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Abstract Background Pangolins are the only mammals that have overlapping scales covering most of their bodies, and they play a crucial role in the ecosystem, biological research, and human health and disease. Previous studies indicated pangolin scale might provide an important mechanical defense to themselves. The origin and exact functions of this unique trait remain a mystery. Using a multi-omics analysis approach, we report a novel functional explanation for how mammalian scales can provide host–pathogen defense. Results Our data suggest that pangolin scales have a sophisticated structure that could potentially trap pathogens. We identified numerous proteins and metabolites exhibiting antimicrobial activity, which could suggest a role for scales in pathogen defense. Notably, we found evidence suggesting the presence of exosomes derived from diverse cellular origins, including mesenchymal stem cells, immune cells, and keratinocytes. This observation suggests a complex interplay where various cell types may contribute to the release of exosomes and antimicrobial compounds at the interface between scales and viable tissue. These findings indicate that pangolin scales may serve as a multifaceted defense system, potentially contributing to innate immunity. Comparisons with human nail and hair revealed pangolin-specific proteins that were enriched in functions relating to sensing, immune responses, neutrophil degranulation, and stress responses. We demonstrated the antimicrobial activity of key pangolin scale components on pathogenic bacteria by antimicrobial assays. Conclusions This study identifies a potential role of pangolin scales and implicates scales, as possible determinants of pathogen defense due to their structure and contents. We indicate for the first time the presence of exosomes in pangolin scales and propose the new functions of scales and their mechanisms. This new mechanism could have implications for multiple fields, including providing interesting new research directions and important insights that can be useful for synthesizing and implementing new biomimetic antimicrobial approaches.

Left atrial dissection (LatD) is a very rare complication of cardiac surgery, but it is relatively more common in mitral valve surgery. Transesophageal echocardiography (TEE) plays an important role in timely detection of LatD and accurate assessment of the condition, which are key factors in determining the patient's prognosis. There are two different treatment options for patients with or without circulatory crisis caused by dissection hematoma, namely surgical management and conservative treatment. In this report, we used TEE to quickly detect the cause and severity of LatD, which assisted the surgeon in making appropriate surgical decisions. The patient was successfully surgically treated for LatD.

Lychee, a key economic crop in southern China, has numerous similar-looking varieties. Classifying these can aid farmers in understanding each variety's growth and market demand, enhancing agricultural efficiency. However, existing classification techniques are subjective, complex, and costly. This paper proposes a lychee classification method using an improved ResNet-34 residual network for six common varieties. We enhance the CBAM attention mechanism by replacing the large receptive field in the SAM module with a smaller one. Attention mechanisms are added at key network stages, focusing on crucial image information. Transfer learning is employed to apply ImageNet-trained model weights to this task. Test set evaluations demonstrate that our improved ResNet-34 network surpasses the original, achieving a recognition accuracy of 95.8442%, a 5.58 percentage point improvement.

Abstract Protection of the Critically Endangered East Asian Pangolin species is hampered by the vulnerability of captive individuals to infection. Studies have previously shown the pangolin to have a unique pseudogenisation of many immunity genes (including IFNE, IFIH1, cGAS, STING, TLR5, and TLR11), and we suspected that these losses could account for this vulnerability. Here we used RNA-Seq data to show the effect of these gene losses on the transcriptional response to a viral skin infection in a deceased pangolin. This virus is very closely related to the one causing the current COVID-19 pandemic in the human population (SARS-CoV2), and we found the most upregulated pathway was the same one previously identified in the lungs of SARS-CoV2-infected humans. As predicted, we found that the pathways downstream of the lost genes were not upregulated. For example, the pseudogenised interferon epsilon (IFNE) is known to be particularly important in epithelial immunity, and we show that interferon-related responses were not upregulated in the infected pangolin skin. We suggest that the pangolin’s innate gene pseudogenisation is indeed likely to be responsible for the animal’s vulnerability to infection.

