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Abstract Breast cancer therapy has significantly advanced by targeting the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway. BMS-202 (a smallmolecule PD-L1 inhibitor) induces PD-L1 dimerization to block PD-1/PD-L1 interactions, allowing the T-cell-mediated immune response to kill tumor cells. However, immunotherapy alone has limited effects. Clinically approved photodynamic therapy (PDT) activates immunity and selectively targets malignant cells. However, PDT aggravates hypoxia, which may compromise its therapeutic efficacy and promote tumor metastasis. We designed a tumor-specific delivery nanoplatform of liposomes that encapsulate the hypoxia-sensitive antitumor drug tirapazamine (TPZ) and the small-molecule immunosuppressant BMS. New indocyanine green (IR820)-loaded polyethylenimine-folic acid (PEI-FA) was complexed with TPZ and BMS-loaded liposomes via electrostatic interactions to form lipid nanocomposites. This nanoplatform can be triggered by near-infrared irradiation to induce PDT, resulting in a hypoxic tumor environment and activation of the prodrug TPZ to achieve efficient chemotherapy. The in vitro and in vivo studies demonstrated excellent combined PDT, chemotherapy, and immunotherapy effects on the regression of distant tumors and lung metastases, providing a reference method for the preparation of targeted agents for treating breast cancer. Graphical abstract

IntroductionLimited data were available on the effectivenessfour years after Homo or Hetero prime-boost with 10 μg Hansenulapolymorpha recombinant hepatitis B vaccine (HepB-HP) and 20 μgChinese hamster ovary cell HepB (HepB-CHO).MethodsA crosssectional study was performed in maternalhepatitis B surface antigen (HBsAg)-negative children whoreceived one dose of 10 μg HepB-HP at birth, Homo or Heteroprime-boost with 10 μg HepB-HP and 20 μg HepB-CHO at 1 and 6months. HBsAg and hepatitis B surface antibody (anti-HBs) fouryears after immunization were quantitatively detected by achemiluminescent microparticle immunoassay (CMIA).ResultsA total of 359 children were included; 119 childrenreceived two doses of 10 μg HepB-HP and 120 children receivedtwo doses of 20 μg HepB-CHO, called Homo prime-boost; 120children received Hetero prime-boost with 10 μg HepB-HP and 20μg HepB-CHO. All children were HBsAg negative. The geometricmean concentration (GMC) and overall seropositivity rate (SPR) ofanti-HBs were 59.47 (95%CI: 49.00 – 72.16) mIU/ml and 85.51%(307/359). Nearly 15% of the study subjects had an anti-HBsconcentration < 10 mIU/ml and 5.01% had an anti-HBsconcentration ≤ 2.5 mIU/ml. The GMC of the 20 μg CHO Homoprime-boost group [76.05 (95%CI: 54.97 – 105.19) mIU/ml] washigher than that of the 10 μg HP Homo group [45.86 (95%CI:31.94 – 65.84) mIU/ml] (p = 0.035). The GMCs of the Heteroprime-boost groups (10 μg HP-20 μg CHO and 20 μg CHO-10 μgHP) were 75.86 (95% CI: 48.98 – 107.15) mIU/ml and 43.65(95%CI: 27.54 – 69.18) mIU/ml, respectively (p = 0.041). Aftercontrolling for sex influence, the SPR of the 20 μg CHO Homoprime-boost group was 2.087 times than that of the 10 μg HPHomo group.DiscussionThe HepB booster was not necessary in the generalchildren, Homo/Hetero prime-boost with 20 μg HepB-CHO wouldincrease the anti-HBs concentration four years after immunization,timely testing and improved knowledge about the self-pay vaccinewould be good for controlling hepatitis B.

