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Extreme snow loads can collapse roofs. This load is calculated based on the ground snow load (that is, the snow water equivalent on the ground). However, snow water equivalent (SWE) measurements are unavailable for most sites, while the ground snow depth is frequently measured and recorded. A new simple practical algorithm was proposed in this study to evaluate the SWE by utilizing ground snow depth, precipitation data, wind speed, and air temperature. For the evaluation, the precipitation was classified as snowfall or rainfall according to the air temperature, the snowfall or rainfall was then corrected for measurement error that is mainly caused by wind-induced undercatch, and the effect of snow water loss was considered. The developed algorithm was applied and validated using data from 57 meteorological stations located in the northeastern region of China. The annual maximum SWE obtained based on the proposed algorithm was compared with that obtained from the actual SWE measurements. The return period values of the annual maximum ground snow load were estimated and compared to those obtained according to the procedure suggested by the Chinese structural design code. The comparison indicated that the use of the proposed algorithm leads to a good estimated SWE or ground snow load. Its use allowed the estimation of the ground snow load for sites without SWE measurement and facilitated snow hazard mapping.

Obesity develops from an imbalance of energy homeostasis and is associated with the development of metabolic disorders, including insulin resistance and type 2 diabetes. Identification of the underlying molecular mechanisms and effective therapeutic approaches is highly needed. Lysine-specific demethylase 1 (LSD1), an flavin adenine dinucletide-dependent amine oxidase, is implicated in a wide variety of biological processes, including tumorigenesis, stem cell fate decisions, and embryonic development. Recent studies have suggested a vital role of LSD1 in regulating adaptive thermogenesis, mitochondrial biogenesis, glucose, and lipid metabolism. More recently, LSD1 activity was found to be regulated by nutrients, energy status, and hormonal signals, suggesting that it may act as a novel sensor for nutritional regulation of metabolic health. Here, we first discuss the effects of LSD1 on physiological phenotypes, including body weight, fat mass, body temperature, and glucose homeostasis. We also summarize recent understanding of the physiological roles and underlying mechanisms of LSD1 in controlling metabolic functions of adipose and other tissues. Hopefully, a better understanding of the roles of LSD1 in metabolic regulation may provide new perspectives for the nutritional prevention and treatment of obesity.

Background: Tripterygium wilfordii Hook F provided the source of the first diterpenoid triepoxide lactone, Triptolide, identified as the primary constituent causing the anticancer activity. So far, it has not been reported whether triptolide has a therapeutic effect on cutaneous squamous cell carcinoma (cSCC). This study investigates the triptolide's therapeutic impact on cSCC both in vitro and in vivo and investigates the triptolide's potential involvement in signaling pathways. Materials and methods: The CCK-8 assays, wound healing assays, and colony formation assays were used to assess the effects of triptolide on the proliferation and migration of cSCC cells. The alteration in gene expression following triptolide treatment was shown by RNA sequencing. Flow cytometry was then applied to evaluate cell apoptosis. Western blot was used to find the associated proteins' expressions. The effectiveness of triptolide was then evaluated in vivo using a xenograft model, and histological staining was employed to determine the visceral toxicity. Results: Triptolide greatly reduces the migratory and proliferative capacity of cSCC cells. Triptolide dramatically decreased cell viability and migration in the A431 and SCL-1 cells compared to the control group, according to the CCK8 assay, wound healing assay, and colony formation assay. Flow cytometry demonstrated that treatment with 10-40 nM triptolide increased apoptosis in a concentration-dependent manner, with a statistically significant difference. Furthermore, mice given triptolide had smaller tumor sizes than those in the control group. Triptolide treatment drastically altered the expression of autophagic and apoptotic proteins. The considerable reduction in the proteins Akt and mTOR levels further illustrated the critical function of triptolide in cSCC. Conclusion: Triptolide caused cSCC cells to engage in autophagy and apoptosis by inhibiting the Akt/mTOR signaling pathways. Triptolide may be a possible antitumor agent for the treatment of cSCC.