AbstractBackgroundThyroid hormone receptor interacting protein 13 (Trip13) is an AAA‐ATPase that regulates the assembly or disassembly protein complexes and mediates Double‐strand breaks (DSBs) repair. Overexpression of Trip13 has been detected in many cancers and is associated with myeloma progression, disease relapse and poor prognosis inmultiple myeloma (MM).MethodsWe have identified a small molecular, TI17, through a parallel compound‐centric approach, which specifically targets Trip13. To identify whether TI17 targeted Trip13, pull‐down and nuclear magnetic resonance spectroscopy (NMR) assays were performed. Cell counting kit‐8, clone formation, apoptosis and cell cycle assays were applied to investigate the effects of TI17. We also utilized a mouse model to investigate the effects of TI17 in vivo. ResultsTI17 effectively inhibited the proliferation of MM cells, and induced the cycle arrest and apoptosis of MM cells. Furthermore, treatment with TI17 abrogates tumor growth and has no apparent side effects in mouse xenograft models. TI17 specifically impaired Trip13 function of DSBs repair and enhanced DNA damage responses in MM. Combining with melphalan or HDAC inhibitor panobinostat triggers synergistic anti‐MM effect. ConclusionsOur study suggests that TI17 could be acted as a specific inhibitor of Trip13 and supports a preclinical proof of concept for therapeutic targeting of Trip13 in MM.

Abstract Supramolecular chirality‐mediated selective interaction among native assemblies is essential for precise disease diagnosis and treatment. Herein, to fully understand the supramolecular chiral binding affinity‐achieved therapeutic efficiency, supramolecular chiral nanoparticles (WP5⊃D/L‐Arg+DOX+ICG) with the chirality transfer from chiral arginine (D/L‐Arg) to water‐soluble pillar[5]arene (WP5) are developed through non‐covalent interactions, in which an anticancer drug (DOX, doxorubicin hydrochloride) and a photothermal agent (ICG, indocyanine green) are successfully loaded. Interestingly, the WP5⊃D‐Arg nanoparticles show 107 folds stronger binding capability toward phospholipid‐composed liposomes compared with WP5⊃L‐Arg. The enantioselective interaction further triggers the supramolecular chirality‐specific drug accumulation in cancer cells. As a consequence, WP5⊃D‐Arg+DOX+ICG exhibits extremely enhanced chemo‐photothermal synergistic therapeutic efficacy (tumor inhibition rate of 99.4%) than that of WP5⊃L‐Arg+DOX+ICG (tumor inhibition rate of 56.4%) under the same condition. This work reveals the breakthrough that supramolecular chiral assemblies can induce surprisingly large difference in cancer therapy, providing strong support for the significance of supramolecular chirality in bio‐application.

Abstract Background Multiple myeloma (MM), an incurable disease owing to drug resistance, requires safe and effective therapies. Norcantharidin (NCTD), an active ingredient in traditional Chinese medicines, possesses activity against different cancers. However, its toxicity and narrow treatment window limit its clinical application. In this study, we synthesized a series of derivatives of NCTD to address this. Among these compounds, DCZ5417 demonstrated the greatest anti-MM effect and fewest side effects. Its anti-myeloma effects and the mechanism were further tested. Methods Molecular docking, pull-down, surface plasmon resonance-binding, cellular thermal shift, and ATPase assays were used to study the targets of DCZ5417. Bioinformatic, genetic, and pharmacological approaches were used to elucidate the mechanisms associated with DCZ5417 activity. Results We confirmed a highly potent interaction between DCZ5417 and TRIP13. DCZ5417 inhibited the ATPase activity of TRIP13, and its anti-MM activity was found to depend on TRIP13. A mechanistic study verified that DCZ5417 suppressed cell proliferation by targeting TRIP13, disturbing the TRIP13/YWHAE complex and inhibiting the ERK/MAPK signaling axis. DCZ5417 also showed a combined lethal effect with traditional anti-MM drugs. Furthermore, the tumor growth-inhibitory effect of DCZ5417 was demonstrated using in vivo tumor xenograft models. Conclusions DCZ5417 suppresses MM progression in vitro, in vivo, and in primary cells from drug-resistant patients, affecting cell proliferation by targeting TRIP13, destroying the TRIP13/YWHAE complex, and inhibiting ERK/MAPK signaling. These results imply a new and effective therapeutic strategy for MM treatment.

