Adverse events and efficacy of second-round CAR-T cell therapy in relapsed pediatric B-ALL.

OBJECTIVE: Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment approach for pediatric patients suffering from relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, there was a paucity of data on the challenges associated with second-round CAR-T therapy in this population. METHODS: Medical records of nine pediatric patients who received second-round CAR-T therapy in a single center from June 2019 to May 2023 were analyzed. Throughout the course of the clinical trial, we evaluated adverse events including CRS, CRES, infections, hematologic toxicity, and organ injury, as well as CAR-T responses. RESULTS: Except for one patient who chose CART therapy due to testicular relapse, the remaining patients had indications for CAR-T therapy due to relapse with bone marrow alone or combined with other site. There were no difference between the transfusion dose of CART1 and CART2. No differences of incidence and grade of CRS was found between the first-round CAR-T therapy (CART1) and second-round CAR-T therapy (CART2). Additionally, we found that the incidence of CRES was higher for CART1(3/9,33.3%) than CART2(1/9,11.1%). Our findings revealed that there were no differences of IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α between CART1 and CART2, but the peak level of IL-17A was significantly higher in patients receiving CART1 compared to those receiving CART2 (p = .011). Early and late infection rates after CART1 were higher than CART2. Based on the dynamic changes of ANC, hemoglobin and platelet, ANC, and platelet were reduced obviously post CART. It seems that the incidences of severe thrombocytopenia and severe anemia were higher in the CART1 group compared to CART2. The MRD-negative CR rates for CART1 and CART2 are 100% and 44.4%, respectively (p = .029). All patients experienced events (relapse, chemotherapy, transplantation, or death) after receiving CART2, including one died, three discharged automatically, and the remaining five patients survived. CONCLUSION: Although the remission rate of CART2 is not as high as the CART1 due to the severity of the disease, its safety regarding CRS, CRES, infections, and organ injury is still excellent. Therefore, CART2 remains a viable option for treating pediatric relapsed B-ALL.

Pterostilbene-Loaded Soluplus/Poloxamer 188 Mixed Micelles for Protection against Acetaminophen-Induced Acute Liver Injury.

Excessive acetaminophen (APAP) induces excess reactive oxygen species (ROS), leading to liver damage. Pterostilbene (PTE) has excellent antioxidant and anti-inflammatory activities, but poor solubility limits its biological activity. In this study, we prepared PTE-loaded Soluplus/poloxamer 188 mixed micelles (PTE-MMs), and the protective mechanism against APAP-induced liver injury was investigated. In vitro results showed that PTE-MMs protected H2O2-induced HepG2 cell proliferation inhibition, ROS accumulation, and mitochondrial membrane potential destruction. Immunofluorescence results indicated that PTE-MMs significantly inhibited H2O2-induced DNA damage and cGAS-STING pathway activation. For in vivo protection studies, PTE-MMs (25 and 50 mg/kg) were administered orally for 5 days, followed by APAP (300 mg/kg). The results showed that APAP significantly induced injury in liver histopathology as well as an increase in serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, the above characteristics of APAP-induced acute liver injury were inhibited by PTE-MMs. In addition, APAP-induced changes in the activities of antioxidant enzymes such as SOD and GSH in liver tissue were also inhibited by PTE-MMs. Immunohistochemical results showed that PTE-MMs inhibited APAP-induced DNA damage and cGAS-STING pathway activation in liver tissues. For in vivo therapeutic effect study, mice were first given APAP (300 mg/kg), followed by oral administration of PTE-MMs (50 mg/kg) for 3 days. The results showed that PTE-MMs exhibited promising therapeutic effects on APAP-induced acute liver injury. In conclusion, our study shows that the Soluplus/poloxamer 188 MM system has the potential to enhance the biological activity of PTE in the protection and therapeutic of liver injury.

Myricetin-Loaded Nanomicelles Protect against Cisplatin-Induced Acute Kidney Injury by Inhibiting the DNA Damage-cGAS-STING Signaling Pathway.

