 1 mA cm-2 and 1 mAh cm-2. The stable design of the anode/separator interface achieved through polyolefin separator modification presented in this study holds promise for the further advancement of next-generation advanced battery systems.

A Cuproptosis-Related gene Signature as a Prognostic Biomarker in Thyroid Cancer Based on Transcriptomics.

Thyroid cancer (THCA) is the most prevalent endocrine tumor, and its incidence continues to increase every year. However, the processes underlying the aggressive progression of thyroid cancer are unknown. We concentrated on the prognostic and biological importance of thyroid cancer cuproptosis-related genes in this investigation. Genomic and clinical data were obtained from the UCSC XENA website, and cuproptosis-related genes were obtained from the FerrDb website. We performed differential expression analysis and Cox regression analysis to identify possible predictive targets associated with thyroid cancer prognosis. To assess the role of CDKN2A in thyroid cancer and the ability to predict prognosis on the basis of the CDKN2A expression level, we performed immunohistochemical staining, survival analysis, immunological analysis, functional analysis, and clinical analysis with respect to CDKN2A gene expression. CDKN2A expression levels were found to be inversely correlated with thyroid cancer prognosis. Higher levels of CDKN2A expression were associated with higher T, N, and clinicopathological stage and more residual tumor cells. Through univariate and multivariate Cox regression analyses, the CDKN2A expression level was shown to be linked with thyroid cancer patients' overall survival (OS). Moreover, we discovered that CDKN2A expression was linked to a dysfunctional tumor immune microenvironment. The study shows that CDKN2A, a cuproptosis-related gene, can be used as a prognostic marker for thyroid cancer.

ß-Galactosidase-guided self-assembled 68Ga nanofibers probe for micro-PET tumor imaging.

ß-galactosidase (ß-gal) has high activity in various malignancies, which is suitable for targeted positron emission tomography (PET) imaging. Meanwhile, ß-gal can successfully guide the formation of nanofibers, which enhances the intensity of imaging and extends the imaging time. Herein, we designed a ß-galactosidase-guided self-assembled PET imaging probe [68Ga]Nap-NOTA-1Gal. We envisage that ß-gal could recognize and cleave the target site, bringing about self-assembling to form nanofibers, thereby enhancing the PET imaging effect. The targeting specificity of [68Ga]Nap-NOTA-1Gal for detecting ß-gal activity was examined using the control probe [68Ga]Nap-NOTA-1. Micro-PET imaging showed that tumor regions of [68Ga]Nap-NOTA-1Gal were visible after injection. And the tumor uptake of [68Ga]Nap-NOTA-1Gal was higher than [68Ga]Nap-NOTA-1 at all-time points. Our results demonstrated that the [68Ga]Nap-NOTA-1Gal can be used for the purpose of a new promising PET probe for helping diagnose cancer with high levels of ß-gal activity.

Construction of unique NiCoP/FeNiCoP hollow heterostructured ellipsoids with modulated electronic structure for enhanced overall water splitting.

Transition metal phosphides have been demonstrated to be promising non-noble catalysts for water splitting, yet their electrocatalytic performance is impeded by unfavorable free energies of adsorbed intermediates. The achievement of nanoscale modulation in morphology and electronic states is imperative for enhancing their intrinsic electrocatalytic activity. Herein, we propose a strategy to expedite the water splitting process over NiCoP/FeNiCoP hollow ellipsoids by modulating the electronic structure and d-band center. These unique phosphorus (P) vacancies-rich ellipsoids are synthesized through an ion-exchange reaction between uniform NiCo-nanoprisms and K3[Fe(CN)6], followed by NaH2PO2-assisted phosphorization under N2 atmosphere. Various characterizations reveals that the titled catalyst possesses high specific surface area, abundant porosity, and accessible inner surfaces, all of which are beneficial for efficient mass transfer and gas diffusion. Moreover, density functional theory (DFT) calculations further confirms that the NiCoP/FeNiCoP heterojunction associated with P vacancies regulate the electronic structures of d-electrons and p-electrons of Co and P atoms, respectively, resulting in a higher desorption efficiency of adsorbed H* intermediates with a lower energy barrier for water splitting. Due to the aforementioned advantages, the resultant NiCoP/FeNiCoP hollow ellipsoids exhibit remarkably low overpotentials of 45 and 266 mV for hydrogen and oxygen evolution reaction to achieve the current densities of 10 and 50 mA cm-2, respectively. This work not only reports the synthesis of a hollow double-shell structure of NiCoP/FeNiCoP but also introduces a novel strategy for constructing a multifunctional electrocatalyst for water splitting.

Failure of lipid control by PCSK9 inhibitors in compound heterozygous familial hypercholesterolemia complicated with premature myocardial infarction: A case report.

