AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity.

Nutrient sensing and damage sensing are two fundamental processes in living organisms. While hyperglycemia is frequently linked to diabetes-related vulnerability to microbial infection, how body glucose levels affect innate immune responses to microbial invasion is not fully understood. Here, we surprisingly found that viral infection led to a rapid and dramatic decrease in blood glucose levels in rodents, leading to robust AMPK activation. AMPK, once activated, directly phosphorylates TBK1 at S511, which triggers IRF3 recruitment and the assembly of MAVS or STING signalosomes. Consistently, ablation or inhibition of AMPK, knockin of TBK1-S511A, or increased glucose levels compromised nucleic acid sensing, while boosting AMPK-TBK1 cascade by AICAR or TBK1-S511E knockin improves antiviral immunity substantially in various animal models. Thus, we identify TBK1 as an AMPK substrate, reveal the molecular mechanism coupling a dual sensing of glucose and nuclei acids, and report its physiological necessity in antiviral defense.

TTD: Therapeutic Target Database describing target druggability information.

Target discovery is one of the essential steps in modern drug development, and the identification of promising targets is fundamental for developing first-in-class drug. A variety of methods have emerged for target assessment based on druggability analysis, which refers to the likelihood of a target being effectively modulated by drug-like agents. In the therapeutic target database (TTD), nine categories of established druggability characteristics were thus collected for 426 successful, 1014 clinical trial, 212 preclinical/patented, and 1479 literature-reported targets via systematic review. These characteristic categories were classified into three distinct perspectives: molecular interaction/regulation, human system profile and cell-based expression variation. With the rapid progression of technology and concerted effort in drug discovery, TTD and other databases were highly expected to facilitate the explorations of druggability characteristics for the discovery and validation of innovative drug target. TTD is now freely accessible at: https://idrblab.org/ttd/.

TheMarker: a comprehensive database of therapeutic biomarkers.

Distinct from the traditional diagnostic/prognostic biomarker (adopted as the indicator of disease state/process), the therapeutic biomarker (ThMAR) has emerged to be very crucial in the clinical development and clinical practice of all therapies. There are five types of ThMAR that have been found to play indispensable roles in various stages of drug discovery, such as: Pharmacodynamic Biomarker essential for guaranteeing the pharmacological effects of a therapy, Safety Biomarker critical for assessing the extent or likelihood of therapy-induced toxicity, Monitoring Biomarker indispensable for guiding clinical management by serially measuring patients' status, Predictive Biomarker crucial for maximizing the clinical outcome of a therapy for specific individuals, and Surrogate Endpoint fundamental for accelerating the approval of a therapy. However, these data of ThMARs has not been comprehensively described by any of the existing databases. Herein, a database, named 'TheMarker', was therefore constructed to (a) systematically offer all five types of ThMAR used at different stages of drug development, (b) comprehensively describe ThMAR information for the largest number of drugs among available databases, (c) extensively cover the widest disease classes by not just focusing on anticancer therapies. These data in TheMarker are expected to have great implication and significant impact on drug discovery and clinical practice, and it is freely accessible without any login requirement at: https://idrblab.org/themarker.

A task-specific encoding algorithm for RNAs and RNA-associated interactions based on convolutional autoencoder.

RNAs play essential roles in diverse physiological and pathological processes by interacting with other molecules (RNA/protein/compound), and various computational methods are available for identifying these interactions. However, the encoding features provided by existing methods are limited and the existing tools does not offer an effective way to integrate the interacting partners. In this study, a task-specific encoding algorithm for RNAs and RNA-associated interactions was therefore developed. This new algorithm was unique in (a) realizing comprehensive RNA feature encoding by introducing a great many of novel features and (b) enabling task-specific integration of interacting partners using convolutional autoencoder-directed feature embedding. Compared with existing methods/tools, this novel algorithm demonstrated superior performances in diverse benchmark testing studies. This algorithm together with its source code could be readily accessed by all user at: https://idrblab.org/corain/ and https://github.com/idrblab/corain/.

Genome-wide functional integration identified MAZ-controlled RPS14 dysregulation in hepatocellular carcinoma.