Acute kidney injury (AKI) is the most common side effect of the anti-cancer drug cisplatin, and currently, no effective preventive measures are available in clinical practice. Oxidative stress and DNA damage mechanisms may be involved in cisplatin-induced AKI. In this study, we prepared Kolliphor HS15-based myricetin-loaded (HS15-Myr) nanomicelles and explored the mechanism of protection against cisplatin-induced AKI. In vitro results showed that the HS15-Myr nanomicelles enhanced the antioxidant activity of myricetin (Myr) and inhibited cisplatin-induced proliferation inhibition of HK-2 cells. Moreover, the HS15-Myr nanomicelles inhibited cisplatin-induced reactive oxygen species accumulation, mitochondrial membrane potential reduction, and DNA damage, which might be related to the inhibition of the cyclic GMP-AMP synthase (cGAS)─stimulating interferon gene (STING) signaling pathway. In vivo results in mice showed that the significant reductions in body weight and renal indices and the increased blood urea nitrogen and serum creatinine levels induced by cisplatin could be significantly reversed by pretreating with the HS15-Myr nanomicelles. Furthermore, nanomicelle pretreatment significantly altered the activities of antioxidant enzymes (e.g., GSH, MDA, and SOD) induced by cisplatin. In addition, cisplatin-induced inflammatory responses in mouse kidney tissue were found to be inhibited by pretreatment with HS15-Myr nanomicelles, such as IL-1ß and TNF-α expression. The nanomicelles also significantly inhibited cisplatin-induced activation of the DNA damage-cGAS-STING pathway in kidney tissues. Together, our findings suggest that Myr-loaded nanomicelles are potential nephroprotective drugs.

Efficacy of Hemoperfusion Cartridge Procedure on Patients Undergoing Cardiac Valve Replacement Surgery with Cardiopulmonary Bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) induces inflammatory homeostasis dysregulation, closely related to many postoperative adverse effects. Minimizing the systemic inflammatory response to CPB is imperative to improving cardiac surgery safety. This study aimed to retrospectively evaluate the efficacy of the hemoperfusion cartridge, a device recently designed for extracorporeal blood purification to remove cytokines from the blood for patients undergoing cardiac valve replacement surgery using CPB. METHODS: The hemoperfusion (HP) group consisted of 138 patients, who underwent a hemoperfusion cartridge procedure during CPB. The control group included 149 patients, who received standard CPB management. The evaluated indices included inflammatory cytokines, blood biochemical indices, and postoperative outcome indices. RESULTS: Patients in the HP group had relatively lower interleukin (IL)-6 levels (days one and two post-CPB) and IL-8 (day one post-CPB) compared with the control group. Some relatively decreased biochemical blood indices also were observed in the HP group, including a significantly lower lactic acid level (days one, two, and three post-CPB), platelet counts (days one, two, and three post-CPB), and aspartate aminotransferase (days one and three post-CPB). Regarding the postoperative outcomes, no severe complications occurred in the patients; however, the HP group required less ventilation time than the control group. CONCLUSIONS: The hemoperfusion cartridge seems promising in limiting the inflammatory reactions during CPB, with noteworthy potential for application in cardiac surgery.

Characterization, reactivity, source apportionment, and potential source areas of ambient volatile organic compounds in a typical tropical city.