Abstract Chemokines secreted by dendritic cells (DCs) play a key role in the regulation of inflammation and autoimmunity through chemokine receptors. However, the role of chemokine receptor CXCR1 in inflammation-inducing experimental autoimmune encephalomyelitis (EAE) and acute respiratory distress syndrome (ARDS) remains largely enigmatic. Here we reported that compared with healthy controls, the level of CXCR1 was aberrantly increased in multiple sclerosis (MS) patients. Knockout of CXCR1 not only ameliorated disease severity in EAE mice but also suppressed the secretion of inflammatory factors (IL-6/IL-12p70) production. We observed the same results in EAE mice with DCs-specific deletion of CXCR1 and antibody neutralization of the ligand CXCL5. Mechanically, we demonstrated a positive feedback loop composed of CXCL5/CXCR1/HIF-1α direct regulating of IL-6/IL-12p70 production in DCs. Meanwhile, we found CXCR1 deficiency in DCs limited IL-6/IL-12p70 production and lung injury in LPS-induced ARDS, a disease model caused by inflammation. Overall, our study reveals CXCR1 governs DCs-mediated inflammation and autoimmune disorders and its potential as a therapeutic target for related diseases.

This study uses machine learning to identify critical factors influencing the cost-effectiveness of over-the-counter (OTC) medications. By developing a novel cost-effectiveness rating (CER) based on user ratings and prices, we analyzed data from Amazon. The findings indicate that Flexible Spending Account (FSA)/Health Savings Account (HSA) eligibility, symptom treatment range, safety warnings, special effects, active ingredients, and packaging size significantly impact cost-effectiveness across cold, allergy, digestion, and pain relief medications. Medications eligible for FSA or HSA funds, treating a broader range of symptoms, and having smaller packaging are perceived as more cost-effective. Cold medicines with safety warnings were cost-effective due to their lower average price and effective ingredients like phenylephrine and acetaminophen. Allergy medications with kid-friendly features showed higher cost-effectiveness, and ingredients like calcium, famotidine, and magnesium boosted the cost-effectiveness of digestion medicines. These insights help consumers make informed purchasing decisions and assist manufacturers and retailers in enhancing product competitiveness. Overall, this research supports better decision-making in the pharmaceutical industry by highlighting factors that drive cost-effective medication purchases.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious disease that affects 30 % of the global population and poses a significant risk to human health. However, to date, no safe, effective and appropriate treatment modalities are available. In recent years, ferroptosis has emerged as a significant mode of cell death and has been found to play a key regulatory role in the development of NAFLD. In this study, we found that arbutin (ARB), a natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits the onset of ferroptosis and ameliorates high-fat diet-induced NAFLD in vivo and in vitro. Using reverse docking, we identified the demethylase fat mass and obesity-related protein (FTO) as a potential target of ARB. Subsequent mechanistic studies revealed that ARB plays a role in controlling methylation of the SLC7A11 gene through inhibition of FTO. In addition, we demonstrated that SLC7A11 could alleviate the development of NAFLD in vivo and in vitro. Our findings identify the FTO/SLC7A11 axis as a potential therapeutic target for the treatment of NAFLD. Specifically, we show that ARB alleviates NAFLD by acting on the FTO/SLC7A11 pathway to inhibit ferroptosis.

In this work, a recyclable and sensitive fluorescent nanoprobe, RhoB@ZIF-8 composite, has been designed and successfully synthesized by encapsulating rhodamine B (abbreviated as RhoB) into the cavities of zeolitic imidazolate framework-8 (ZIF-8) metal-organic frameworks (MOFs) through a facile one-pot method under mild conditions. The RhoB@ZIF-8 composite exhibited an emission band at 589 nm with fluorescent quantum yield of 19.8%. Since there was an efficient overlap between the absorption of malachite green (MG) and the fluorescence spectra (excitation and emission bands) of RhoB@ZIF-8 composite, the fluorescence intensity decreased sharply after MG was added. The fluorescence quenching was linear with the concentration of MG in the range of 0 to 13.0 μM with a low limit of detection (LOD) of 0.089 μM. Remarkably, this proposed sensing system has good performances including high specificity, good stability and recyclability. Finally, this fluorescent probe was successfully applied to the detection of MG in aquaculture water and fish tissue samples, revealing its potential practicability. This work will provide us a new research platform for MG sensing.