Key Clinical Message: A certain level of low-density lipoprotein receptor activity is crucial for the efficacy of PCSK9i. Therapeutic strategies for familial hypercholesterolemia patients should consider drug efficacy, and genetic testing will be helpful. Abstract: Familial hypercholesterolemia (FH) is a serious autosomal dominant disorder. Managing blood lipids in FH patients poses greater challenges for clinicians. Drug therapy may not always yield satisfactory results, particularly in individuals with low-density lipoprotein receptor (LDLR) negative mutations. Herein, we report a young female harboring an LDLR frameshift mutation. This patient developed xanthomas at 7 months old and underwent several years of treatment involving four classes of lipid-lowering drugs, including PCSK9i. However, the response to drug therapy was limited in this patient and eventually culminated in premature myocardial infarction. The efficacy of PCSK9i depends on the activity of LDLR. The inefficacy of PCSK9i may arise from the extensive mutations which leading to loss of LDLR activity. Therapy plans for these patients should take into account the efficacy of drug therapy. Early genetic testing is crucial for clinicians to make informed decisions regarding therapy options.

The chief culprit of intractable hypoxemia: a case report of rare pulmonary arteriovenous fistula complicated with giant hemangioma.

BACKGROUND: Pulmonary arteriovenous fistula (PAVF) is a rare disease, which can lead to the direct return of unoxidized venous blood to pulmonary veins and left heart, resulting in right-to-left shunt leading to hypoxia. Long term, the right-to-left shunt will cause severe pathophysiological changes in the patient's body and pulmonary circulation, and the prognosis will be poor if PAVF is not treated timely. CASE PRESENTATION: Here, we report the case of a 71-year-old man who presented with chest tightness and shortness of breath. After a series of examinations, PAVF and giant hemangioma were diagnosed, which are difficult to operate.Transcatheter interventional therapy was initiated. The patient recovered on the third day after operation and was discharged smoothly. During the long-term follow-up of nearly 4 years after discharge, the general condition and quality of life of the patient basically returned to normal. CONCLUSIONS: PAVF is rare but very important clinical problem. When the clinical manifestations of persistent unexplained hypoxia appear, it is necessary to fully consider the possibility of PAVF. Once the diagnosis of PAVF is clear, timely treatment is recommended to avoid deterioration of the disease and affecting the prognosis.

Investigation of the adsorption behavior and adsorption mechanism of pollutants onto electron beam-aged microplastics.

Microplastics, as an emerging pollutant, are widely distributed worldwide. Extensive research has been conducted to address the issue of microplastic pollution; however, effective methods for microplastic treatment are still lacking. This study innovatively utilizes electron beam technology to age and degrade microplastics. Compared to other treatment methods, electron beam technology can effectively promote the aging and degradation of microplastics. The Oxygen - carbon ratio of aged microplastics reached 0.071, with a mass loss of 48 % and a carbonyl index value of 0.69, making it the most effective method for short-term aging treatment in current research efforts. Theoretical calculations and experimental results demonstrate that a large number of oxygen-containing functional groups are generated on the surface of microplastics after electron beam irradiation, changing their adsorption performance for pollutants. Theoretical calculations show that an increase in oxygen-containing functional groups on the surface leads to a gradual decrease in hydrophobic pollutant adsorption capacity while increasing hydrophilic pollutant adsorption capacity for aged microplastics. Experimental studies were conducted to investigate the adsorption behavior and process of typical pollutants by aged microplastics which conform to pseudo-second-order kinetics and Henry model during the adsorption process, and the adsorption results are consistent with theoretical calculations. The results show that the degradation of microplastics is mainly due to hydroxyl radicals generated by electron beam irradiation, which can break the carbon chain of microplastics and gradually degrade them into small molecular esters and alcohols. Furthermore, studies have shown that microplastics can desorb pollutants in pure water and simulated gastric fluid. Overall, electron beam irradiation is currently the most effective method for degrading microplastics. These results also clearly elucidate the characteristics and mechanisms of the interaction between aged microplastics and organic pollutants, providing further insights for assessing microplastic pollution in real-world environments.

