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Coal is a major resource in China both for chemicals production and power generation, but its impact on the environment demands attention. Solvent pretreatment is an effective method to realize cleaner utilization of coal. Shendong sub-bituminous coal was treated with three different deep eutectic solvents (DESs) – choline chloride (ChCl)-urea, ChCl-glycerol, and ChCl- ethylene glycol – at temperature as low as 120°C. Proximate/ultimate analyses, scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy were used to examine the physicochemical changes that occurred in coal after DESs treatment. Results showed that DES treatment led to coal fragmentation and decreased average particle size. Compared with raw coal (33.1%), DES-treated coal showed greater mass loss (35.2 − 37.7%), showing that the amount of low molecular mass species increased after treatment. This was confirmed by the observation that DES-treated coal had more volatile components and less minerals and functional groups that contained oxygen (especially C−O). The content of elemental sulfur also decreased from 0.26% to 0.10 − 0.15% after DES treatment, along with a reduction in aliphatic chain length and aromatic substitution degree, which were from 10.73 to 9.33−10.08 and 16.70% to 10.73−15.36%, respectively. The macromolecular structure of the coal was destroyed as a result of DES’s interactions with the weak covalent bonds and hydrogen bonds in the coal. These results suggest that DES has the potential to be used as a pretreatment solvent for coal conversion.

We describe here a method to generate both benzoyl fluorides and benzoic acids using 2,5-cyclohexadienones prepared from phenols.

Sometimes, people can be exposed to moderate or high doses of radiation accidentally or through the environment. Radiation can cause great harm to several systems within organisms, especially the hematopoietic system. Several types of drugs protect the hematopoietic system against radiation damage in different ways. They can be classified as "synthetic drugs" and "natural compounds." Their cellular mechanisms to protect organisms from radiation damage include free radical-scavenging, anti-oxidation, reducing genotoxicity and apoptosis, and alleviating suppression of the bone marrow. These topics have been reviewed to provide new ideas for the development and research of drugs alleviating radiation-induced damage to the hematopoietic system.

Electrospun fibers containing levocetirizine, a BCS III drug, were prepared from three water-soluble polymers, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA). Fiber-spinning technology was optimized for each polymer separately. The polymers contained 10 wt% of the active component. An amorphous drug was homogeneously distributed within the fibers. The solubility of the drug in the polymers used was limited, with a maximum of 2.0 wt%, but it was very large in most of the solvents used for fiber spinning and in the dissolution media. The thickness of the fibers was uniform and the presence of the drug basically did not influence it at all. The fiber diameters were in the same range, although somewhat thinner fibers could be prepared from PVA than from the other two polymers. The results showed that the drug was amorphous in the fibers. Most of the drug was located within the fibers, probably as a separate phase; the encapsulation efficiency proved to be 80–90%. The kinetics of the drug release were evaluated quantitatively by the Noyes–Whitney model. The released drug was approximately the same for all the polymers under all conditions (pH), and it changed somewhere between 80 and 100%. The release rate depended both on the type of polymer and pH and varied between 0.1 and 0.9 min−1. Consequently, the selection of the carrier polymer allowed for the adjustment of the release rate according to the requirements, thus justifying the use of electrospun fibers as carrier materials for levocetirizine.

China experienced a major nationwide wave of SARS-CoV-2 infections in December 2022, immediately after lifting strict interventions, despite the majority of the population having already received inactivated COVID-19 vaccines. Due to the rapid waning of protection and the emergence of Omicron XBB.1.5, the risk of another COVID-19 wave remains high. It is still unclear whether the health care system will be able to manage the demand during this potential XBB.1.5 wave and if the number of associated deaths can be reduced to a level comparable to that of seasonal influenza. Thus, we developed a mathematical model of XBB.1.5 transmission using Shanghai as a case study. We found that a potential XBB.1.5 wave is less likely to overwhelm the health care system and would result in a death toll comparable to that of seasonal influenza, albeit still larger, especially among elderly individuals. Our analyses show that a combination of vaccines and antiviral drugs can effectively mitigate an XBB.1.5 epidemic, with a projected number of deaths of 2.08 per 10,000 individuals.This figure corresponds to a 70–80% decrease compared to the previous Omicron wave and is comparable to the level of seasonal influenza. The peak prevalence of hospital admissions and ICU admissions are projected at 28.89 and 2.28 per 10,000 individuals, respectively, suggesting the need for a moderate increase in the capacity of the health care system. Our findings emphasize the importance of improving vaccination coverage, particularly among the older population, and the use of antiviral treatments.