Abstract Protecting and restoring the degraded arid lakes are globally urgent issues. We document a potential recovery of the dried salt-lake, Lop Nur called "the Sea of Death" which is located at the terminus of the largest inland basin in China, the Tarim River Basin. The changes and relationship of surface water with climate parameters and groundwater in the basin over the last 30 years are analyzed, by using satellite remote sensing and land data assimilation products. We find that with increased surface water in the basin, the groundwater level in Lop Nur began to show an obvious positive response in 2015; and the rate of decline of the groundwater level is slowing down. We argue that after a balance is achieved between regional groundwater recharge and evapotranspiration, the Lop Nur ecosystem will gradually recover. This study shows an encouraging case for the protection and restoration of degraded lakes in dryland regions around the world.

Wildlife trafficking poses a major threat to global biodiversity. Species such as pangolins are particularly vulnerable and trade continues almost unabated despite numerous interventions aimed at eradicating illegal wildlife trade. Despite restrictions on the pangolin trade, thousands of pangolins continue to be intercepted annually. We focused on China because of the recent delisting of pangolins from the Chinese pharmacopeia, and their removal from healthcare insurance, despite deeply ingrained traditions of having pangolins for ethno-medicinal use. We collated pangolin interception data from public online media seizure reports to characterize the pangolin trade within China, and found that a total of 326 independent seizures equivalent to 143,130 pangolins (31,676 individuals and 222,908 kg of scale) were reported in 26 provinces. Pangolin domestic seizures are greatest in the southern cities of Dehong, Fangchenggang, and Guangzhou. Also, we found 17 countries within the global pangolins range which were the major source of the pangolin shipments to China. The number of arrests and convictions was much lower than the number of pangolin incidents reported. Our results show a significant increase in the volume of scales and number of live pangolin seizures after amended endangered species law came into effect in 2018, and recorded the highest number of individual pangolin interceptions. China has shown increasing wildlife seizures over time, owing partly to emergent trends in the international wildlife trade as well as increasing global demand for ethnomedicine. The future eradication of illegal wildlife trade in China is dependent not only on stringent border control and offender prosecution but also the; removal of other threatened species from the pharmacopeia and healthcare insurance which includes wildlife derivatives. Furthermore, our work highlights importance of current policy intervention to combat the pangolin trade within China, and the need for further interventions both within China and in export countries.

Sentiment analysis (SA) is an important task in natural language processing in which convolutional neural networks (CNNs) have been successfully applied. However, most existing CNNs can only extract predefined, fixed-scale sentiment features and cannot synthesize flexible, multi-scale sentiment features. Moreover, these models’ convolutional and pooling layers gradually lose local detailed information. In this study, a new CNN model based on residual network technology and attention mechanisms is proposed. This model exploits more abundant multi-scale sentiment features and addresses the loss of locally detailed information to enhance the accuracy of sentiment classification. It is primarily composed of a position-wise gated Res2Net (PG-Res2Net) module and a selective fusing module. The PG-Res2Net module can adaptively learn multi-scale sentiment features over a large range using multi-way convolution, residual-like connections, and position-wise gates. The selective fusing module is developed to fully reuse and selectively fuse these features for prediction. The proposed model was evaluated using five baseline datasets. The experimental results demonstrate that the proposed model surpassed the other models in performance. In the best case, the model outperforms the other models by up to 1.2%. Ablation studies and visualizations further revealed the model’s ability to extract and fuse multi-scale sentiment features.

IntroductionProtecting the supraclavicular nerve during internal fixation of clavicular fractures can reduce numbness in its innervation area after surgery. Previous methods for supraclavicular nerve protection are empirical, time-consuming, and approximate. In this report, we verified the feasibility of using ultrasound for percutaneous localization of the terminal branches of the supraclavicular nerve and the feasibility of an ultrasound-guided skin flap reserve technique for nerve protection.Case PresentationsA high-frequency linear array probe was used in three cases to trace the supraclavicular nerve from its origin at the superficial cervical plexus on the surface of the clavicle. In the first case, the feasibility of percutaneous ultrasound localization of the terminal branches of the supraclavicular nerve was determined by performing an ultrasound-guided nerve block. In the second case, the feasibility of this method was determined by directly isolating this nerve under direct vision. In the third case, after the ultrasound localization, the nerves were protected by intraoperative skin retention. In the first case, skin anesthesia of the innervation area of the intermediate branch of the supraclavicular nerve was achieved. In the second case, the part of the nerve that crosses the surface of the clavicle was quickly found and successfully protected, and no obvious abnormal skin sensations were noted after the operation. In the third case, there was no abnormal sensation in most of the associated skin except for the innervation area of the lateral branch of the supraclavicular nerve.ConclusionsThe medial and intermediate branches of the supraclavicular nerve could be located over the skin by ultrasound, and this could be helpful in quickly isolating these nerves intraoperatively. Retaining the corresponding skin can protect the function of these nerve branches and effectively reduce the area of skin numbness after surgery.