Background: We previously found that modified 5-aminolevulinic acid photodynamic therapy (M-PDT) is painless and effective in cutaneous squamous cell carcinoma (cSCC) treatment, however, the regulatory mechanism of M-PDT in cSCC is still unclear.Objective: To clarify the effect and relevant regulatory mechanism of M-PDT in cSCC.Methods: The cSCC apoptosis was examined by flow cytometry, TUNEL staining and Cleaved-caspase-3 immunofluorescence, respectively. The autophagy-related characterization was detected by monodansylcadaverine (MDC) staining, transmission electron microscopy (TEM), GFP-LC3B autophagic vacuoles localization and mRFP-EGFP tandem fluorescence-tagged LC3B construct, respectively. The expression of autophagy-related proteins and Akt/mTOR signaling molecules were examined by Western blot. ROS generation was measured by DCFH-DA probe.Results: We found that M-PDT induced cSCC apoptosis in a dose-dependent manner, and this result was related to autophagic flux blockage. The phenomenon is confirmed by the results that M-PDT could induce autophagosomes accumulation and upregulate LC3-II and p62 expression. M-PDT elevated co-localization of RFP and GFP tandem-tagged LC3B puncta in cSCC cell, reflecting autophagic flux blockage, and this was confirmed by transmission electron microscopy. Furthermore, we noticed that M-PDT induced accumulated autophagosomes-dependent apoptosis via targeting ROS-mediated Akt/mTOR signaling. Suppression of Akt potentiated M-PDT-induced upregulation of LC3-II and p62 levels, whereas Akt activation and ROS inhibition rendered resistance to these events. In addition, we observed that lysosomal dysfunction was involved in M-PDT-triggered accumulated autophagosomes-dependent cSCC apoptosis.Conclusion: Our data demonstrates that M-PDT inhibits cSCC through blocking Akt/mTOR-mediated autophagic flux.

Striae gravidarum (SG) is a kind of dermal scar associated with psychosocial and therapeutic challenge. Topical reagents and non-invasive laser are more preferred than invasive procedures for less pain and shorter downtime. However, there are few studies on comparing and combining these two modalities. The aim of the present study was to evaluate the efficacy and tolerance of a topical regimen containing β-glucan, 1565-nm non-ablative fractional laser (NAFL; ResurFX), and combination of them for SG. A total of 128 unilateral abdomens from 64 subjects were randomly divided into four strategies and were followed up for 12 weeks: topical vehicle (Veh); topical β-glucan (B); 1565-nm NAFL combined topical vehicle (NAFL); 1565-nm NAFL combined topical β-glucan (B + NAFL). NAFL was applied three times with a 4-week interval. Topical reagent was applied b.i.d. for 12 weeks. Global Aesthetic Improvement Scale (GAIS) scores were assessed by blinded physician according to standard photograph, and by subjects at 12th week. The degree of SG atrophy was assessed by blinded physician before treatment and at the 12th week according to a standard 5-point scale. Collagen remodeling was evaluated by histological analysis and all adverse effects were recorded. A total of 56 women (112 unilateral abdomens) completed all study. The GAIS scores by blinded physician showed greater improvement in NAFL as compared with β-glucan, and by subjects showed greater improvement in β-glucan as compared with vehicle. In terms of striae atrophy scale, the improvement of SG atrophy was more prominent in NAFL compared to β-glucan, and in β-glucan + NAFL compared to Veh + NAFL. All treatments were well tolerated. Topical β-glucan regimen can mildly improve SG. NAFL showed better results than topical β-glucan regimen. The combined strategy may further improve the SG atrophy compared with single treatment strategy.