Supplemental Figures 1-4 with figure legends and Supplemental Table

PDF file - 14.9MB, Loss of P53 expedited the kinetics of MEF cell reprogramming

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PDF file - 88K, Different from P53, P63 and P73 were not directly involved in iPSC generation.

PDF file - 415K, Normal stem cells can be cultured under temperatures ranged from 32C to 39C and normal iPSC can be formed from MEF cells under these temperatures.

Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection., Currently, there are no treatments or vaccines against Epstein-Barr virus (EBV) infection. Here, Zhu et al. isolate gH/gL-specific antibodies from infected donors and identify 1D8, that substantially reduces infection levels in both, B- and epithelial cells, and reduces tumor burdens in EBV-challanged humanized mice due to interferance with the gH/gL-mediated membrane fusion and binding.

Supplementary Material 1

Additional file 1. Supplementary Information.

In an attempt to improve the solubility of valsartan, a BCS II drug, fibers containing the drug were prepared from three water-soluble polymers, hydroxypropyl-methyl-cellulose (HPMC), polyvinyl-pyrrolidone (PVP), and polyvinyl-alcohol (PVA). Fiber spinning technology was optimized for each polymer separately. The polymers contained 20 wt% of the active component. The drug was homogenously distributed within the fibers in the amorphous form. The presence of the drug interfered with the spinning process only slightly, the diameters of the fibers were in the same range as without the drug for the HPMC and the PVA fibers, while it doubled in PVP. The incorporation of the drug into the fibers increased its solubility in all cases compared to that of the neat drug. The solubility of the drug itself depends very much on pH and this sensitivity remained the same in the HPMC and PVP fibers; the release of the drug is dominated by the dissolution behavior of valsartan itself. On the other hand, solubility and the rate of release were practically independent of pH in the PVA fibers. The different behavior is explained by the rate of the dissolution of the respective polymer, which is larger for HPMC and PVP, and smaller for PVA than the dissolution rate of the drug. The larger extent of release compared to neat valsartan can be explained by the lack of crystallinity of the drug, its better dispersion, and the larger surface area of the fibers. Considering all facts, the preparation of electrospun devices from valsartan and water-soluble polymers is beneficial, and the use of PVA is more advantageous than that of the other two polymers.

Background The CELF gene family is a set of highly conserved genes that encode a family of RNA-binding proteins in human tissues and participate in posttranscriptional modifications. The CELF gene family has been reported to be associated with a variety of cancers, including lung cancer, liver cancer and colorectal cancer. However, the expression, function and clinical relevance of CELF family members in glioma remain uncertain because of the lack of relevant studies. Materials & methods Bioinformatics analysis was used to determine the prognostic value and immune infiltration associations of CELF gene family members in glioma. Transcription and survival data related to CELF gene family members in glioma patients were obtained from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and cBioPortal databases. Results The results revealed that compared to that in normal tissues, the expression of CELF2-6 was notably lower but that of CELF1 was higher in glioma tissues. Survival analysis using the GEPIA database revealed that high transcript levels of CELF1 were associated with unfavourable OS in all patients with LGG. Conversely, high CELF3/4/5 levels predicted favourable OS in these patients. Conclusion This study implied that CELF1/3/4/5 are new prognostic markers and potential therapeutic targets for LGG.