Chronic infection with Hepatitis B virus (HBV) significantly increases the risk of hepatocellular carcinoma (HCC), particularly in Eastern Asia. However, only a subset of individuals with chronic HBV infection develop HCC, suggesting the role for genetic factors in HCC etiology. Despite genome-wide association studies (GWASs) identifying multiple single nucleotide polymorphisms (SNPs) associated with HBV-related HCC susceptibility, the underlying mechanisms and causal genetic polymorphisms remain largely unclear. To address this, we developed The Updated Integrative Functional Genomics Approach (TUIFGA), an methodology that combines data from transcription factor (TF) cistromics, ATAC-seq, DNAase-seq, and the 1000 Genomes Project to identify cancer susceptibility SNPs within TF-binding sites across human genome. Using TUIFGA, we discovered SNP rs13170300 which located in the TF MAZ binding motif of RPS14. The RPS14 rs13170300 was significantly associated with HCC risk in two case-control sets, with the T allele as the protective allele (Shandong discovery set: TT OR = 0.60, 95% CI = 0.49-0.74, P = 1.0 × 10-6; CT OR = 0.69, 95% CI = 0.55-0.86, P = 0.001; Jiangsu validation set: TT OR = 0.70, 95% CI = 0.56-0.87, P = 0.001; CT OR = 0.65, 95% CI = 0.53-0.82, P = 1.6 × 10-4). SNP rs13170300 affected MAZ binding in the RPS14 promoter, resulting in allele-specific changes in gene expression. RPS14 functions as a novel oncogene in HCC, specifically via activating the AKT signaling. Our findings present important insights into the functional genetics underlying HBV-related HCC development and may contribute to personalized approaches for cancer prevention and novel therapeutics.

Targeting proteostasis of the HEV replicase to combat infection in preclinical models.

BACKGROUND & AIMS: Appropriate treatment options are lacking for hepatitis E virus (HEV)-infected pregnant women and immunocompromised individuals. Thus, we aimed to identify efficient anti-HEV drugs through high-throughput screening, validate them in vitro and in vivo (in a preclinical animal study), and elucidate their underlying antiviral mechanism of action. METHODS: Using appropriate cellular and rodent HEV infection models, we studied a critical pathway for host-HEV interactions and performed a preclinical study of the corresponding antivirals, which target proteostasis of the HEV replicase. RESULTS: We found 17 inhibitors that target HEV-HSP90 interactions by unbiased compound library screening on human hepatocytes harboring an HEV replicon. Inhibitors of HSP90 (iHSP90) markedly suppressed HEV replication with efficacy exceeding that of conventional antivirals (IFNα and ribavirin) in vitro. Mechanistically, iHSP90 treatment released the viral replicase ORF1 protein from the ORF1-HSP90 complex and triggered rapid ubiquitin/proteasome-mediated degradation of ORF1, resulting in abrogated HEV replication. Furthermore, a preclinical trial in a Mongolian gerbil HEV infection model showed this novel anti-HEV strategy to be safe, efficient, and able to prevent HEV-induced liver damage. CONCLUSIONS: In this study, we uncover a proteostatic pathway that is critical for host-HEV interactions and we provide a foundation from which to translate this new understanding of the HEV life cycle into clinically promising antivirals. IMPACT AND IMPLICATIONS: Appropriate treatment options for hepatitis E virus (HEV)-infected pregnant women and immunocompromised patients are lacking; hence, there is an urgent need for safe and effective HEV-specific therapies. This study identified new antivirals (inhibitors of HSP90) that significantly limit HEV infection by targeting the viral replicase for degradation. Moreover, these anti-HEV drugs were validated in an HEV rodent model and were found to be safe and efficient for prevention of HEV-induced liver injury in preclinical experiments. Our findings substantially promote the understanding of HEV pathobiology and pave the way for antiviral development.

Drinking Water in Rural China: Water Sources, Treatment, and Boiling Energy.

Access to safe drinking water is a major public concern in China. A national survey of 57 029 households was conducted to fill major knowledge gaps on drinking water sources, end-of-use treatment methods, and energy used to boil water. Herein, we show that surface water and well water were frequently used by >147 million rural residents living in low-income inland and mountainous areas. Driven by socioeconomic development and government intervention, the level of access to tap water in rural China increased to 70% by 2017. Nevertheless, the rate was considerably lower than that in cities and unevenly distributed across the country. Approximately 90% of drinking water was boiled, an increase from 85% a decade ago. The contribution of electricity, mainly electric kettles, to the boiling of water was 69%. Similar to cooking, living conditions and heating requirements are the main influencing indicators of energy used to boil water. In addition to socioeconomic development, government intervention is a key factor driving the transition to safe water sources, universal access to tap water, and clean energy. Further improvement in drinking water safety in poor and remote rural areas remains challenging, and more intervention and more investment are needed.