BackgroundHemorrhagic fever with renal syndrome (HFRS) is one of the 10 major infectious diseases that jeopardize human health and is distributed in more than 30 countries around the world. China is the country with the highest number of reported HFRS cases worldwide, accounting for 90% of global cases. The incidence level of HFRS in Quzhou is at the forefront of Zhejiang Province, and there is no specific treatment for it yet. Therefore, it is crucial to grasp the epidemiological characteristics of HFRS in Quzhou and establish a prediction model for HFRS to lay the foundation for early warning of HFRS.MethodsDescriptive epidemiological methods were used to analyze the epidemic characteristics of HFRS, the incidence map was drawn by ArcGIS software, the Seasonal AutoRegressive Integrated Moving Average (SARIMA) and Prophet model were established by R software. Then, root mean square error (RMSE) and mean absolute error (MAE) were used to evaluate the fitting and prediction performances of the model.ResultsA total of 843 HFRS cases were reported in Quzhou City from 2005 to 2022, with the highest annual incidence rate in 2007 (3.93/100,000) and the lowest in 2022 (1.05/100,000) (P trend

Trace elements (TEs) are essential for the treatment of rheumatoid arthritis (RA). This study aimed to prepare a TEs solution enriched with various organic states to evaluate its preventive, therapeutic effects, and mechanism of action in RA and to provide a treatment method for RA treatment. The TEs in natural ore were extracted and added to 0.5% (W/V) L-alanyl-L-glutamine (LG) to obtain a TEs solution (LG-WLYS), which was examined for its concentration and quality. The antioxidant properties and effects of LG-WLYS on cell behavior were evaluated at the cellular level. The preventive and therapeutic effects and mechanism of action of LG-WLYS in rats with RA were explored. The LG-WLYS solution was clear, free from visible foreign matter, and had a pH of 5.33 and an osmolality of 305.67 mOsmol/kg. LG-WLYS inhibited cell migration and angiogenesis. LG-WLYS solution induced macrophages to change from M1-type to M2-type, increased the content of antioxidant enzymes (glutathione, superoxide dismutase, and IL-10), decreased the levels of nitric oxide, malondialdehyde, TNF-α, IL-1β, IL-6, COX-2, and iNOs, scavenging reactive oxygen species from the lesion site, inhibiting the apoptosis of chondrocytes, regulating inflammatory microenvironment, and decreasing inflammation response to exert the therapeutic effect for RA. In conclusion, LG-WLYS has outstanding therapeutic and preventive effects against RA and has enormous potential for further development.

Abstract Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri‐cross‐linked inflammatory microenvironment‐responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment‐responsive hydrogel (OD‐PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano‐fillers into the hydrogel results in extra cross‐linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)/pH dual responsive hydrogel with a triple‐network is achieved. The hydrogel has injectable, self‐healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli‐responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH‐regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K/AKT/NF‐κB and MAPK pathways, exerting anti‐inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple‐network structure provides an effective strategy to treat IDs, holding great promise in clinical application.

We have developed an ovarian cancer-targeted drug delivery system based on a follicle-stimulating hormone receptor (FSHR) peptide. The lipophilic chemotherapeutic drug SN38 and the photosensitizer IR820 were loaded into the phospholipid bilayer of liposomes. The combination of chemotherapy and phototherapy has become a promising strategy to improve the therapeutic effect of chemotherapy drugs on solid tumors. IR820 can be used for photodynamic therapy (PDT), effectively converting near-infrared light (NIR) into heat and producing reactive oxygen species (ROS), causing damage to intracellular components and leading to cell death. In addition, PDT generates heat in near-infrared, thereby enhancing the sensitivity of tumors to chemotherapy drugs. FSH liposomes loaded with SN38 and IR820 (SN38/IR820-Lipo@FSH) were prepared using thin-film hydration-sonication. FSH peptide binding was analyzed using 1H NMR spectrum and Maldi-Tof. The average size and zeta potential of SN38/IR820-Lipo@FSH were 105.1 ± 1.15 nm (PDI: 0.204 ± 0.03) and −27.8 ± 0.42 mV, respectively. The encapsulation efficiency of SN38 and IR820 in SN38/IR820-Lipo@FSH liposomes were 90.2% and 91.5%, respectively, and their release was slow in vitro. FSH significantly increased the uptake of liposomes, inhibited cell proliferation, and induced apoptosis in A2780 cells. Moreover, SN38/IR820-Lipo@FSH exhibited better tumor-targeting ability and anti-ovarian cancer activity in vivo when compared with non-targeted SN38/IR820-Lipo. The combination of chemotherapy and photodynamic treatment based on an FSH peptide-targeted delivery system may be an effective approach to treating ovarian cancer.