Cytochrome P450 1B1 (CYP1B1) is highly expressed in a variety of tumors and implicated to drug resistance. More and more researches have suggested that CYP1B1 is a new target for cancer prevention and therapy. Various CYP1B1 inhibitors with a rigid polycyclic skeleton have been developed, such as flavonoids, trans-stilbenes, and quinazolines. To obtain a new class of CYP1B1 inhibitors, we designed and synthesized a series of bentranil analogues, moreover, IC

China has become one of the countries with the most severe smog pollution, especially in winter. Many local governments had to take various measures to combat the smog. The driving restriction is one of the policies being widely implemented throughout the country, but the actual effect has been controversial. Over 30 cities in China adopted the driving restriction policy in winter specifically in recent years. In this study, regression discontinuity (RD) method is applied to 16 cities to study whether the policy was effective or not and to find out the reason behind. It is found that (1) the effect has shown differences in different cities, in Cangzhou, Linfen and Shijiazhuang, the policy was effective on winter smog control, while it was ineffective in Luoyang, Tangshan, Xinyang and Zhoukou. (2) High proportion of secondary industry in GDP and inconvenient public transport system has inhibitory effect on the effectiveness of the driving policy. (3) Population density, GDP, the proportion of urban green area and driving restriction intensity have no significant impact on the effectiveness of the driving restriction policy. (4) In terms of meteorological factors, average temperature, rainfall, wind speed and air pressure have a negative impact on PM2.5, while humidity has a positive impact on PM2.5.

Prior to the emergence of the Omicron variant, many cities in China had been able to maintain a “Zero-COVID” policy. They were able to achieve this without blanket city-wide lockdown and through widespread testing and an extensive set of nonpharmaceutical interventions (NPIs), such as mask wearing, contact tracing, and social distancing. We wanted to examine the effectiveness of such a policy in containing SARS-CoV-2 in the early stage of the pandemic. Therefore, we developed a fully stochastic, spatially structured, agent-based model of SARS-CoV-2 ancestral strain and reconstructed the Beijing Xinfadi outbreak through computational simulations. We found that screening for symptoms and among high-risk populations served as methods to discover cryptic community transmission in the early stage of the outbreak. Effective contact tracing could greatly reduce transmission. Targeted community lockdown and temporal mobility restriction could slow down the spatial spread of the virus, with much less of the population being affected. Population-wide mass testing could further improve the speed at which the outbreak is contained. Our analysis suggests that the containment of SARS-CoV-2 ancestral strains was certainly possible. Outbreak suppression and containment at the beginning of the pandemic, before the virus had the opportunity to undergo extensive adaptive evolution with increasing fitness in the human population, could be much more cost-effective in averting the overall pandemic disease burden and socioeconomic cost.

SummaryBackgroundIn early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai.MethodsWe extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmacological interventions. The epidemic was divided into three phases: i) sporadic infections (January 1–February 28), ii) local transmission (March 1–March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt).FindingsA surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest coronavirus disease 2019 (COVID-19) outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai. The spatial distribution of the infections was highly heterogeneous, with 40% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 544 to 325 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak.InterpretationOur results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for successfully containing Omicron outbreaks.FundingKey Program of the National Natural Science Foundation of China (82130093).Research in contextEvidence before this studyOn May 24, 2022, we searched PubMed and Europe PMC for papers published or posted on preprint servers after January 1, 2022, using the following query: (“SARS-CoV-2” OR “Omicron” OR “BA.2”) AND (“epidemiology” OR “epidemiological” OR “transmission dynamics”) AND (“Shanghai”). A total of 26 studies were identified; among them, two aimed to describe or project the spread of the 2022 Omicron outbreak in Shanghai. One preprint described the epidemiological and clinical characteristics of 376 pediatric SARS-CoV-2 infections in March 2022, and the other preprint projected the epidemic progress in Shanghai, without providing an analysis of field data. In sum, none of these studies provided a comprehensive description of the epidemiological characteristics and spatiotemporal transmission dynamics of the outbreak.Added value of this studyWe collected individual information on SARS-CoV-2 infection and the timeline of the public health response. Population-based screenings were repeatedly implemented during the outbreak, which allowed us to investigate the spatiotemporal spread of the Omicron BA.2 variant as well as the impact of the implemented interventions, all without enduring significant amounts of underreporting from surveillance systems, as experienced in other areas. This study provides the first comprehensive assessment of the Omicron outbreak in Shanghai, China.Implications of all the available evidenceThis descriptive study provides a comprehensive understanding of the epidemiological features and transmission dynamics of the Omicron outbreak in Shanghai, China. The empirical evidence from Shanghai, which was ultimately able to curtail the outbreak, provides invaluable information to policymakers on the impact of the containment strategies adopted by the Shanghai public health officials to prepare for potential outbreaks caused by Omicron or novel variants.