Alginate (ALG) is known to alleviate intestinal inflammation in inflammatory bowel disease, but its mechanism of action remains elusive. In the present study, we studied the involvement of the intestinal microbiota and bile acid (BA) metabolism in ALG-mediated anti-inflammatory effects in mice. A combination of 16S rRNA gene amplicon sequencing, shotgun metagenomic sequencing, and targeted BA metabolomic profiling was employed to investigate structural and functional differences in the colonic microbiota and BA metabolism in dextran sulfate sodium (DSS)-treated mice with or without dietary supplementation of ALG. We further explored the role of the intestinal microbiota as well as a selected ALG-enriched bacterium and BA in DSS-induced colitis. Dietary ALG alleviated DSS-mediated intestinal inflammation and enriched a small set of bacteria including Bifidobacterium animalis in the colon (

Tyrosine-protein phosphatase non-receptor type 1 (Ptpn1) is known to be involved in macrophage polarization. However, whether and how Ptpn1 regulates macrophage phenotype to affect intestinal epithelial barrier function remains largely unexplored. Herein, we investigated the impact of Ptpn1 and macrophage-derived small extracellular vesicles (sEVs) on macrophage-intestinal epithelial cell (IEC) interactions in the context of intestinal inflammation. We found that Ptpn1 knockdown shifts macrophages toward the anti-inflammatory M2 phenotype, thereby promoting intestinal barrier integrity and suppressing inflammatory response in the macrophage-IEC co-culture model. We further revealed that conditioned medium or sEVs isolated from Ptp1b knockdown macrophages are the primary factor driving the beneficial outcomes. Consistently, administration of the sEVs from Ptpn1-knockdown macrophages reduced disease severity and ameliorated intestinal inflammation in LPS-challenged mice. Furthermore, depletion of macrophages in mice abrogated the protective effect of Ptpn1-knockdown macrophage sEVs against Salmonella Typhimurium infection. Importantly, we found lactadherin to be highly enriched in the sEVs of Ptpn1-knockdown macrophages. Administration of recombinant lactadherin alleviated intestinal inflammation and barrier dysfunction by inducing macrophage M2 polarization. Interestingly, sEVs lactadherin was also internalized by macrophages and IECs, leading to macrophage M2 polarization and enhanced intestinal barrier integrity. Mechanistically, the anti-inflammatory and barrier-enhancing effect of lactadherin was achieved by reducing TNF-α and NF-κB activation. Thus, we demonstrated that sEVs from Ptpn1-knockdown macrophages mediate the communication between IECs and macrophages through enrichment of lactadherin. The outcome could potentially lead to the development of novel therapies for intestinal inflammatory disorders.

Floating deep mixed column is an effective ground improvement method to treat soft soils. However, the traditional settlement estimation formula under the assumption of equal strain is not consistent with the actual situation. To investigate the settlement behavior of floating columns, a series of laboratory model tests and finite element analyses were carried out. The results reveal that the degree of consolidation of ground improved by floating columns is 10–20% lower than that of end-bearing columns, and the column–soil ratio of floating column treated ground is between 4 and 8. The settlement of improved layer calculated by equal strain assumption is lower than the measured settlement and the error between them is affected by load intensity, depth improvement ratio, and column–soil modulus ratio of floating columns. A simplified method for the settlement calculation of ground improved by floating columns has been proposed considering influence coefficients. The validity of the method was verified by the cases in the literature.

Unbalanced snow distribution, which leads to an excessive snow load in a local area, is one of the main reasons for building collapses. The formation of uneven snowdrifts is closely related to the shape of the building as it seriously affects the turbulent structure and drifting snow process. Unfortunately, the design codes of different countries for applying snow load on building structures cannot give a clear explanation because of the discrepancies between them. Therefore, a series of reduced scale field measurements of snowdrifts on roofs were conducted to clarify such discrepancies. Firstly, the size effect of model scaling was investigated by observing snowdrifts around two models with a scale ratio of 1/2. The results show that the size effect has little influence on the snowdrift pattern on the premise of satisfying the similarity criterion. Thereafter, the snowdrift characteristics of two-level roofed and gable roofed buildings were explored and analyzed through the comparison with different national load codes and collapsed building cases. Overall, the provisions of the Chinese load code differ from the measurement results, which leads to an underestimation of roof snow load. ISO 4355 and Canadian NBC codes could give a better prediction of the snow load by comparison.