Roflupram alleviates autophagy defects and reduces mutant hSOD1-induced motor neuron damage in cell and mouse models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable disease involving motor neuron (MN) degeneration and is characterized by ongoing myasthenia and amyotrophia in adults. Most ALS patients die of respiratory muscle paralysis after an average of 3-5 years. Defective autophagy in MNs is considered an important trigger of ALS pathogenesis. Roflupram (ROF) was demonstrated to activate autophagy in microglial cells and exert protective effects against Parkinson's disease (PD) and Alzheimer's disease (AD). Therefore, our research aimed to investigate the efficacy and mechanism of ROF in treating ALS both in vivo and in vitro. We found that ROF could delay disease onset and prolong the survival of hSOD1-G93A transgenic mice. Moreover, ROF protected MNs in the anterior horn of the spinal cord, activated the AMPK/ULK1 signaling pathway, increased autophagic flow, and reduced SOD1 aggregation. In an NSC34 cell line stably transfected with hSOD1-G93A, ROF protected against cellular damage caused by hSOD1-G93A. Moreover, we have demonstrated that ROF inhibited gliosis in ALS model mice. Collectively, our study suggested that ROF is neuroprotective in ALS models and the AMPK/ULK1 signaling pathway is a potential therapeutic target in ALS, which increases autophagic flow and reduces SOD1 aggregation.

Assessing Global, Regional, and National Time Trends and Associated Risk Factors of the Mortality in Ischemic Heart Disease Through Global Burden of Disease 2019 Study: Population-Based Study.

BACKGROUND: Ischemic heart disease (IHD) is the leading cause of death among noncommunicable diseases worldwide, but data on current epidemiological patterns and associated risk factors are lacking. OBJECTIVE: This study assessed the global, regional, and national trends in IHD mortality and attributable risks since 1990. METHODS: Mortality data were obtained from the Global Burden of Disease 2019 Study. We used an age-period-cohort model to calculate longitudinal age curves (expected longitudinal age-specific rate), net drift (overall annual percentage change), and local drift (annual percentage change in each age group) from 15 to >95 years of age and estimate cohort and period effects between 1990 and 2019. Deaths from IHD attributable to each risk factor were estimated on the basis of risk exposure, relative risks, and theoretical minimum risk exposure level. RESULTS: IHD is the leading cause of death in noncommunicable disease-related mortality (118.1/598.8, 19.7%). However, the age-standardized mortality rate for IHD decreased by 30.8% (95% CI -34.83% to -27.17%) over the past 30 years, and its net drift ranged from -2.89% (95% CI -3.07% to -2.71%) in high sociodemographic index (SDI) region to -0.24% (95% CI -0.32% to -0.16%) in low-middle-SDI region. The greatest decrease in IHD mortality occurred in the Republic of Korea (high SDI) with net drift -6.06% (95% CI -6.23% to -5.88%), followed by 5 high-SDI nations (Denmark, Norway, Estonia, the Netherlands, and Ireland) and 2 high-middle-SDI nations (Israel and Bahrain) with net drift less than -5.00%. Globally, age groups of >60 years continued to have the largest proportion of IHD-related mortality, with slightly higher mortality in male than female group. For period and birth cohort effects, the trend of rate ratios for IHD mortality declined across successive period groups from 2000 to 2004 and birth cohort groups from 1985 to 2000, with noticeable improvements in high-SDI regions. In low-SDI regions, IHD mortality significantly declined in female group but fluctuated in male group across successive periods; sex differences were greater in those born after 1945 in middle- and low-middle-SDI regions and after 1970 in low-SDI regions. Metabolic risks were the leading cause of mortality from IHD worldwide in 2019. Moreover, smoking, particulate matter pollution, and dietary risks were also important risk factors, increasingly occurring at a younger age. Diets low in whole grains and legumes were prominent dietary risks in both male and female groups, and smoking and high-sodium diet mainly affect male group. CONCLUSIONS: IHD, a major concern, needs focused health care attention, especially for older male individuals and those in low-SDI regions. Metabolic risks should be prioritized for prevention, and behavioral and environmental risks should attract more attention to decrease IHD mortality.

ß-aminoisobutyrics acid, a metabolite of BCAA, activates the AMPK/Nrf-2 pathway to prevent ferroptosis and ameliorates lung ischemia-reperfusion injury.