The implementation of the agricultural insurance policy and advancement of agricultural technology has great significance for the development of the agricultural economy of China, and it is an important source of national stability and modernization and development of the agriculture sector. Agricultural insurance policy uses the expansion of agricultural technology progress in the process of evaluation, investigation and claims settlement, and so on. Agricultural technology progress is effective in the reduction of some agricultural risks, it also affects farmers’ agricultural insurance behaviors, and optimizes the operating environment of agricultural insurance. The objective of this research is to explore the relationship between agricultural technology progress, agricultural insurance and farmers’ income. It also explains the mutual/cooperative relationship between agricultural technology progress and agricultural insurance. It provides the theoretical basis and data support to verify the promotion effect of agricultural insurance and agricultural technology progress on farmers’ income. This gives the improvement path for alleviating the spatial imbalance of China’s agricultural development. Keeping in view the aforementioned background and this research explores the effects of agricultural technological progress and agricultural insurance on the farmers’ income level. The panel data used for this research were from 2004 to 2019 and were grouped into two parts: high-density agricultural insurance areas and low-density agricultural insurance areas. The relationship between agricultural technology progress, agricultural insurance and farmers’ income was estimated using the Panel Vector Autoregressive (PVAR) model. The results revealed that: (i) both agricultural technology progress and agricultural insurance have a positive effect on the farmers’ income level, but this effect varies across regions; (ii) impact of the agricultural insurance on farmers’ income is greater than the impact of agricultural technology progress on farmers’ income; and (iii) the role of agricultural insurance in promoting agricultural technology progress exists only in areas with high-density agricultural insurance. Therefore, when formulating policies, the policymakers should consider regional differences and characteristics, and adopt development models keeping in view regional variations in adaptability with different agricultural insurance densities, Moreover, they should improve agricultural security policies, optimize agricultural capital allocation, promote the transformation of the agricultural economy from extensional growth to connotative growth, and further improve the agricultural productive income of rural residents.

Background: The infiltration of macrophages in white adipose tissue (WAT) is associated with the development of obesity. A recent study reported that sympathetic neuron–associated macrophages (SAMs) had a pro-inflammatory effect by regulating the metabolism of norepinephrine (NE) in obesity. SAMs transport and degrade NE via solute carrier family 6 member 2（SLC6A2）and monoamine oxidase A（MAOA）respectively. NE has a well-established role in promoting lipolysis in adipocytes. Furthermore, SAMs are recruited and activated in obesity, but the exact molecular mechanism is still unclear. The aim of this study is to explore whether the restraint of SLC6A2 or MAOA by SLC6A2 inhibitor (SLC6A2i) or MAOA inhibitor (MAOAi) would rescured metabolic disorders by modulating NE level in high fat diet (HFD) induced obesity mice model. We thus unveiled the effect of NE on glycolipid metabolism, focusing on the contribution of SAMs .Methods: 24 male C57BL/6J mice (5 weeks old) were randomly fed with normal chow diet (NCD, n=6) or HFD (n=18) respectively for 16 weeks. 18 mice fed with HFD were randomly categorized into 3 groups as follows: HFD+NaCl (n=6), HFD+SLC6A2i (n=6) and HFD+MAOAi (n=6). The body weight, length and serum analysis (glucose, lipidprofile, and insulin) were obtained before and after 3 weeks of NE intervention. Then, superior cervical ganglia(SCG), visceral white adipose tissue (vWAT) and subcutaneous white adipose tissue (sWAT) were extracted for further analysis. Results: After 3 weeks NE intervention, Lee’s index, FBG, P2hBG, TG, TC, LDL-C, and insulin showed lower in HFD+SLC6A2i and HFD+MAOAi group, and HDL-C showed higher than those in HFD+NaCl group (p SAMs proportion, expression of SLC6A2, MAOA, TLR4, MYD88, NF-κB, TNF-α and IL-1α were significantly lower in HFD+SLC6A2i and HFD+MAOAi group (ppConclusion: Our results indicated restraint the function of SLC6A2 or MAOA would rescued metabolic disorders and obesity by modulating NE level. Recruited SAMs in obesity might be derived from the chronic low grade inflammation via TLR4/NF-κB signaling pathway. These findings provide new target for therapeutic potential of glycolipid metabolism and obesity.