Coronavirus disease 2019 (COVID-19) is a new type of respiratory infectious disease that spreads among humans. People infected with COVID-19 present with severe acute respiratory symptoms, fever, cough, breathlessness and dyspnea, impaired physical conditions, kidney failure, and even death. Chest radiographs suggest diffuse inflammation in both lungs and show "white lung" changes. Patients may even experience multiple organ failures within a short period. The effects of general ventilator-assisted treatment are poor. While the application of extracorporeal membrane oxygenation (ECMO) for adjuvant therapy in COVID-19 patients may benefit, there is still a lack of clinical management experience to guide the treatment of the disease. Therefore, in this case, report, we describe the case of a COVID-19-infected patient who was managed with ECMO. During treatment, the patient's vital signs, biochemical indicators, and hemodynamic changes were closely monitored, with strengthening the operation of ECMO and mechanical ventilation, the patients bleeding, infection and other related complications were actively prevented and managed. After active treatment and careful management, the patient was successfully weaned from ECMO after 13 days. This report has summarized the management experience of a severe case with ECMO management, which can provide a reference for the diagnosis and treatment of severe COVID-19 patients in the future.

Congenital poikiloderma is an extremely rare autosomal dominant genetic syndrome, characterized by a combination of early onset poikiloderma, telangiectasia, and epidermal atrophy. FAM111B gene with multiple mutations has been identified as a potential causative gene for congenital poikiloderma. In this report, we described a boy with congenital poikiloderma confirmed by clinical manifestations. Next-generation sequencing based on a gene probe panel consisting of 541 genetic loci of genodermatoses, was used to screen mutations of the proband and his parents. Results showed that a missense mutation in the FAM111B gene c.1883G>A (rs587777238) was identified in the proband, but absent in his parents, indicating the mutation is de novo. In conclusion, a new case of congenital poikiloderma in China was reported, and the hotspot mutations in codon 628 of FAM111B gene was reviewed, as well as authenticating the uncertain association between genotypes and phenotypes in this rare disease.

Snow sliding of roofs is a threat to the structural safety of roof structures by causing a surcharge of local snow load on the lower roof and may pose a serious threat to pedestrians and vehicles on the ground. Therefore, it is of great significance to study the mechanism of snow sliding on roofs. Under the action of ambient temperature, solar radiation, internal heating of the building, etc., the bottom layer of roof snow is often presented in the form of porous ice after a complicated phase transition of the snow particles. Under this circumstance, the interface between roof snow and the roof can be seen as the contact between porous ice and the roofing material. In order to investigate the initialization of roof snow sliding from the material point of view, the shear performance of the interface between different roofing materials and ice with different porosities was carried out in this study. The effects of different ambient temperatures (−4, −6, and −8°C), different normal stress (0, 50, and 100 kPa), and different ice porosities (represented by the contact area ratio of 1.0, 0.8, and 0.6) on this shear performance were analyzed by direct shear tests. The test results showed that the shear failure between the ice and the roofing material was brittle, and the interface shear strength was affected by the ambient temperature, normal stress, contact area ratio, as well as the material type: the strength increases with the decrease of ambient temperature, the increase of normal stress, the increase of contact area ratio, and the increase of surface roughness of the material. Based on the test results, a quantitative relationship between the interface shear strength and the related factors was given in the article, which provides a useful reference for future experimental or simulation studies on roof snow sliding.