Jionoside A1 alleviates ischemic stroke ischemia/reperfusion injury by promoting Nix-mediated mitophagy.

In ischemia-reperfusion injury in ischemic stroke, mitophagy, which can remove damaged mitochondria, reduce cytotoxic damage, and enhance neurological recovery, is crucial. Jionoside A1 is a substance found in the traditional Chinese herb Rehmannia glutinosa, which may have neuroprotective effects. The fundamental objective of this work was to find out Jionoside A1's contribution to ischemia/reperfusion injury in ischemic stroke. The oxygen-glucose deprivation/reperfusion (OGD-Rep) model and the right transient middle cerebral artery occlusion (tMCAO) model were established. Jionoside A1 was used for treatment. We utilized a tiny interfering RNA (siRNA) to lower Nix expression. The results suggest that Jionoside A1 may reduce ischemic stroke. By lowering the consequences of ischemia/reperfusion injury, Rehmannia glutinosa can be utilized to treat ischemic stroke. These discoveries provide fresh experimental information for the investigation of ischemic stroke ischemia/reperfusion injury and provide some theoretical justification for their application.

A prediction model for moderate to severe cancer-related fatigue in colorectal cancer after chemotherapy: a prospective case‒control study.

AIMS: The study aims to develop a model to predict the risk of moderate to severe cancer-related fatigue (CRF) in colorectal cancer patients after chemotherapy. METHODS: The study population was colorectal cancer patients who received chemotherapy from September 2021 to June 2022 in a grade 3 and first-class hospital. Demographic, clinical, physiological, psychological, and socioeconomic factors were collected 1 to 2 days before the start of chemotherapy. Patients were followed up for 1 to 2 days after the end of chemotherapy to assess fatigue using the Piper Fatigue Scale. A random sampling method was used to select 181 patients with moderate to severe CRF as the case group. The risk set sampling method was used to select 181 patients with mild or no CRF as the control group. Logistic regression, back-propagation artificial neural network (BP-ANN), and decision tree models were constructed and compared. RESULTS: A total of 362 patients consisting of 241 derivation samples and 121 validation samples were enrolled. Comparing the three models, the prediction effect of BP-ANN was the best, with a receiver operating characteristic (ROC) curve of 0.83. Internal and external verification indicated that the accuracy of prediction was 70.4% and 80.8%, respectively. Significant predictors identified were surgery, complications, hypokalaemia, albumin, neutrophil percentage, pain (VAS score), Activities of Daily Living (ADL) score, sleep quality (PSQI score), anxiety (HAD-A score), depression (HAD-D score), and nutrition (PG-SGA score). CONCLUSIONS: BP-ANN was the best model, offering theoretical guidance for clinicians to formulate a tool to identify patients at high risk of moderate to severe CRF.

A systematic review and meta-analysis comparing outcomes following total knee arthroplasty for rheumatoid arthritis versus for osteoarthritis.