Based on one-year observation, the concentration, sources, and potential source areas of volatile organic compounds (VOCs) were comprehensively analyzed to investigate the pollution characteristics of ambient VOCs in Haikou, China. The results showed that the annual average concentration of total VOCs (TVOCs) was 11.4 ppbV, and the composition was dominated by alkanes (8.2 ppbV, 71.4%) and alkenes (1.3 ppbV, 20.5%). The diurnal variation in the concentration of dominant VOC species showed a distinct bimodal distribution with peaks in the morning and evening. The greatest contribution to ozone formation potential (OFP) was made by alkenes (51.6%), followed by alkanes (27.2%). The concentrations of VOCs and nitrogen dioxide (NO2) in spring and summer were low, and it was difficult to generate high ozone (O3) concentrations through photochemical reactions. The significant increase in O3 concentrations in autumn and winter was mainly related to the transmission of pollutants from the northeast. Traffic sources (40.1%), industrial sources (19.4%), combustion sources (18.6%), solvent usage sources (15.5%) and plant sources (6.4%) were identified as major sources of VOCs through the positive matrix factorization (PMF) model. The southeastern coastal areas of China were identified as major potential source areas of VOCs through the potential source contribution function (PSCF) and concentration-weighted trajectory (CWT) models. Overall, the concentration of ambient VOCs in Haikou was strongly influenced by traffic sources and long-distance transport, and the control of VOCs emitted from vehicles should be strengthened to reduce the active species of ambient VOCs in Haikou, thereby reducing the generation of O3.

Development of quercetin-loaded PVCL-PVA-PEG micelles and application in inhibiting tumor angiogenesis through the PI3K/Akt/VEGF pathway.

Quercetin (Que) exhibits excellent biological activity; however, its clinical development is hindered owing to the poor water solubility. In this study, Que. was loaded on polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG, Soluplus) micelles through a thin-film hydration process, and their tumor angiogenesis inhibition ability was investigated. The particle size of Soluplus-Que micelles was 55.3 ± 1.8 nm, and the micelles stayed stability within 9 months. Soluplus-Que micelles can enhance the cell uptake of Que. and transport the micelles to intracellular lysosomes and mitochondria. The MTT assay results revealed that Soluplus-Que micelles enhanced the cytotoxicity of Que. on HUVEC cells. Furthermore, Soluplus-Que micelles inhibited migration and invasion of HUVEC cells, as well as inhibited the neovascularization of chick embryo allantoic membrane (CAM). The in vivo study revealed that Soluplus-Que micelles significantly inhibit the growth of H22 solid tumors, with low toxic side effects. Soluplus-Que inhibited the expression of CD31 (a marker of angiogenesis) and the PI3K/Akt/VEGF pathway in tumor tissues, indicating its potential to hold back tumor growth via the inhibition of angiogenesis. Our findings indicated that as a delivery system, Soluplus micelles demonstrate potential for the delivery of poorly soluble drugs for tumor treatment.

Realizing the values of natural capital for inclusive, sustainable development: Informing China's new ecological development strategy.

A major challenge in transforming development to inclusive, sustainable pathways is the pervasive and persistent trade-off between provisioning services (e.g., agricultural production) on the one hand and regulating services (e.g., water purification, flood control) and biodiversity conservation on the other. We report on an application of China's new Ecological Development Strategy, now being formally tested and refined for subsequent scaling nationwide, which aims to mitigate and even eliminate these trade-offs. Our focus is the Ecosystem Function Conservation Area of Hainan Island, a rural, tropical region where expansion of rubber plantations has driven extensive loss of natural forest and its vital benefits to people. We explored both the biophysical and the socioeconomic options for achieving simultaneous improvements in product provision, regulating services, biodiversity, and livelihoods. We quantified historic trade-offs between rubber production and vital regulating services, finding that, over the past 20 y (1998-2017), there was a 72.2% increase in rubber plantation area, leading to decreases in soil retention (17.8%), water purification [reduced retention of nitrogen (56.3%) and phosphorus (27.4%)], flood mitigation (21.9%), carbon sequestration (1.7%), and habitat for biodiversity (6.9%). Using scenario analyses, we identified a two-pronged strategy that would significantly reduce these trade-offs, enhancing regulating services and biodiversity, while simultaneously diversifying and increasing product provision and improving livelihoods. This general approach to analyzing product provision, regulating services, biodiversity, and livelihoods has applicability in rural landscapes across China, South and Southeast Asia, and beyond.

Constructing the bonding interactions between endohedral metallofullerene superatoms by embedded atomic regulation.

We present a possible principle that controls intercluster bonding through embedding different kinds of actinide atoms into the centre of fullerenes, thereby exhibiting different bonding forms. Moreover, these superatoms maintain the robustness of electronic structures.