Cu-based and Fe-based zeolites are promising catalysts for NH

The eastern slope of the Tibetan Plateau is a crucial corridor of water-vapor transport from the Tibetan Plateau to Eastern China. This is also a region with active cloud initiation, and the locally hatched cloud systems have a profound impact on the radiation budget and hydrological cycle over the downstream Sichuan Basin and the middle reach of the Yangtze River. It is noteworthy that there is a strong diversification in the characteristics and evolution of the ESTP cloud systems due to the complex terrain. Therefore, in this study, ground-based Ka-band millimeter-wave cloud radar measurements collected at the Ganzi (GZ), Litang (LT), Daocheng (DC), and Jiulong (JL) sites of the ESTP in 2019 were analyzed to compare the vertical structures of summer nonprecipitating clouds, including cloud occurrence frequency, radar reflectivity factor, cloud base height, cloud top height, and cloud thickness. The occurrence frequency exhibits two peaks on the ESTP with maximum values of ~20% (2–4 km) and 15% (7–9 km), respectively. The greatest (smallest) occurrence frequency occurs in the JL (GZ). The cloud occurrence frequency of all sites increases rapidly in the afternoon, and the occurrence frequency of the DC presents larger values at 2–4 km. In contrast, the occurrence frequency in the JL shows another increase from 2000 LT to midnight at 7–11 km. Stronger radar echoes occur most frequently in the LT at 5–7 km, and hydrometeor sizes and phase states vary dramatically in mixed-phase clouds. A small number of radar echoes occur at midnight in the JL. A characteristic bimodality of the cloud base height and top height for single-layer, double-layer, and triple-layer clouds was observed. Clouds show a higher base height in the GZ and higher top height in the JL. The ESTP is dominated by thin clouds with thicknesses of 200–400 m. The cloud base height, top height, and thickness exhibit an increase in the afternoon, and higher top height occurs more frequently from midnight to the next early morning in the JL because of its mountain-valley terrain.

Understanding the impact of climate change on tropical cyclones (TCs) has become a hot topic. The slowdown of TC translation speed contributes greatly to the locally accumulated TC damage. While the recent observational evidence shows that TC translation speed has decreased globally by 10% since the mid-twentieth century, the robustness of the trend is questioned by other studies as effects of changes in observational capability can strongly affect the global trend. Moreover, none of the published studies considered dependence of TC slowdown on TC intensity. This is the caveat of these analyses as the effect of TC slowdown is closely related to TC intensity. Here, we investigate the relationship between TC translation speed trend and TC intensity, and reveal possible reasons for the trend. We show that the global slowing trend without weak TC moments (≤ 17 m s-1) is about double of that with weak TC moments in a recent study. This is because the slowing trend is dominated by strong TCs’ trend. Stronger (weaker) TCs tend to be controlled more by upper-level (lower-level) steering flow, and the calculated trend of upper-level steering flow is much larger than that of lower-level steering flow. This may be an important reason for the large difference between the slowing trend without weak TC moments and that with weak TC moments. Furthermore, the changes of TC tracks (including inter-basin trend and latitudinal shift), which are partly attributed to data inhomogeneity, make a much larger contribution to the slowing trend, compared with the weakening of tropical circulation, which is related to anthropogenic warming.