PURPOSE: Total knee arthroplasty (TKA) in patients with osteoarthritis (OA) are considered to be a successful procedure, but with little being known about outcomes in patients with rheumatoid arthritis (RA). The aim of this study was to compare the outcomes of TKA in patients with RA versus OA. METHODS: Data were obtained from PubMed, Cochrane Library, EBSCO and Scopus for all available studies comparing the outcomes of THA in RA and OA patients (From January 1, 2000 to October 15, 2022). Outcomes of interest included infection, revision, venous thromboembolism (VTE), mortality, periprosthetic fractures, prosthetic loosening, length of stay, and satisfaction. Two reviewers independently assessed each study for quality and extracted data. The quality of the studies was scored using the Newcastle-Ottawa scale (NOS). RESULTS: Twenty-four articles with a total 8,033,554 patients were included in this review. The results found strong evidence for increased risk of overall infection (OR = 1.61, 95% CI, 1.24-2.07; P = 0.0003), deep infection (OR = 2.06, 95% CI, 1.37-3.09; P = 0.0005), VTE (OR = 0.76, 95% CI, 0.61-0.93; P = 0.008), pulmonary embolism (PE) (OR = 0.84, 95% CI, 0.78-0.90; P<0.00001), periprosthetic fractures (OR = 1.87, 95% CI, 1.60-2.17; P<0.00001); and reasonable evidence for increased risk of deep venous thrombosis (DVT) (OR = 0.74, 95% CI, 0.54-0.99; P = 0.05), and length of stay (OR = 0.07, 95% CI, 0.01-0.14; P = 0.03) after TKA in patients with RA versus OA. There were no significant differences in superficial site infection (OR = 0.84,95% CI, 0.47-1.52; P = 0.57), revision (OR = 1.33,95% CI, 0.79-2.23; P = 0.28), mortality (OR = 1.16,95% CI, 0.87-1.55; P = 0.32), and prosthetic loosening (OR = 1.75, 95% CI, 0.56-5.48; P = 0.34) between the groups. CONCLUSION: Our study demonstrated that patients with RA have a higher risk of postoperative infection, VTE, periprosthetic fracture, and lengths of stay, but did not increase revision rate, prosthetic loosening and mortality compared to patients with OA following TKA. In conclusion, despite RA increased incidence of postoperative complications, TKA should continue to be presented as an effective surgical procedure for patients whose conditions are intractable to conservative and medical management of RA.

Regulation of M1/M2 Polarization in LPS-Stimulated Macrophages by 1,25(OH)2D3.

Objective: This study aims to investigate the impact of 1,25(OH)2D3 on the polarization of LPS-stimulated macrophages and the underlying regulatory mechanisms. Methods: Primary macrophages were isolated and identified using immunofluorescence assays to detect macrophage biomarker expression levels. RT-PCR was employed to measure the expression of Arginase 1 (Arg-1), Interleukin-10 (IL-10), Inducible isoform of nitric oxide synthase (iNOS), and Tumor necrosis factor-α (TNF-α) in macrophages treated with various strategies. Western blotting assessed the protein expression levels of AKT1, p-AKT1, NF-κB p65, p-NF-κB p65, STAT3, and p-STAT3 in LPS-stimulated macrophages exposed to different concentrations of 1,25(OH)2D3. Results: As the LPS concentration increased from 0 to 0.5 mg/L, Arg-1, IL-10, iNOS, and TNF-α expression levels significantly increased. However, at LPS concentrations ranging from 1 mg/L to 10 mg/L, the expression of Arg-1, IL-10, iNOS, and TNF-α displayed a trend from increase to decline. The highest M2 polarization (Arg-1 and IL-10) was observed in macrophages stimulated with 0.5 mg/L LPS among the lower concentrations, while the highest M1 polarization (iNOS and TNF-α) was observed in macrophages stimulated with 5 mg/L LPS among the higher concentrations. Subsequent experiments utilized 0.5 mg/L and 5 mg/L LPS as incubation concentrations. Under LPS stimulation, iNOS was significantly upregulated, surpassing the expression level of IL-10, a marker of M2 macrophages. The introduction of 1,25(OH)2D3 facilitated M2 polarization, with 50 nM as the incubation concentration of 1,25(OH)2D3. Furthermore, 1,25(OH)2D3 reversed the elevated expression of p-AKT1, p-NF-κB p65, and p-STAT3 in macrophages stimulated with 5 mg/L LPS. Conclusions: 1,25(OH)2D3 effectively regulates the M1/M2 polarization in LPS-stimulated macrophages.