BACKGROUND: Lung ischemia-reperfusion (I/R) injury is a serious clinical problem without effective treatment. Enhancing branched-chain amino acids (BCAA) metabolism can protect against cardiac I/R injury, which may be related to bioactive molecules generated by BCAA metabolites. L-ß-aminoisobutyric acid (L-BAIBA), a metabolite of BCAA, has multi-organ protective effects, but whether it protects against lung I/R injury is unclear. METHODS: To assess the protective effect of L-BAIBA against lung I/R injury, an animal model was generated by clamping the hilum of the left lung, followed by releasing the clamp in C57BL/6 mice. Mice with lung I/R injury were pre-treated or post-treated with L-BAIBA (150 mg/kg/day), given by gavage or intraperitoneal injection. Lung injury was assessed by measuring lung edema and analyzing blood gases. Inflammation was assessed by measuring proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), and neutrophil infiltration of the lung was measured by myeloperoxidase activity. Molecular biological methods, including western blot and immunofluorescence, were used to detect potential signaling mechanisms in A549 and BEAS-2B cells. RESULTS: We found that L-BAIBA can protect the lung from I/R injury by inhibiting ferroptosis, which depends on the up-regulation of the expressions of GPX4 and SLC7A11 in C57BL/6 mice. Additionally, we demonstrated that the Nrf-2 signaling pathway is key to the inhibitory effect of L-BAIBA on ferroptosis in A549 and BEAS-2B cells. L-BAIBA can induce the nuclear translocation of Nrf-2. Interfering with the expression of Nrf-2 eliminated the protective effect of L-BAIBA on ferroptosis. A screening of potential signaling pathways revealed that L-BAIBA can increase the phosphorylation of AMPK, and compound C can block the Nrf-2 nuclear translocation induced by L-BAIBA. The presence of compound C also blocked the protective effects of L-BAIBA on lung I/R injury in C57BL/6 mice. CONCLUSIONS: Our study showed that L-BAIBA protects against lung I/R injury via the AMPK/Nrf-2 signaling pathway, which could be a therapeutic target.

L-BAIBA upregulates the expression of GPX4 and SLC7A11 by activating the AMPK/Nrf-2/GPX4/SLC7A11 signaling pathway, thereby protecting against I/R-induced increase in ROS and ferroptosis in the lung.

Researches of calcium-activated chloride channel ANO1 intervening amyotrophic lateral sclerosis progression by activating EGFR and CaMKII signaling.

BACKGROUND: ANO1 is closely correlated with the activation of EGFR and CaMKII, while EGFR and CaMKII show low activation in amyotrophic lateral sclerosis (ALS) models. Therefore, we designed experiments to verify that ANO1 may play a protective role on motor neurons in ALS by activating EGFR and CaMKII. METHODS: The expression changes of ANO1, EGFR, CaMKII, pEGFR, and pCaMKII, cell survival status, and apoptosis were studied by western blot, real-time quantitative PCR, immunofluorescence, immunohistochemistry, CCK-8, and flow cytometry. The role of ANO1 in the ALS model by activating EGFR and CaMKII was studied by applying corresponding activators, inhibitors, gene silencing, and overexpression. RESULTS: In hSOD1G93A transgenic animals and cell lines, low expression of ANO1 and low activation of EGFR and CaMKII were identified. ANO1 expression decreased gradually with the progression of ALS. Overexpression of ANO1 in the hSOD1G93A cell line and primary neurons of hSOD1G93A transgenic mice increased cell viability and decreased cell apoptosis. After the application of ANO1 inhibitor CaCC-inhA01 in hSOD1G93A cell line and primary neurons of hSOD1G93A transgenic mice, EGFR activator EGF and CaMKII activator Carbachol, increased cell viability and reduced cell apoptosis. After ANO1 was overexpressed in the hSOD1G93A cell line and primary neurons of hSOD1G93A transgenic mice, EGFR inhibitor AEE788 and CaMKII inhibitor KN93 decreased cell viability and increased cell apoptosis. CONCLUSIONS: Our results suggest that ANO1 plays an important role in the survival of ALS motor neurons. ANO1 can increase cell activity and reduce apoptosis by activating EGFR and CaMKII signals.

Synthesis and preliminary biological evaluation of a novel 99mTc-labeled small molecule for PD-L1 imaging.

In recent years, PD-1/PD-L1 checkpoint blockade immunotherapy with remarkable efficacy has set off a heat wave. The expression level of PD-L1, which plays a predictive role in anti-PD-1/PD-L1 therapy, could be quantified by noninvasive imaging with radiotracers. Herein, we introduced the synthesis and preliminary biological evaluation of a novel 99mTc-labeled small molecule radiotracer [99mTc]G3C-CBM for PD-L1 imaging. [99mTc]G3C-CBM was achieved with high radiochemical purity (>96 %) and remained good stability in PBS and FBS. In competitive combination experiment, [99mTc]G3C-CBM was displaced by increasing concentrations of unlabeled G3C-CBM, resulting in an IC50 value of 41.25±2.23 nM for G3C-CBM. The uptake of [99mTc]G3C-CBM in A375-hPD-L1 cells (17.51±2.08 %) was approximately 6.47 folds of that in A375 cells (2.71±0.36 %) after co-incubation for 2 h. The biodistribution results showed that the radioactivity uptake in A375-hPD-L1 tumor reached the maximum (0.35±0.01 %ID/g) at 2 h post injection, and the optimum tumor/muscle ratio of 2.94±0.29 occurred at the same time. In addition, [99mTc]G3C-CBM was quickly cleared from the blood with a clearance half-life of just 119.25 min. These results indicate that [99mTc]G3C-CBM is a potential SPECT PD-L1 imaging agent and is worthy of further study.