Objective To explore the targets and signaling pathways of flavanomarein in the treatment of non-alcoholic fatty liver disease (NAFLD) by network pharmacology, and to investigate the effect and mechanisms in the treatment. Methods ① The potential active targets of flavanomarein were retrieved in the Swiss Target Prediction database, and the disease-related targets were searched in the DisGeNET database. The prediction targets of lipid metabolism of NAFLD regulated by flavanomarein was obtained through Venn analysis. The Biso Genet database was used to construct the protein-protein interaction (PPI) network diagram, the Metascape database was used to analyze GO functional enrichment and KEGG pathway enrichment, and the Cytoscape software was used to draw the "target-pathway" network diagram. ② NAFLD db/db mice was employed for in vivo verification. Thirty male db/db mice were randomly divided into db/m group, db/db model group, and db/db+flavanomarein group (50 mg/kg). After the administration of 0.5% sodium carboxymethyl cellulose solution and flavanomarein for 12 weeks, the mice were sacrificed, and the liver contents of TG, GSH and GSSG was detected. HE staining and oil red O staining were used to observe the pathological changes of the liver. qRT-PCR and Western blotting were used to detect the mRNA and protein levels of key molecules in the lipid metabolism in the liver. ③HepG2 cells were treated with free fatty acids (FFAs, oleic acid∶palmitic acid =2∶1) and divided into normal group, FFAs treatment group (500 μmol/L), and FFAs+ low, medium and high concentrations of flavanomarein (25, 50, 100 μmol/L) for 24 h. Oil red O staining was used to detect the TG content in HepG2 cells. qRT-PCR and Western blotting were used to detect the mRNA and protein levels of key molecules in the lipid metabolism of HepG2 cells. Results ① A total of 29 core targets of flavanomarein docking NAFLD were screened through Venn analysis, including peroxisome proliferator-activated receptor-gamma (PPARγ), vascular endothelial growth factor (VEGF), and mitogen-activated protein kinase 14 (MAPK14). The GO analysis enriched 6 molecular functions, 20 biological processes and 5 cellular components. KEGG analysis enriched 40 key signaling pathways related to the effect of flavanomarein on NAFLD, which mainly focuses on the AMPK lipid metabolism pathway, insulin resistance (IR) pathway, and apoptosis pathway. ② The results of animal experiments showed that flavanomarein treatment reduced TG level in the NAFLD mice (P < 0.05) and improved the ratio of GSH/GSSG (P < 0.05). HE and oil red O staining showed that flavanomarein could reverse hepatocyte enlargement and reduce lipid drop infiltration of hepatocytes. qRT-PCR results showed that the treatment decreased the mRNA levels of ACC1, SCD1, and FASN for lipid synthesis (P < 0.05), while increased those of ACOX-1 and CPT1α for β-oxidation (P < 0.05). Western blot assay results indicated that the expression levels of SREBP and FASN were obviously lower (P < 0.05), and those of PPARγ and PPARα were increased (P < 0.05) in the flavanomarein group than the model group. ③ In vitro cell experiments showed that flavanomarein reduced the TG content of HepG2 cells (P < 0.05) and the expression of SREBP, SCD1 and ACC1, but increased the levels of CPT1α and ACOX-1 mRNA (P < 0.05). And, the protein expression of SREBP and FASN was also significantly reduced (P < 0.05). Conclusion Flavanomarein may play a therapeutic role in NAFLD by improving oxidative stress, up-regulating fatty acid β-oxidation, reducing lipid synthesis through regulating the PPARγ/SREBP/FASN signaling pathway.

Kashin–Beck disease (KBD) is an endemic disease in China with the highest incidence rate in Tibet region. Promoted generation of oxygen free radicals by semiquinone structure of humic substance (HS) in drinking water was considered to be one of its pathogeneses. Therefore, detailed analysis of HS was performed in water and sediment samples collected from three endemic and three disease-free areas in Changdu Region, Tibet, China. After purification of the HS in the samples, the fractions of HS were characterized using electron paramagnetic resonance, 13C nuclear magnetic resonance, fluorescence spectroscopy with parallel factor analysis and Fourier transform infrared spectroscopy (FTIR). The organic carbon content of HS did not show a significant difference between endemic and disease-free areas or correlation with KBD-associated morbidity. Except FTIR, all techniques succeeded in characterization of the quinone redox system, indicating their validity and consistency. The quinone redox system in aquatic HS exhibited significantly higher level of the following indexes in endemic areas than disease-free areas: semiquinone radical content of fulvic acid (FA) (p