Cutaneous squamous cell carcinoma (CSCC) is one of the most common non-melanoma skin cancers worldwide. Fatty acid-binding protein 7 (FABP7) has been reported to be involved in the occurrence, development, metastasis and prognosis of various tumors. In addition, downregulated FABP7 expression was demonstrated in cutaneous malignant melanoma in a previous study. Therefore, we speculated that FABP7 may be a biomarker for CSCC diagnosis. The aim of the present study was to determine the molecular mechanism underlying the effects of FABP7 in CSCC, which may provide a new diagnostic biomarker or treatment target for CSCC. Reverse transcription-PCR, western blotting and immunohistochemistry assays were performed to detect the expression levels of FABP7 in CSCC tissues and cells. Overexpression of FABP7 was achieved in A431 and colo-16 cell lines by transfection with an overexpression vector (oeFABP7). Cell proliferation, colony formation, migration and invasion were detected by Cell Counting Kit-8, crystal violet, scratch and Transwell assays, respectively. Following FABP7 overexpression, western blotting was used to determine the expression levels of proliferation-, invasion- and Notch pathway-associated proteins, including Snail, N-cadherin, Twist, matrix metalloproteinase (MMP)-2, MMP-7, Notch 1 and Notch 3. In addition a CSCC model in nude mice was constructed. Immunohistochemistry was used to determine the expression levels of FABP7, Ki67, Notch 1 and Notch 3. It was demonstrated that FABP7 expression levels were significantly reduced in human CSCC tissues and cells compared with normal samples. Overexpression of FABP7 inhibited the proliferation, invasion and migration abilities of A431 and colo-16 cells compared with those in the negative control group. In addition, transfection with oeFABP7 reduced the expression levels of proliferation-, invasion- and Notch pathway-associated proteins compared with those in the negative control group. Overexpression of FABP7 also reduced the growth of CSCC tumors

The rise of antimicrobial resistance has created an urgent need for antibiotic-alternative strategies for disease control and prevention. Host defense peptides (HDPs), which have both antimicrobial and immunomodulatory properties, are an important component of the innate immune system. A host-directed approach to stimulate the synthesis of endogenous HDPs has emerged as a promising solution to treat infections with a minimum risk for developing antimicrobial resistance. Among a diverse group of compounds that have been identified as inducers of HDP synthesis are polyphenols, which are naturally occurring secondary metabolites of plants characterized by the presence of multiple phenol units. In addition to their well-known antioxidant and anti-inflammatory activities, a variety of polyphenols have been shown to stimulate HDP synthesis across animal species. This review summarizes both the in vitro and in vivo evidence of polyphenols regulating HDP synthesis. The mechanisms by which polyphenols induce HDP gene expression are also discussed. Natural polyphenols warrant further investigation as potential antibiotic alternatives for the control and prevention of infectious diseases.

Linear psoriasis is an unusual type of psoriasis that was first reported in 19511 . It is characterized by the linear distribution of psoriatic lesions along the lines of Blaschko. Linear psoriasis is easily confused with linear lichen planus and inflammatory linear verrucous epidermal nevus2 . Histopathology can provide an accurate basis for its diagnosis; however, the involvement of invasive methods can lead to trauma.

Uneven snow distribution plays a main role in the collapse of two-span single-pitched roofs because of the intensified snow accumulation in the valleys and eaves. The roof pitches, wind velocities, and wind directions are the main reasons that cause unbalanced snowdrifts as they drastically affect the flow fields around the roofs. This research investigates the snow distribution characteristics on two-span single-pitched roofs based on the snow-wind combined experiment facility and new similarity criteria. Firstly, the setup of the experiment facility is introduced, and the wind fans matrix and snowfall simulator are calibrated, respectively. Then, a new Froude number similarity, based on the modification of friction velocity ratio, is proposed, and its reliability as a criterion is verified. Finally, experiments on two-span single-pitched roofs are conducted using the new similarity criteria to study the snowdrifts patterns under different conditions. The mechanism of snow accumulations on roofs is explained with the help of CFD calculation. The results show that the valley and eave on the second windward roof bear a larger snow load.