Predictive role of perioperative neutrophil to lymphocyte ratio in pediatric congenital heart disease associated with pulmonary arterial hypertension.

BACKGROUND: We aimed to explore the relationship between the neutrophil to lymphocyte ratio (NLR) and the early clinical outcomes in children with congenital heart disease (CHD) associated with pulmonary arterial hypertension (PAH) after cardiac surgery. METHODS: A retrospective observational study involving 190 children from January 2013 to August 2019 was conducted. Perioperative clinical and biochemical data were collected. RESULTS: We found that pre-operative NLR was significantly correlated with AST, STB, CR and UA (P < 0.05), while post-operative NLR was significantly correlated with ALT, AST, BUN (P < 0.05). Increased post-operative neutrophil count and NLR as well as decreased lymphocyte count could be observed after cardiac surgery (P < 0.05). Level of pre-operative NLR was significantly correlated with mechanical ventilation time, ICU stay time and total length of stay (P < 0.05), while level of post-operative NLR was only significantly correlated to the first two (P < 0.05). By using ROC curve analysis, relevant areas under the curve for predicting prolonged mechanical ventilation time beyond 24 h, 48 h and 72 h by NLR were statistically significant (P < 0.05). CONCLUSION: For patients with CHD-PAH, NLR was closely related to early post-operative complications and clinical outcomes, and could act as a novel marker to predict the occurrence of prolonged mechanical ventilation.

A novel approach for characterizing variations in serum peptides in rheumatic heart disease.

BACKGROUND & OBJECTIVES: Acute rheumatic fever and rheumatic heart disease (RHD) are important public health problems in developing countries. In this study, peptidomic analyses on RHD patients and healthy individuals were performed to characterize variations in serum peptide levels using label-free quantitation approaches. METHODS: Blood samples were obtained from 160 healthy controls and 160 RHD patients. Of the 448 identified peptides, 272 were analyzed by two label-free mass spectrometry methods, the spectral count and spectral index. RESULTS: There were 38 proteins and 95 peptides with significant (adjusted P<0.001) differences in the abundance of peptides between healthy controls and RHD patients, including multiple peptides derived from histone H2B, villin-like protein, complement C4-B and motile sperm domain containing protein-2. The levels of 10 peptides were upregulated, and 85 peptides were downregulated in patients compared to controls. In addition, in patients, the levels of four proteins were upregulated and 34 were downregulated compared to controls. INTERPRETATION & CONCLUSIONS: This study shows that detection of significant changes in serum peptides reflects the difference between RHD patients and healthy controls. This label-free method may be helpful for clinicians to treat RHD patients during the perioperative period.

Intracellular fate of spherical nucleic acid nanoparticle conjugates.

Spherical nucleic acid (SNA) nanoparticle conjugates are a class of bionanomaterials that are extremely potent in many biomedical applications. Their unique ability to enter multiple mammalian cell types as single-entity agents arises from their novel three-dimensional architecture, which consists of a dense shell of highly oriented oligonucleotides chemically attached typically to a gold nanoparticle core. This architecture allows SNAs to engage certain cell surface receptors to facilitate entry. Here, we report studies aimed at determining the intracellular fate of SNAs and the trafficking events that occur inside C166 mouse endothelial cells after cellular entry. We show that SNAs traffic through the endocytic pathway into late endosomes and reside there for up to 24 h after incubation. Disassembly of oligonucleotides from the nanoparticle core is observed 16 h after cellular entry, most likely due to degradation by enzymes such as DNase II localized in late endosomes. Our observations point to these events being likely independent of core composition and treatment conditions, and they do not seem to be particularly dependent upon oligonucleotide sequence. Significantly and surprisingly, the SNAs do not enter the lysosomes under the conditions studied. To independently track the fate of the particle core and the fluorophore-labeled oligonucleotides that comprise its shell, we synthesized a novel class of quantum dot SNAs to determine that as the SNA structures are broken down over the 24 h time course of the experiment, the oligonucleotide fragments are recycled out of the cell while the nanoparticle core is not. This mechanistic insight points to the importance of designing and synthesizing next-generation SNAs that can bypass the degradation bottleneck imposed by their residency in late endosomes, and it also suggests that such structures might be extremely useful for endosomal signaling pathways by engaging receptors that are localized within the endosome.