Clinical effects of interspace between the popliteal artery and capsule of the posterior knee block with multimodal analgesia for total knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: Combination of regional anaesthesia technique that is most effective in analgesia and postoperative functional outcome with the fewest complications needs investigation. Interspace between the popliteal artery and the capsule of the posterior knee block (IPACK) has been introduced clinically. We evaluated the efficacy of IPACK in combination with other nerve blocks after total knee arthroplasty. METHODS: Data were obtained from PubMed, Cochrane Library, Web of Science, and Sciencedirect. Studies that compared outcomes using IPACK combined with other regional nerve blocks after total knee arthroplasty with other analgesic modalities and those which used pain scores or opioid consumption as primary or secondary outcomes were included. RESULTS: Seventeen articles (20 trials, 1652 patients) were included. IPACK supplementation significantly reduced rest pain scores after total knee arthroplasty at postoperative hours 8-12(95%CI - 0.85 [- 1.36, - 0.34], I2 = 94%, p = 0.001), postoperative day 1 (95% CI - 0.49 [- 0.85, - 0.14], I2 = 87%, p = 0.006), and postoperative day 2 (95% CI - 0.28 [- 0.51, -0.05], I2 = 72%, p = 0.02); there was no significant difference at postoperative day 3 or discharge (95% CI - 0.14 [- 0.33, 0.05], I2 = 0%, p = 0.14). Combination treatment resulted in reduced dynamic pain scores at postoperative hours 8-12 (95%CI - 0.52 [- 0.92, - 0.12], I2 = 86%, p = 0.01) and postoperative day 1(95% CI - 0.49 [- 0.87, - 0.11], I2 = 88%, p = 0.01). There was no difference between postoperative day 2(95% CI - 0.29 [- 0.63, 0.05], I2 = 80%, p = 0.09), postoperative day 3 or discharge (95% CI - 0.45 [- 0.92, 0.02], I2 = 83%, p = 0.06). In addition, it strongly reduced postoperative opioid consumption within 24 H (95% CI - 0.76 [- 1.13, - 0.39], I2 = 85%, p < 0.00001), 24-48 H (95% CI - 0.43 [- 0.85, - 0.01], I2 = 83%, p = 0.04), and total opioid use (95% CI - 0.64 [- 1.07, - 0.22], I2 = 86%, p = 0.003). Although IPACK supplementation improved timed up and go test and walking distance at postoperative day 2, there was no statistically significant difference at other time periods or obvious improvement in knee range of motion and quadriceps strength. IPACK block supplementation could shorten the length of stay (LOS) (95% CI - 0.40 [- 0.64, - 0.15], I2 = 70%, p = 0.001) and improve patient satisfaction (95% CI 0.43 [0.01, 0.84], I2 = 87%, p = 0.04). CONCLUSION: Based on these results, IPACK supplementation, in addition to standard postoperative analgesia, can be used effectively and safely to relieve early postoperative pain after total knee arthroplasty.

Haloterrigena gelatinilytica sp. nov., a new extremely halophilic archaeon isolated from salt-lake.

Two extremely halophilic strains, designated SYSU A558-1T and SYSU A121-1, were isolated from a saline sediment sample collected from Aiding salt-lake, China. Cells of strains SYSU A558-1T and SYSU A121-1 were Gram-stain-negative, coccoid, and non-motile. The strains were aerobic and grew at NaCl concentration of 10-30% (optimum, 20-22%), at 20-55 °C (optimum, 37-42 °C) and at pH 6.5-8.5 (optimum, 7.0-8.0). Cells lysed in distilled water. The polar lipids were phosphatidyl choline, phosphatidylglycerol phosphate methyl ester, disulfated diglycosyl diether-1 and unidentified glycolipid. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the two strains SYSU A558-1T and SYSU A121-1 were closely related to the membranes of the genus Haloterrigena. Phylogenetic and phylogenomic trees of strains SYSU A558-1T and SYSU A121-1 demonstrated a robust clade with Haloterrigena turkmenica, Haloterrigena salifodinae and Haloterrigena salina. The genomic DNA G + C content of strains SYSU A558-1T and SYSU A121-1 were 65.8 and 65.0%, respectively. Phenotypic, phylogenetic, chemotaxonomic and genome analysis suggested that the two strains SYSU A558-1T and SYSU A121-1 represent a novel species of the genus Haloterrigena, for which the name Haloterrigena gelatinilytica sp. nov. is proposed. The type strain is SYSU A558-1T (= KCTC 4259T = CGMCC 1.15953T).

Risk factors for cancer-related fatigue in patients with colorectal cancer: a systematic review and meta-analysis.