Host defense peptides (HDPs) are an integral part of the innate immune system acting as the first line of defense. Modulation of HDP synthesis has emerged as a promising host-directed approach to fight against infections. Inhibition of histone deacetylation or DNA methylation is known to enhance HDP gene expression. In this study, we explored a possible synergy in HDP gene induction between histone deacetylase inhibitors (HDACi) and DNA/histone methyltransferase inhibitors (DNMTi/HMTi). Two chicken macrophage cell lines were treated with structurally distinct HDACi, HMTi, or DNMTi individually or in combinations, followed by HDP gene expression analysis. Each epigenetic compound was found to be capable of inducing HDP expression. To our surprise, a combination of HDACi and HMTi or HDACi and DNMTi showed a strong synergy to induce the expressions of most HDP genes. The HDP-inducing synergy between butyrate, an HDACi, and BIX01294, an HMTi, were further verified in chicken peripheral blood mononuclear cells. Furthermore, tight junction proteins such as claudin 1 were also synergistically induced by HDACi and HMTi. Overall, we conclude that HDP genes are regulated by epigenetic modifications. Strategies to increase histone acetylation while reducing DNA or histone methylation exert a synergistic effect on HDP induction and, therefore, have potential for the control and prevention of infectious diseases.

Immune checkpoint blockade (ICB) is a powerful oncologic treatment modality for a wide variety of human malignancies, but the patient response rate to this treatment remains low, especially in patients with cutaneous squamous cell carcinoma (cSCC). 5-Aminoleuvulinic acid-photodynamic therapy (ALA-PDT) is widely used to treat cancerous and precancerous skin diseases, but the value of ALA-PDT in the treatment of invasive cSCC is debatable. Our previous studies have shown that ALA-PDT can induce antitumor immune responses by promoting the immunogenic death of tumor cells. However, it is unclear whether ALA-PDT exerts synergistic effects with ICB in cSCC. Here, we report that PD-L1 blockade potentiates the antitumor effects of ALA-PDT both on primary and distant tumors, and optimizes the tumor microenvironment in cSCC. In this study, we first detected PD-L1 expression in patients with different grades of cSCC. Then we found the combination of anti-PD-L1 monoclonal antibody (mAb) and ALA-PDT killed tumor cells by apoptosis- and/or ferroptosis-mediated immunogenic cell death (ICD) and stimulated systemic immune response, as well as building the immunological memory response to prevent tumor recurrence. Furthermore, we found that combination therapy can be used to recruit tertiary lymphoid structure (TLS)-like intratumoral lymphoid aggregates, which may promote tumor-infiltrating lymphocyte (TIL)-mediated antitumor immunity. In summary, our work demonstrates that ICB treatment with an anti-PD-L1 antibody is a promising strategy that may potentiate the antitumor effects of ALA-PDT in cSCC.

Background Extensive work has been accomplished to characterize the intestinal bacterial community, known as the microbiota, and its association with host health and disease. However, very little is known about the spatiotemporal development and the origin of a minor intestinal fungal community, known as the mycobiota, in humans and animals, particularly in avian species. Results In this study, we comprehensively characterized the biogeography and succession of the gastrointestinal (GI) mycobiota of broiler chickens and further revealed the fungal sources that are responsible for initial and long-term establishment of the mycobiota in the GI tract. Using Illumina sequencing of the internal transcribed spacer 2 (ITS2) region of fungal rRNA genes, we detected significant spatial and temporal differences in the mycobiota along the GI tract. In contrary to the microbiota, the mycobiota was more diverse in the upper than the lower GI tract with no apparent trend of succession up to 42 days of age. The intestinal mycobiota was dominated by the phyla Ascomycota and Basidiomycota with Gibberella, Aspergillus, and Candida being the most abundant genera. Although the chicken mycobiota was highly dynamic, Fusarium pseudonygamai was dominant throughout the GI tract regardless of age in this study. The core chicken mycobiome consisted of 26 fungal taxa accounting for greater than 85% of the fungal population in each GI location. However, we observed high variations of the intestinal mycobiota among different studies. We also showed that the total fungal population varied greatly from 1.0 × 104 to 1.1 × 106 /g digesta along the GI tract and only accounted for less than 0.06% of the bacteria in day-42 broilers. Finally, we revealed that the mycobiota from the hatchery environment was responsible for initial colonization in the GI tract of newly hatched chickens, but was quickly replaced by the fungi in the diet within 3 days. Conclusions Relative to the intestinal microbiota that consists of trillions of bacteria in hundreds of different species and becomes relatively stabilized as animals age, the chicken intestinal mycobiota is a minor microbial community that is temporally dynamic with limited diversity and no obvious pattern of successive changes. However, similar to the microbiota, the chicken mycobiota is spatially different along the GI tract, although it is more diverse in the upper than the lower GI tract. Dietary fungi are the major source of the intestinal mycobiota in growing chickens.