Abstract As the crucial dimension (CD) of logic circuits continues to shrink, the photoresist metrics, including resolution, line edge roughness, and sensitivity, are faced with significant challenges. Photoresists are indispensable in the integrated circuit manufacturing industry, and specifically in achieving smaller critical dimensions. In this study, the effects of two categories of photosensitive compounds on lithography performance are explored, through a series of sulfonium salt‐based photoacid generators (PAGs) with diverse reactivity and photodegradable nucleophiles (PDNs) with varying nucleophilicity. The detailed characterization and exposure experiments suggest that the reactive alterations of different PAGs are mostly associated with the amount of phenyl composed of cations in PAGs. The “PDN first, PAG second” strategy, which employs a combination of low reactivity PAG and high reactivity PDN and involves PDN decomposition first and PAG decomposition second in the electron beam lithography process, achieves high sensitivity (100–270 µC cm−2), high resolution (25 nm 1:1 line/space, L/S), and low line edge roughness (LER ≤ 3.3 nm) stripes. This approach outperforms conventional formulations and may provide a potentially effective and useful strategy to improve electron beam photoresists.

A keloid is a benign tumor manifested as abnormal fibroplasia on the surface of the skin. Curing keloids has become a major clinical challenge, and searching for new treatments and medications has become critical. In this study, we developed a LA67 liposome-loaded thermo-sensitive hydrogel (LA67-RL-Gel) with active targeting for treating keloids via peritumoral injection and explored the anti-keloid mechanism. Firstly, Arg-Gly-Asp (RGD) peptide-modified liposomes (LA67-RL) loaded with LA67 were prepared with a particle size of 105.9 nm and a Zeta potential of −27.4 mV, and an encapsulation efficiency of 89.6 ± 3.7%. We then constructed a thermo-sensitive hydrogel loaded with LA67-RL by poloxamer 407 and 188. The formulation was optimized through the Box–Behnken design, where the impact of the proportion of the ingredients on the quality of the hydrogel was evaluated entirely. The optimal formulation was 20.7% P407 and 2.1% P188, and the gelation time at 37 °C was 9.5 s. LA67-RL-Gel slowly released 92.2 ± 0.8% of LA67 at pH 6.5 PBS for 72 h. LA67-RL-Gel increased adhesion with KF cells; increased uptake; promoted KF cells apoptosis; inhibited cell proliferation; reduced α-SMA content; decreased collagen I, collagen III, and fibronectin deposition; inhibited angiogenesis; and modulated the keloid microenvironment, ultimately exerting anti-keloid effects. In summary, this simple, low-cost, and highly effective anti-keloid liposome hydrogel provides a novel approach for treating keloids and deserves further development.

Limited data are available on the effectiveness of COVID-19 vaccines used in China in real-world outbreaks – especially against Omicron variants in vaccinated individuals. Two outbreaks of SARS-CoV-2 Omicron variants – the first involving the sub-lineage BA.2 and the second the BA.1 variant – occurred in Quzhou. Infected people and their close contacts were divided according to vaccination status: unvaccinated, partially vaccinated, fully vaccinated, and boosted. The Cox proportional-hazard regression model was used to estimate the evolving hazard for vaccinated individuals after their first immunization. 138 people had been infected with the SARS-CoV-2 Omicron BA.2 variant and 13 with the BA.1 variant. Of the 151 infections, 99.34% (150/151) were mild or asymptomatic and 90.07% (136/151) were vaccine breakthrough cases. The total vaccine effectiveness (VE) of partial, full, and booster vaccinations during the two outbreaks was 47.4% (95%CI: 0–93.1%), 28.9% (95%CI: 0–60.2%), and 27.5% (95%CI: 0–58.3%). The VE of booster vaccination against the Omicron BA.1 variant was higher than that for the BA.2 variant. The cumulative hazard began to increase 220 days after the first immunization. The transmissibility of the Omicron BA.2 variant as for BA.1 did not increase in vaccinated individuals; booster vaccination after a primary course substantially increased protection. Our study found that the SARS-CoV-2 Omicron variant caused less severe illness and that the VE of boosters against the Omicron variant was less than 30%. Timely administration of the booster dose was important, especially for individuals aged over 80 years old.