As the risk of harmful environmental exposure is increasing, it is important to find suitable targets for the diagnosis and treatment of the diseases caused. Isocitrate dehydrogenase 2 (IDH2) is an enzyme located in the mitochondria; it plays an important role in numerous cell processes, including maintaining redox homeostasis, participating in the tricarboxylic acid cycle and indirectly taking part in the transmission of the oxidative respiratory chain. IDH2 mutations promote progression in acute myeloid leukemia, glioma and other diseases. The present review mainly summarizes the role and mechanism of IDH2 with regard to the biological effects, such as the mitophagy and apoptosis of animal or human cells, caused by environmental pollution such as radiation, heavy metals and other environmental exposure factors. The possible mechanisms of these biological effects are described in terms of IDH2 expression, reduced nicotine adenine dinucleotide phosphate content and reactive oxygen species level, among other variables. The impact of environmental pollution on human health is increasingly attracting attention. IDH2 may therefore become useful as a potential diagnostic and therapeutic target for environmental exposure-induced diseases.

Siglec-7 (sialic acid–binding immunoglobulin-like lectin 7) is an immune checkpoint-like glycan recognition protein on natural killer (NK) cells. Cancer cells often upregulate Siglec ligands to subvert immunosurveillance, but the molecular basis of Siglec ligands has been elusive. In this study, we investigated Siglec-7 ligands on chronic lymphocytic leukemia (CLL) B cells. CLL B cells express higher levels of Siglec-7 ligands compared with healthy donor B cells, and enzymatic removal of sialic acids or sialomucins makes them more sensitive to NK cell cytotoxicity. Gene knockout experiments have revealed that the sialyltransferase ST6GalNAc-IV is responsible for the biosynthesis of disialyl-T (Neu5Acα2–3Galβ1–3[Neu5Acα2–6]GalNAcα1–), which is the glycotope recognized by Siglec-7, and that CD162 and CD45 are the major carriers of this glycotope on CLL B cells. Analysis of public transcriptomic datasets indicated that the low expression ofGCNT1(encoding core 2 GlcNAc transferase, an enzyme that competes against ST6GalNAc-IV) and high expression ofST6GALNAC4(encoding ST6GalNAc-IV) in CLL B cells, together enhancing the expression of the disialyl-T glycotope, are associated with poor patient prognosis. Taken together, our results determined the molecular basis of Siglec-7 ligand overexpression that protects CLL B cells from NK cell cytotoxicity and identified disialyl-T as a potential prognostic marker of CLL.

In recent years, studies have shown that exposure to environmental pollutants (e.g., radiation, heavy metal substances, air pollutants, organic pollutants) is a leading cause of human non-communicable diseases. The key to disease prevention is to clarify the harmful mechanisms and toxic effects of environmental pollutants on the body. Metabolomics is a high-sensitivity, high-throughput omics technology that can obtain detailed metabolite information of an organism. It is a crucial tool for gaining a comprehensive understanding of the pathway network regulation mechanism of the organism. Its application is widespread in many research fields such as environmental exposure assessment, medicine, systems biology, and biomarker discovery.Recent findings show that metabolomics can be used to obtain molecular snapshots of organisms after environmental exposure, to help understand the interaction between environmental exposure and organisms, and to identify potential biomarkers and biological mechanisms.This review focuses on the application of metabolomics to understand the biological effects of radiation, heavy metals, air pollution, and persistent organic pollutants exposure, and examines some potential biomarkers and toxicity mechanisms.