BACKGROUND Laser therapies have brought dawn to refractory skin diseases, but also were accompanied by postlaser inflammation and skin barrier dysfunction. To recover skin function quickly, the research and development of active ingredients including β-glucan for postlaser repair have attracted much attention. AIMS To evaluate the efficacy and tolerance of skin care regimens containing β-glucan (Dermdoc®;Songyang Biotech) in repairing postlaser inflammation and skin barrier dysfunction after fractional laser therapy. METHODS A total of 20 patients with facial atrophic acne scars who accepted fractional laser therapy were recruited: 10 patients treated with ablative fractional CO2 laser and 10 patients treated with 1565nm nonablative fractional laser. Using the method of split-face vehicle-control study, the left half of the face was served as the treatment side and accepted skin care regimens, and the right half was control side accepted vehicle. Noninvasive bioinstrumentation of skin hydration index, transepidermal water loss (TEWL), and hemoglobin index (E value) was detected in the study. Standard digital photographs were taken at each visit. The skin tolerance and adverse effect were also evaluated by subject questionnaire. RESULTS Compared with the control side, the Hemoglobin index (E value) of the treatment side was improved more significantly on the 7th day (P

Fault is one of the common geological structures in coal mining, the concentrated development of several faults has changed the movement form and structure shape of overlying strata, which caused the instability of overburden strata easily and induced dynamic disasters. Taking the 10,416 working face of Yangliu coal mine as the research object, the plane numerical model of overburden structure with two faults (a reverse fault and a normal fault) was established by using UDEC numerical simulation software. The dip angle of normal fault is 50°, the dip angle of normal fault is 70°. The distances between the two faults are 30 m, 60 m, 90 m. The evolution characteristics of overburden structure in working face are studied respectively from hanging wall to footwall and from footwall to hanging wall, and the dynamic hazard law induced by the activation of different faults is analyzed. The results prove that: when the working face is mined from footwall to hanging wall, the overlying strata on the working surface form “trapezoid” and “triangle” structures. When the working face is mined from hanging wall to footwall, the overlying strata form the structure of “inverted trapezoid” and “inverted triangle”. The low-level fault activation caused by overburden movement is easy to induce dynamic response. Finally, the research results are verified by using the microseismic activity of 10,416 working face in Yangliu coal mine.

Desertification is the impoverishment of arid, semiarid, and some subhumid ecosystems. The assessment of global scale desertification vulnerability to climate change and human activity is important to help decision makers formulate the best strategies for land rehabilitation and combat global desertification in sensitive areas. There is no global desertification vulnerability map that considers both climate change and human activities. The main aim of this study was to construct a new index, the global desertification vulnerability index (GDVI), by combining climate change and human activity, provide another perspective on desertification vulnerability on a global scale, and project its future evolution. Using the probability density function of the GDVI, we classified desertification vulnerability into four classes: very high, high, medium, and low. The results of the analysis indicated that areas around deserts and barren land have a higher risk of desertification. Areas with a moderate, high, and very high desertification risk accounted for 13%, 7%, and 9% of the global area, respectively. Among the representative concentration pathways (RCPs), RCP8.5 projected that the area of moderate to very high desertification risk will increase by 23% by the end of this century. The areas where desertification risks are predicted to increase over time are mainly in Africa, North America, and the northern areas of China and India.