Despite the high coverage of pertussis vaccines in high-income countries, pertussis resurgence has been reported in recent years, and has stimulated interest in the effects of vaccines and vaccination strategies. Immunoglobulin G (IgG) antibodies against pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) after immunization with four doses of co-purified or component vaccines were determined by enzyme-linked immunosorbent assay (ELISA). Serological data of PT-IgG geometric mean concentrations (GMCs) over time since vaccination were used to fit the mathematical models. A total of 953 children were included in this study; 590 participants received four doses of the component acellular vaccine and 363 participants received four doses of the co-purified acellular vaccine. The GMCs and the seropositivity rate of pertussis IgG were significantly influenced by the production methods, and the immunogenicity of the component acellular vaccine was superior to that of the co-purified acellular vaccine. The fitted mathematical models for the component acellular vaccine and the co-purified acellular vaccine were Y=91.20e-0.039x and Y=37.71x-0.493, respectively. The initial GMCs of the component acellular vaccine was higher than that of the co-purified acellular vaccine, but both were similar at 72 months after immunization. Pertussis IgG levels waned over time after four doses of acellular pertussis vaccine, regardless of whether component or co-purified vaccine was used. The development and promotion of component acellular pertussis vaccines should be accelerated in China, and booster doses of pertussis vaccine in adolescents, adults, and pregnant women should be employed.

Mumps cases were reported frequently when a routine dose measles–mumps–rubella(MMR) achieved high coverage in Quzhou. The supplementary immunization activities (SIA) using measles mumps (MM) was conducted to control mumps outbreaks. The effectiveness of one and two doses of mumps-containing vaccine (MuCV) was assessed using surveillance data in this study. Mumps cases and immunization information were retrieved from the National Notifiable Disease Reporting System (NNDRS) and the Zhejiang Provincial Immunization Information System (ZJIIS), respectively. Mumps cases of children born from 2006 to 2010 were included. Vaccine effectiveness by dose was calculated using the screening method. A total of 956 mumps cases were identified, of whom 754 (78.9%) had received one dose of MuCV; 108 (11.3%) had received two doses; 94 (9.8%) were unvaccinated. The coverage of one-dose MuCV in the 2006–2010 birth cohorts ranged from 91.6% to 98.9%. Except the 2009 birth cohort in which the coverage of two doses of MuCV was 55.1%, the others were less than 10%. Vaccine effectiveness (VE) of one dose ranged from 47.4% to 86.0%, while VE of two doses ranged from 64.0% to 92.4%. The VE of one and two doses of MuCV waned over time, but the VE of two doses was consistently higher than that of one dose in the same period. The vaccine schedule with two-dose MMR should be implemented among children in Quzhou. The optimal age for the second dose needs to be further evaluated.

This study aims to investigate healthcare workers’ (HCWs) willingness to receive SARS-CoV-2 vaccine in Zhejiang and to discover the related influential factors. The survey was conducted in six regions of Zhejiang Province, China, and 13 hospitals and 12 Centers for Disease Control and Prevention (CDC) were incorporated into the survey research. Participants were healthcare workers and a total of 3726 questionnaires were collected online, of which 3634 (97.53%) were analyzed. The relationships between the factors and the willingness to get vaccinated against COVID-19 were computed as odds ratios (ORs) by means of multi-factor non-conditional logistic regression analysis. Of the 3634 participants, 2874 (79.09%) HCWs expressed their willingness to get vaccinated if the SARS-CoV-2 vaccine becomes available. Respondents who were younger than 50 years (OR = 1.502, 95% CI: 1.047–2.154), those who believed that they were somewhat likely (OR = 1.658, 95% CI: 1.297–2.120) or likely (OR = 1.893, 95% CI: 1.334–2.684) to get infected by SARS-COV-2 and those with a positive attitude toward the SARS-CoV-2 vaccine were more willing to get vaccinated. Furthermore, compared to doctors, nurses were more reluctant to get vaccinated. In addition, it was found that higher the education level, lower the willingness to get vaccinated. This study revealed that HCWs in Zhejiang Province had a high willingness to get vaccinated. Awareness about the vaccine’s effectiveness and safety and the disease severity should be promoted among HCWs over 50 years of age and nurses to increase the willingness to get vaccinated.