Background The SARS-CoV-2 containment strategy has been successful in mainland China prior to the emergence of Omicron. However, in the era of highly transmissible variants, whether it is possible for China to sustain a local containment policy and under what conditions China could transition away from it are of paramount importance at the current stage of the pandemic. Methods We developed a spatially structured, fully stochastic, individual-based SARS-CoV-2 transmission model to evaluate the feasibility of sustaining SARS-CoV-2 local containment in mainland China considering the Omicron variants, China’s current immunization level, and nonpharmaceutical interventions (NPIs). We also built a statistical model to estimate the overall disease burden under various hypothetical mitigation scenarios. Results We found that due to high transmissibility, neither Omicron BA.1 nor BA.2 could be contained by China’s pre-Omicron NPI strategies which were successful prior to the emergence of the Omicron variants. However, increased intervention intensity, such as enhanced population mobility restrictions and multi-round mass testing, could lead to containment success. We estimated that an acute Omicron epidemic wave in mainland China would result in significant number of deaths if China were to reopen under current vaccine coverage with no antiviral uptake, while increasing vaccination coverage and antiviral uptake could substantially reduce the disease burden. Conclusions As China’s current vaccination has yet to reach high coverage in older populations, NPIs remain essential tools to maintain low levels of infection while building up protective population immunity, ensuring a smooth transition out of the pandemic phase while minimizing the overall disease burden.

For 99mTc-sestamibi parathyroid single photon emission computed tomography/computed tomography (SPECT/CT), the traditional full-arc 360° acquisition technique has been suggested but not the theoretically low tissue-attenuated anterior 180° method. We aimed to compare the diagnostic performances and target-to-background ratios of anterior 180° and 360° SPECT/CT imaging. Ninety-nine patients who underwent 99mTc-sestamibi scintigraphy and received a surgical–pathological diagnosis of parathyroid adenoma or hyperplasia were enrolled. The SPECT/CT reconstructed images with anterior 180° and full-arc 360° data were interpreted by two physicians using a scoring scale, and the lesions were semi-quantified using target-to-background ratios for both image sets. In total, 113 abnormal parathyroid lesions were identified on the SPECT/CT images. The agreements of interpretation between the two image sets and readers were very good (κ value: 0.83–1.00). The accuracies of summative interpretation for the anterior 180° and full-arc 360° SPECT/CT were 83.04% and 82.46%, respectively. The target-to-background ratios were significantly higher for the anterior 180° than the full-arc 360° images (P

Tisagenlecleucel is a CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and adults with non-Hodgkin lymphoma (NHL). The initial experience with tisagenlecleucel in a real-world setting from a cellular therapy registry is presented here. As of January 2020, 511 patients were enrolled from 73 centers, and 410 patients had follow-up data reported (ALL, n = 255; NHL, n = 155), with a median follow-up of 13.4 and 11.9 months for ALL and NHL, respectively. Among patients with ALL, the initial complete remission (CR) rate was 85.5%. Twelve-month duration of response (DOR), event-free survival, and overall survival (OS) rates were 60.9%, 52.4%, and 77.2%, respectively. Among adults with NHL, the best overall response rate was 61.8%, including an initial CR rate of 39.5%. Six-month DOR, progression-free survival, and OS rates were 55.3%, 38.7%, and 70.7%, respectively. Grade ≥3 cytokine release syndrome and neurotoxicity were reported in 11.6% and 7.5% of all patients, respectively. Similar outcomes were observed in patients with in-specification and out-of-specification products as a result of viability

Background. It is generally considered that traditional Chinese medicine (TCM) therapy postpones the progression of some chronic kidney diseases (CKDs). Chinese medicine herbs are widely applied in TCM therapy. We aimed to evaluate clinical efficacy and safety of Chinese herbal formula granules in patients with CKD stage 3 through a prospective randomized controlled study. Methods. A total of 343 participants with CKD stage 3 were recruited from 9 hospitals in Jiangsu Province between April 2014 and October 2016. Participants were randomly assigned to a treatment or control group. Patients in the treatment group orally took Chinese herbal formula granules twice a day, while controls received placebo granules. The duration of intervention was 24 weeks. Primary outcomes were 24-hour proteinuria, serum creatinine, and eGFR, which were measured every 4 weeks. Results. There was no statistical difference in 24-hour proteinuria between the two groups (0.97 ± 1.14 g/d vs. 0.97 ± 1.25 g/d). Patients in the treatment group had significantly lower serum creatinine level (130.78 ± 32.55 μmol/L versus 149.12 ± 41.27 μmol/L) and significantly higher eGFR level (55.74 ± 50.82 ml/min/1.73·m2 versus 44.46 ± 12.60 ml/min/1.73·m2) than those in the control group ( P