PURPOSE: Cancer-related fatigue seriously affects the quality of life of cancer patients, yet few systematic reviews have evaluated the risk factors for cancer-related fatigue in patients with colorectal cancer. We therefore conducted a meta-analysis to assess the risk factors of cancer-related fatigue in patients with colorectal cancer. METHODS: Literature databases, including PubMed, Ovid, Embase, the Cochrane Central Register of Controlled Trials, the Web of Science, the China National Knowledge Infrastructure, Wanfang, and VIP, were searched from their establishment to September 2021 to identify suitable studies. The quality of included studies was assessed using different tools and evaluated independently by two investigators. Review Manager version 5.4 (Cochrane Collaboration, London, UK) was used for statistical analysis, and sensitivity analysis was conducted. RESULTS: In total, 2642 articles were screened, and data from 25 studies involving 8733 subjects were included in this meta-analysis. After controlling for confounding variables, the following risk factors were associated with cancer-related fatigue: younger age, female sex, low physical activity level, a clinical stage of III or IV, surgery, chemotherapy, insomnia, pain, anxiety, and depression. CONCLUSION: Younger age, female sex, low physical activity level, a clinical stage of III or IV, chemotherapy, pain, insomnia, anxiety, and depression were identified as risk factors for cancer-related fatigue. Future research should focus on how multidisciplinary teams adopt targeted measures according to these risk factors to better reduce the incidence of cancer-related fatigue.

Improved YOLOX detection algorithm for contraband in X-ray images.

It is important to perform contraband inspections on items before they are taken into public places in order to ensure the safety of people and property. At present, the mainstream method of judging contraband is that security inspectors observe the X-ray image of objects and judge whether they belong to contraband. Unfortunately, contraband is often hidden under other normal objects. In a high-intensity working environment, security inspectors are very prone to missed detection and wrong detection. To this end, a detection framework based on computer vision technology is proposed, which is trained and improved on the basis of the current state-of-the-art YOLOX object detection network, and adopts strategies such as feature fusion, adding a double attention mechanism and classifying regression loss. Compared with the benchmark YOLOX-S model, the proposed method achieves a higher average accuracy, with an improvement of 5.0% on the public safety SIXray dataset, opening the way to large-scale automatic detection of contraband in public places.

Updated Global Black Carbon Emissions from 1960 to 2017: Improvements, Trends, and Drivers.

Accurate estimation of black carbon (BC) emissions is essential for assessing the health and climate impact of this pollutant. Past emission inventories were associated with high uncertainty due to data limitations, and recent information has provided a unique updating opportunity. Moreover, understanding the drivers that cause temporal emission changes is of research value. Here, we update the global BC emission estimates using new data on the activities and emission factors (EFs). The new inventory covers 73 detailed sources at 0.1° × 0.1° spatial resolution and monthly temporal resolution from 1960 to 2017. The estimated annual emissions were 32% higher than the average of several previous inventories, which was primarily due to field-measured EFs for residential stoves and differentiated EFs for motor vehicles. In addition, the updated emissions show an inverse U-shaped temporal trend, which was mainly driven by the interaction between the positive effects of population growth, per capita energy consumption, and vehicle fleet and the negative effects of residential energy switching, stove upgrading, phasing out of beehive coke ovens, and reduced EFs for vehicles and industrial processes. Urbanization caused a significant increase in urban emissions accompanied by a more significant decline in rural emissions.

Direct and Inverse Reduced-Form Models for Reciprocal Calculation of BC Emissions and Atmospheric Concentrations.

Atmospheric black carbon (BC) concentrations are governed by both emissions and meteorological conditions. Distinguishing these effects enables quantification of the effectiveness of emission mitigation actions by excluding meteorological effects. Here, we develop reduced-form models in both direct (RFDMs) and inverse (RFIMs) modes to estimate ambient BC concentrations. The models were developed based on outputs from multiyear simulations under three conditional scenarios with realistic or fixed emissions and meteorological conditions. We established a set of probabilistic functions (PFs) to quantify the meteorological influences. A significant two-way linear relationship between multiyear annual emissions and mean ambient BC concentrations was revealed at the grid cell scale. The correlation between them was more significant at grid cells with high emission densities. The concentrations and emissions at a given grid cell are also significantly correlated with emissions and concentrations of the surrounding areas, respectively, although to a lesser extent. These dependences are anisotropic depending on the prevailing winds and source regions. The meteorologically induced variation at the monthly scale was significantly higher than that at the annual scale. Of the major meteorological parameters, wind vectors, temperature, and relative humidity were found to most significantly affect variation in ambient BC concentrations.