Giant vegetation in the right ventricle caused by Staphylococcus aureus and Candida mycoderma.

INTRODUCTION: Infective endocarditis (IE) is considered a multifactorial disease. Providing an early diagnosis and invasive treatment together with effective antibiotic treatment remain critical tasks for the cardiologist and the surgeon. Right ventricular endocarditis is a rare type of endocarditis usually caused by Staphylococcus aureus and Candida mycoderma. CASE PRESENTATION: We present a 25-year-old male patient who presented with persistent malaise, fever, cough, and anorexia after 55 days of antibiotic treatment. Lung computed tomographic scanning excluded severe lung infection. Transthoracic and transesophageal echocardiography revealed a giant vegetation in the right ventricle. Blood culture was positive for S. aureus and C. mycoderma, and antibiotic therapy was immediately applied. Considering the large burden of infected tissue, an early surgical intervention was planned. The cultures of the vegetation specimen were negative. Intraoperative and histological findings confirmed the echocardiographic diagnosis of IE. CONCLUSIONS: Giant vegetations in the right ventricle caused by S. aureus and C. mycoderma are rare. In addition to medical treatment, more attention should be paid to early surgical consultation.

Novel hybrid management for aortic dissection with crevasse in the vicinity of critical branching: report of 53 cases.

Open surgery for aortic dissection with crevasse in the vicinity of critical branching (CVCB-AD) is frequently associated with several complications and a high mortality rate. We report the management of 53 patients with CVCB-AD who underwent a novel hybrid procedure including both open surgery and endovascular stenting. During the follow-up period no paraplegia, stroke, renal failure, or bleeding was observed, and no elective or emergency surgical conversion was required, suggesting that this hybrid procedure is a feasible, safe, and effective strategy for the treatment of CVCB-AD.

Antibacterial Micelles-Loaded Carboxymethyl Chitosan/Oxidized Konjac Glucomannan Composite Hydrogels for Enhanced Wound Repairing.

Antibacterial hydrogels have emerged as a promising approach for effective wound treatment. However, despite extensive research on the fabrication of antibacterial hydrogels, it remains challenging to develop injectable, biocompatible, transparent, and mass-producible hydrogels with antibacterial properties. In this study, we successfully fabricated an antibacterial drug-loaded composite hydrogel, named CC45/OKG40/HS, through a Schiff base reaction between carboxymethyl chitosan (CC) and oxidized konjac glucomannan (OKG), followed by the encapsulation of stevioside-stabilized honokiol (HS) micelles. The CC45/OKG40/HS hydrogel exhibited several favorable properties, including a short gel time (<10 min), high water content (>92%), injectability, good adhesiveness, self-healing ability, and high transparency. In vitro experiments confirmed its excellent antibacterial properties, antioxidant activities, and high biocompatibility (no cytotoxicity, hemolysis ratio <5%). Furthermore, in vivo evaluation demonstrated that the CC45/OKG40/HS0.5 hydrogel accelerated wound healing by relieving inflammatory responses and enhancing re-epithelization. Given its feasibility for mass production, the findings showed that the CC45/OKG40/HS hydrogel has the potential as an advanced antibacterial wound dressing for commercial use.

Therapeutic Potential Evaluation of Silk Sericin Stabilized Fisetin to Ulcerative Colitis.