Drug degradation at low pH and rapid clearance from intestinal absorption sites are the main factors limiting the development of oral macromolecular delivery systems. Based on the pH responsiveness and mucosal adhesion of hyaluronic acid (HA) and poly[2-(dimethylamino)ethyl methacrylate] (PDM), we prepared three HA–PDM nano-delivery systems loaded with insulin (INS) using three different molecular weights (MW) of HA (L, M, H), respectively. The three types of nanoparticles (L/H/M-HA–PDM–INS) had uniform particle sizes and negatively charged surfaces. The optimal drug loadings of the L-HA–PDM–INS, M-HA–PDM–INS, H-HA–PDM–INS were 8.69 ± 0.94%, 9.11 ± 1.03%, and 10.61 ± 1.16% (w/w), respectively. The structural characteristics of HA–PDM–INS were determined using FT-IR, and the effect of the MW of HA on the properties of HA–PDM–INS was investigated. The release of INS from H-HA–PDM–INS was 22.01 ± 3.84% at pH 1.2 and 63.23 ± 4.10% at pH 7.4. The protective ability of HA–PDM–INS with different MW against INS was verified by circular dichroism spectroscopy and protease resistance experiments. H-HA–PDM–INS retained 45.67 ± 5.03% INS at pH 1.2 at 2 h. The biocompatibility of HA–PDM–INS, regardless of the MW of HA, was demonstrated using CCK-8 and live–dead cell staining. Compared with the INS solution, the transport efficiencies of L-HA–PDM–INS, M-HA–PDM–INS, and H-HA–PDM–INS increased 4.16, 3.81, and 3.10 times, respectively. In vivo pharmacodynamic and pharmacokinetic studies were performed in diabetic rats following oral administration. H-HA–PDM–INS exhibited an effective hypoglycemic effect over a long period, with relative bioavailability of 14.62%. In conclusion, these simple, environmentally friendly, pH-responsive, and mucoadhesive nanoparticles have the potential for industrial development. This study provides preliminary data support for oral INS delivery.

A low molecular weight organic compound containing bis-phenol A backbone (BPA-6OH) is reported as a negative-tone photoresist. This material has a high glass transition temperature and excellent thermal stability. A good contrast, well-resolved line pattern around 73.4 nm and sensitivity of 52 µC cm−2 can be received for negative-tone molecular glass photoresist upon exposure in electron beam lithography system. It indicates that the negative-tone molecular glass photoresist is one of the promising candidates for use in electron beam lithography.

Photoresists are radiation-sensitive materials used for forming patterns to build up IC devices. To date, most photoresists have been based on organic polymers, which have been dominating the semiconductor industries over the past few decades. It is obvious that extreme ultraviolet (EUV) lithography has become the next-generation lithography technology. The development of comprehensive performance EUV resist is one of the most critical issues. However, organic polymeric photoresists are difficult to meet the harsh requirements of EUV lithography. Pure inorganic photoresists such as metal salts, hydrogen silsesquioxane (HSQ) are expected for EUV lithography due to their high resistance and high resolution. But the low sensitivity makes them not suitable for high volume manufacturing (HVM). Organic-inorganic hybrid photoresists, containing both organic and inorganic components, are regarded as one of the most promising EUV resists. They combine both merits of organic and inorganic materials and have significant advantages in machinability, etching resistance, EUV absorption, and chemical/thermal stability. Organic-inorganic hybrid photoresists are considered as ideal materials for realizing industrial-grade patterns below 10 nm. This review mainly focuses on the development of organic-inorganic hybrid photoresists over the past decade.

Background. From 2005 to 2016, the prevention and control of mumps in China have undergone three stages of transition. These include the use of MuCV as a self-supported vaccine, the introduction of one-dose MMR to the Expanded Program on Immunization (EPI), and the administration of two-dose MuCV following supplementary immunization activities (SIAs) using MM. Here, using surveillance data, we assessed the epidemiology of mumps during the three stages. Methods. Children in Quzhou of China born from 2005 to 2016 and registered in the Zhejiang Provincial Immunization Information System (ZJIIS) were included. We analyzed the epidemic data and calculated incidence and MuCV coverage via birth cohorts. Results. The average incidence of mumps in 2005-2006, 2007-2010, and 2011-2016 was 51.57, 41.02, and 12.53 per 100,000 individuals, respectively. The highest incidence was in children aged 6-14 years from 2005-2016, of which the majority were school students (67.84%). Approximately 90% of the reported outbreaks occurred in school children (primary school/middle school). The seasonal characteristics of mumps were less obvious from 2011 to 2016. The coverage of one-dose MMR in the 2005 birth cohort was 71.38%. For the 2006-2010 birth cohort, the coverage of one-dose MuCV was 96.82% and the coverage of two-dose MuCV was 17.68%. The children born from 2011 to 2016 were only free vaccinated with MMR; the coverage of one-dose MuCV was 99.10%. The mumps incidence in the three birth cohorts significantly declined (X2=805.90, P