The aims of this study were to examine the symptom severity and interference among patients with lung cancer treated with PD-1 immunotherapy, explore whether those symptoms were clustered together, and identify factors associated with symptom clusters.A cross-sectional study was conducted. Data were collected by demographic and clinical characteristic questionnaires and the M.D. Anderson Symptom Inventory Lung Cancer Module. Symptom clusters were identified using exploratory factor analysis, and stepwise linear regression was applied to analyze the factors affecting the symptom clusters.A total of 148 patients with lung cancer treated with PD-1 immunotherapy participated in this study. The overall symptom burdens of these patients were mainly at a mild level. The patient symptom clusters identified in this study were a general cluster, a treatment-related cluster, a pulmonary cluster, a gastrointestinal cluster, and a neural cluster. The patients' Karnofsky performance status (KPS) score (The symptom burdens of patients with lung cancer and treated with PD-1 immunotherapy were at a mild level and appeared to be clustered. In addition, because the symptoms that comprise a cluster are interrelated, the diagnosis and management of each symptom in a cluster should not be performed in isolation, and each symptom in a cluster should be treated either simultaneously or in an orderly manner.

Enhancing the synthesis of microbicidal and immunomodulatory host defense peptides (HDP) is a promising host-directed antimicrobial strategy to combat a growing threat of antimicrobial resistance. Here we investigated the effect of several natural cyclooxygenase-2 (COX-2) inhibitors on chicken HDP gene regulation. Our results indicated that phenolic COX-2 inhibitors such as quercetin, resveratrol, epigallocatechin gallate, anacardic acid, and garcinol enhanced HDP gene expression in chicken HTC macrophage cell line and peripheral blood mononuclear cells (PBMCs). Moreover, these natural COX-2 inhibitors showed a strong synergy with butyrate in augmenting the expressions of multiple HDP genes in HTC cells and PBMCs. Additionally, quercetin and butyrate synergistically promoted the expressions of mucin-2 and claudin-1, two major genes involved in barrier function, while suppressing lipopolysaccharide-triggered interleukin-1β expression in HTC macrophages. Mechanistically, we revealed that NF-κB, p38 mitogen-activated protein kinase, and cyclic adenosine monophosphate signaling pathways were all involved in the avian β-defensin 9 gene induction, but histone H4 was not hyperacetylated in response to a combination of butyrate and quercetin. Because of their HDP-inducing, barrier-protective, and antiinflammatory activities, these natural COX-2 inhibitors, when combined with butyrate, may be developed as novel host-directed antimicrobial therapeutics.

Severe acne vulgaris is a common chronic inflammatory skin disease worldwide. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is effective and safe for severe acne. However, the mechanism is not fully understood. Intense acute inflammatory response at 24 h after ALA-PDT is reported positively correlated to the effectiveness. Inflammation regulation influence the progression or outcome of diseases. ALA-PDT may exert its therapeutic effect by augmenting intense inflammation and break the chronic inflammation. This study was set out to explore the mechanism of ALA-PDT augmenting intense acute inflammation in the treatment of acne. As a result, transcriptome microarrays analysis of severe acne patients showed that ALA-PDT significantly up-regulated expression of various inflammation-related genes, especially TREM1 and PTGS2, which were further confirmed by a C.acnes induced acne-like mouse ear model. The subsequent experiments demonstrated that ALA-PDT could trigger pro-inflammatory M1 polarization of macrophages in vitro and in vivo. Additionally, the crosstalk between keratinocytes and macrophages studied by a transwell co-culture system indicated that PGE2 secreted by ALA-PDT treated HaCaT cells could promote THP-1 macrophages M1 polarization by COX2/PGE2/TLR4/TREM1 axis to augment inflammation. Our study provides a novel insight that ALA-PDT could amplify inflammation by COX2/TREM1 mediated macrophages M1 polarization for the treatment of acne. It is hoped that this research will decipher the mechanism of ALA-PDT for the treatment of acne and provide a theoretical basis for optimizing the clinical ALA-PDT management.