Ulcerative colitis is a chronic inflammatory bowel disease with a high recurrence rate. Natural phytochemical compounds are increasingly being considered as preventative and supportive treatments for this condition. However, the poor water solubility and stability of many of these compounds limit their effectiveness in vivo. To address this issue, fisetin (FT), a natural phytochemical with poor solubility, is stabilized using silk sericin (SS) to create a composite (SS/FT). The therapeutic potential of the SS/FT on ulcerative colitis is extensively investigated, and the results showed that it effectively alleviated the body weight loss and colon length shortening induced by dextran sulfate sodium. Notably, SS/FT downregulated the immune response, decreased colonic histopathological lesions, and reduced the cGAS/STING signal activation. This suggests that SS/FT may offer a promising therapy for treating ulcerative colitis.

A Hydrogel Dressing Comprised of Silk Fibroin, Ag Nanoparticles, and Reduced Graphene Oxide for NIR Photothermal-Enhanced Antibacterial Efficiency and Skin Regeneration.

Bacterial infection, inflammation, and excessive oxidative stress are the primary factors that contribute to delayed healing of skin wounds. In this study, a multifunctional wound dressing (SF/Ag@rGO hydrogel) is developed to promote the healing of infected skin wounds by combining the inherent antibacterial activity of Ag nanoparticles (NPs) with near-infrared (NIR)-assisted antibacterial therapy. Initially, L-ascorbic acid is used as a reducing agent and PVP-K17 as a stabilizer and dispersant, this facilitates the synthesis of reduced graphene oxide loaded with Ag NPs (Ag@rGO). Ag@rGO is then blended with a silk fibroin (SF) solution to form an instantly gelling SF/Ag@rGO hydrogel that exhibits rapid self-healing, injectability, shape adaptability, NIR responsiveness, antioxidant, high tissue adhesion, and robust mechanical properties. In vitro and in vivo experiments show that the SF/Ag@rGO hydrogel demonstrates strong antioxidant and photothermal antibacterial capabilities, promoting wound healing through angiogenesis, stimulating collagen generation, alleviating inflammation, antioxidant, and promoting cell proliferation, indicating that the SF/Ag@rGO hydrogel dressing is an ideal candidate for clinical treatment of full-thickness bacterial-stained wounds.

Polyvinylpyrrolidone-Polydatin nanoparticles protect against oxaliplatin induced intestinal toxicity in vitro and in vivo.

Oxaliplatin (OXL) is a first-line drug for the treatment of colon cancer, with excellent efficacy. Intestinal toxicity is a common side effect of OXL, with unclear pathogenesis and a lack of effective treatment strategies. Polydatin (PD) has anti-inflammatory and antioxidant activities and is a potential drug for treating intestinal diseases, but its poor water solubility limits its application. In this study, polyvinylpyrrolidone (PVP) was used as a carrier to prepare nanoparticles loaded with PD (PVP-PD), with a particle size of 92.42 nm and exhibiting sustained release properties. In vitro results showed that PVP-PD protected NCM460 cells from OXL induced injury, mitochondrial membrane potential (MMP) disruption, and accumulation of reactive oxygen species (ROS). The in vivo results demonstrated the protective effect of PVP-PD on intestinal toxicity induced by OXL, such as alleviating weight loss and colon length reduction induced by OXL. Both in vivo and in vitro mechanisms indicated that OXL induced DNA damage and activated the cGAS-STING pathway, further inducing the expression of inflammatory factors such as IL-1ß and TNF-α. PVP-PD alleviated the aforementioned changes induced by OXL by inhibiting the DNA damage-cGAS-STING pathway. In summary, our study demonstrated that the DNA damage-cGAS-STING pathway was involved in OXL induced intestinal toxicity, and PVP-PD provided a potential strategy for treating OXL induced intestinal toxicity.

Infectious complications in pediatric patients undergoing CD19+CD22+ chimeric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia.