Magnetic resonance imaging (MRI) with gadolinium based contrast agents (GBCA) is routinely used in the clinic to visualize lesions in multiple sclerosis (MS). Although GBCA reveal endothelial permeability, they fail to expose other aspects of lesion formation such as the magnitude of inflammation or tissue changes occurring at sites of blood-brain barrier (BBB) disruption. Moreover, evidence pointing to potential side effects of GBCA has been increasing. Thus, there is an urgent need to develop GBCA-independent imaging tools to monitor pathology in MS. Using MR-elastography (MRE), we previously demonstrated in both MS and the animal model experimental autoimmune encephalomyelitis (EAE) that inflammation was associated with a reduction of brain stiffness. Now, using the relapsing-remitting EAE model, we show that the cerebellum—a region with predominant inflammation in this model—is especially prone to loss of stiffness. We also demonstrate that, contrary to GBCA-MRI, reduction of brain stiffness correlates with clinical disability and is associated with enhanced expression of the extracellular matrix protein fibronectin (FN). Further, we show that FN is largely expressed by activated astrocytes at acute lesions, and reflects the magnitude of tissue remodeling at sites of BBB breakdown. Therefore, MRE could emerge as a safe tool suitable to monitor disease activity in MS.

BODIPY dyes, though widely explored, have not been pursued as chromophore reaction based chemical probes. Here, the authors synthesize a meso-naked BODIPY core flanked with two electron-withdrawing groups, which undergoes a reversible change in conjugated structure in the presence of base and functions as a dual signal and ultrahigh turn-on ratio chemical probe.

Liver inflammation and excessive accumulation of lipids play a critical role in alcoholic liver diseases (ALD) pathogenesis. Plant polyphenols are widely used to prevent toxic liver damage. The anthocyanin from Lonicera caerulea L. was extracted and purified. The aim of the study was to evaluate the hepatoprotective mechanism of the purified component (PLE), focusing on the effects of PLE on alcoholic steatohepatitis. C57BL/6 mice were fed on chronic plus binge ethanol in Lieber-DeCarli liquid diet to establish acute ethanol model. PLE treatment significantly reduced the accumulation of serum aminotransferase and triglycerides and increased albumin levels in ethanol-induced mice. Also, PLE ameliorated histological changes and lipid droplets induced by ethanol. In addition, PLE obviously suppressed the expression of SREBP1 and enhanced phosphorylation of AMPK compared with chronic ethanol administration. PLE suppressed inflammasome activation by decreasing F4/80 level and inhibiting caspase-1, thereby preventing activated macrophages from producing pro-inflammation cytokines. AML12 cells were pretreated with different concentrations of PLE for 2 h and then exposed to ethanol for 48 h. PLE suppressed the expression of SREBP1 and enhanced phosphorylation of AMPK in AML12 cells exposed to ethanol. Additionally, PLE inhibited the expression of F4/80 and decreased IL-1β release. AMPK interference confirms that PLE downregulation SREBP1 and F4/80 depending on AMPK activation in ethanol-treated AML12 cells. PLE possessed the capacity for inhibiting the inflammatory response and suppressing lipid accumulation, indicating that PLE can be used as a dietary health supplement for alcoholic steatohepatitis.

Qiangtang Basin is expected to become important strategic petroleum exploitation area in China. However, little research has been done on the Permian strata in this area. This paper presents Lower Permian Zhanjin Formation geochemical data from the Jiaomuri area, reconstructing the paleo-depositional environment and providing information for further petroleum exploration. The geochemical characteristics of 19 samples were investigated. These geochemical samples show a developed mud flat characteristic with light rich clay content. The geological data were used to constrain the paleoredox environment, which proved that these sediments were deposited mainly beneath a slightly oxic water column with relatively low paleoproductivity as evidenced by the P/Ti (mean of 0.07) and Ba/Al (mean of 20.5). Palaeoclimate indexes such as the C-value (0.24-1.75) and Sr/Cu (1.28-11.58) reveal a humid climatic condition during Zhanjin Formation sediment deposition. The ω(La)N/ω(Yb)N ratio values indicate a fast sedimentary rate during the deposition period.