Coal Is Dirty, but Where It Is Burned Especially Matters.

Coal abatement actions for pollution reduction often target total coal consumption. The health impacts of coal uses, however, vary extensively among sectors. Here, we modeled the sectorial contributions of coal uses to emissions, outdoor and indoor PM2.5 (particulate matter with an aerodynamic diameter of less than 2.5 mm) concentrations, exposures, and health outcomes in China from 1970 to 2014. We show that in 2014, residential coal accounted for 2.9% of total energy use but 34% of premature deaths associated with PM2.5 exposure, showing that effects were magnified substantially along the causal path. The number of premature deaths attributed to unit coal consumption in the residential sector was 40 times higher than that in the power and industrial sectors. Emissions of primary PM2.5 were more important than secondary aerosol precursors in terms of health consequences, and indoor exposure accounted for 97% and 91% of total premature deaths attributable to PM2.5 from coal combustion in 1974 and 2014, respectively. Our assessment raises a critical challenge in the switching of residential coal uses to effectively mitigate PM2.5 exposure in the Chinese population.

[Evidence mapping of clinical research on 28 Chinese patent medicines for tension-type headache].

In this study, the evidence mapping methodology was used to systematically retrieve and sort out the clinical research evidence of Chinese patent medicines in the treatment of tension-type headache(TTH), and to understand the distribution of evidence in this field and the basis and quality of evidence. Chinese and English articles on the 28 Chinese patent medicines for TTH, which were recorded in National Essential Medicines List(2018), Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance(2020), and Chinese Pharmacopoeia(2020), were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, China Biology Medicine disc(CBMdisc), PubMed, EMbase, and Cochrane Library from the establishment to June 2021, followed by descriptive analysis. Then, tables and bubble charts were plotted to analyze the distribution characteristics of evidence. A total of 129 eligible articles were yielded: 126 randomized/non-randomized controlled trials, and 3 systematic reviews. The functions, indications, and composition of the 28 medicines, as well as the proportion of related articles, publication trends, intervention measures, and outcome indicators were compared and analyzed. The results showed that the 28 Chinese patent medicines, composed of 128 Chinese medicinals, can be classified into six categories in terms of function: reinforcing healthy Qi, tranquilizing mind, dispelling stasis, regulating Qi, treating wind, and resuscitating. There are ongoing efforts to study the treatment of TTH with Chinese patent medicine in China, despite of little evidence. The clinical positioning of Chinese patent medicine for TTH is not clear, and clinical research fails to highlight the advantages of Chinese medicine. In addition, the outcome indicators have not been standardized and unified, and there is a lack of evidence on the long-term efficacy of Chinese patent medicine for TTH. This study is the first exploratory application of evidence maps to compare the characteristics and clinical research progress of 28 Chinese patent medicines for TTH, which can provide a reference for research on the optimization of Chinese medicine strategies for TTH.

Differentiated-Rate Clean Heating Strategy with Superior Environmental and Health Benefits in Northern China.

Residential heating using solid fuels contributes significantly to air pollution and has subsequent health impacts in China. To mitigate emissions, a clean heating campaign (CHC-1) covering 28 municipalities has been implemented. Although only a single penetration rate was initially planned by CHC-1 for all municipalities, outcomes in the different municipalities varied considerably. Recently, a second phase (CHC-2) has been launched for the remaining 128 municipalities in northern China with once again a fixed penetration rate set. Here, we quantified factors that affected the penetration rates of CHC-1, developed an intervention scheme with differentiated targets for CHC-2, and compared the environmental and health benefits of the fixed- and differentiated-rate strategies. We found that the penetration rates of CHC-1 depended on per capita income, terrain slope, and population density and that such relationships could be quantified using a piecewise regression model. This model was applied to develop a differentiated-rate strategy for CHC-2. It clearly evidenced that a differentiated scheme would be more environmentally beneficial. Although the same number of rural households can achieve clean heating under both intervention scenarios, the proposed differentiated strategy can prevent 30 000 (23 000-34 000) premature deaths associated with residential heating annually compared to the 26 000 (21 000-31 000) premature deaths prevented under the fixed-rate scheme. Differences among gender and age groups and the effects of urbanization and aging are also discussed.