Chimeric antigen receptor T-cell (CAR-T) therapy is effective in the treatment of relapsed/refractory acute B-lymphoblastic leukemia (R/R B-ALL); however, patients who receive CAR-T therapy are predisposed to infections, with considerable detrimental effects on long-term survival rates and the quality of life of patients. This study retrospectively analyzed infectious complications in 79 pediatric patients with R/R B-ALL treated with CAR-T cells at our institution. Overall, 53 patients developed 88 infections. Nine patients experienced nine infections during lymphodepletion chemotherapy, 35 experienced 41 infections during the early phase (days 0-+ 30 after infusion), and 29 experienced 38 infections during the late phase (day + 31-+ 90 after infusion). Pathogens were identified in 31 infections, including 23 bacteria, seven viruses, and one fungus. Four patients were admitted to the intensive care unit for infection and one died. In a univariate analysis, there were ten factors associated with infection, including tumor load, lymphodepleting chemotherapy, neutrophil deficiency and lymphocyte reduction, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), etc. In a multivariate analysis, CRS ≥ grade 3 was identified as a risk factor for infection (hazard ratio = 2.41, 95% confidence interval: 1.08-5.36, P = 0.031). Therefore, actively reducing the CRS grade may decrease the risk of infection and improve the long-term quality of life of these patients.

The development of local ambient air quality standards: A case study of Hainan Province, China.

The ambient air quality standard (AAQS) is a vital policy instrument for protecting the environment and human health. Hainan Province is at the forefront of China's efforts to protect its ecological environment, with an official goal to achieve world-leading air quality by 2035. However, neither the national AAQS nor the World Health Organization guideline offers sufficient guidance for improving air quality in Hainan because Hainan has well met the former while the latter is excessively stringent. Consequently, the establishment of Hainan's local AAQS becomes imperative. Nonetheless, research regarding the development of local AAQS is scarce, especially in comparatively more polluted countries such as China. The relatively high background values and significant interannual fluctuations in air pollutant concentrations in Hainan present challenges in the development of local AAQS. Our research proposes a world-class local AAQS of Hainan Province by reviewing the AAQS in major countries or regions worldwide, analyzing the influence of different statistical forms, and carefully evaluating the attainability of the standard. In the proposed AAQS, the annual mean concentration limit for PM2.5, the annual 95th percentile of daily maximum 8-h mean (MDA8) concentration limit for O3, and the peak season concentration limit for O3 are set at 10, 120, and 85 µg/m3, respectively. Our study indicates that, with effective control policies, Hainan is projected to achieve compliance with the new standard by 2035. The implementation of the local AAQS is estimated to avoid 1,526 (1,253-1,789) and 259 (132-501) premature deaths attributable to long-term exposure to PM2.5 and O3 in Hainan in 2035, respectively.

Research on the Response Mechanism of Coal Rock Mass under Stress and Pressure.

In this paper, the strength and deformation failure characteristics of bearing coal rock mass are related to the confining pressure, and the SAS-2000 experimental system is used to carry out uniaxial and 3, 6, and 9 MPa triaxial tests on coal rock to assess the strength and deformation failure characteristics of coal rock under different confining pressure conditions. The results show that the stress-strain curve of coal rock undergoes four evolutionary stages after fracture: compaction, elasticity, plasticity, and rupture. With confining pressure, the peak strength of coal rock increases, and the elastic modulus increases nonlinearly. The coal sample changes more with confining pressure, and the elastic modulus is generally smaller than that of fine sandstone. The stage of evolution under confining pressure constitutes the failure process of coal rock, with the stress of different evolution stages causing various degrees of damage to coal rock. In the initial compaction stage, the unique pore structure of the coal sample makes the confining pressure effect more apparent; the confining pressure makes the bearing capacity of the coal rock plastic stage stronger, the residual strength of the coal sample has a linear relationship with the confining pressure, and the residual strength of the fine sandstone has a nonlinear relationship with the confining pressure. Changing the confining pressure state will cause the two kinds of coal rock samples to change from brittle failure to plastic failure. Different coal rocks under uniaxial compression experience more brittle failure, and the overall degree of crushing is higher. The coal sample in the triaxial state experiences predominantly ductile fracture. The whole is relatively complete after failure as a shear failure occurs. The fine sandstone specimen experiences brittle failure. The degree of failure is low, and the confining pressure's effect on the coal sample is obvious.