Abstract Background Sun’s procedure is currently recognized as the standard procedure for acute type A aortic dissection (AAAD). But the operation istoo difficult for beginners. We hope to reduce the difficulty and complications of this operation. Methods The aortic arch was immediately cross-clamped after the stented graft was inserted into the distal aorta. Thereafter, the lower-body perfusion was restored. Then, anastomosis was performed between the proximal stent graft and the distal 4-branched Dacron graft. The other arteries were anastomosed to the arched branch of the 4-branched graft. Results The cardiopulmonary bypass (CPB) time was (207 ± 52) min, and the aortic cross-clamp time was (114 ± 39) min. The circulatory arrest time was (38 ± 16) sec. One patient (4%) died. The incidence of complications was stroke (4%), renal dysfunction requiring dialysis (4%), prolonged intubation(12%). Conclusions The time of circulatory arrest in this operation is less than 1 min, which can avoid the complications caused by DHCA and decrease risk of bleeding and complexity by shifting anastomosis more proximally. The effect of our operation is similar to and even better than that of Sun’s procedure. It does not even require relatively advanced skill, much experience and excellent psychological quality, especially suitable for beginners.

Abstract Background DCZ3301, a novel aryl-guanidino compound previously reported by our group, exerts cytotoxic effects against multiple myeloma (MM), diffused large B cell lymphoma (DLBCL), and T-cell leukemia/lymphoma. However, the underlying mechanism of its action remains unknown. Methods We generated bortezomib (BTZ)-resistant cell lines, treated them with various concentrations of DCZ3301 over varying periods, and studied its effect on colony formation, cell proliferation, apoptosis, cell cycle, DNA synthesis, and DNA damage response. We validated our results using in vitro and in vivo experimental models. Results DCZ3301 overcame bortezomib (BTZ) resistance through regulation of the G2/M checkpoint in multiple myeloma (MM) in vitro and in vivo. Furthermore, treatment of BTZ-resistant cells with DCZ3301 restored their drug sensitivity. DCZ3301 induced M phase cell cycle arrest in MM mainly via inhibiting DNA repair and enhancing DNA damage. Moreover, DCZ3301 promoted the phosphorylation of ATM, ATR, and their downstream proteins, and these responses were blocked by the ATM specific inhibitor KU55933. Conclusions Our study provides a proof-of-concept that warrants the clinical evaluation of DCZ3301 as a novel anti-tumor compound against BTZ resistance in MM.

Abstract Objective Aortic arch replacement in acute type A aortic dissection patients remains the most challenging cardiovascular operation. Herein, we described our modified Y-graft technique using the Femoral Artery Bypass (FAB) and the One Minute Systemic Circulatory Arrest (OSCA) technique, and assessed the short-term outcomes of the patients. Methods Between February 2015 and November 2017, 51 patients with acute type A aortic dissection underwent aortic arch replacement. Among them, 23 patients underwent FAB while 28 patients underwent both FAB and OSCA. The intraoperative data and postoperative follow-up data were recorded. The follow-up data of patients with traditional Y-graft technique were collected from previously reported studies. Results In the FAB group, two patients died due to pulmonary infection (30-day survival rate, 91.3%), and two patients were paralyzed from the waist down. Hemodialysis was performed for five patients (21.7%) before hospital discharge. Fifteen patients (65.2%) received respiratory support for more than 2-days and eight patients (34.8%) for more than 5-days. These follow-up results were comparable or better than the patients with traditional Y-graft technique. Furthermore, compared to the FAB group, the morbidity due to neurological dysfunction and acute renal failure was significantly reduced in the FAB+OSCA group. Moreover, the respiratory support, length of postoperative stay and ICU stay were shortened. Conclusions This study clarified the feasibility of FAB and OSCA technique in modifying Y-graft technique. The acute type A aortic dissection patients showed less surgical complications and favorable short-term outcomes after this surgery.

Abstract Background Despite expansion in the 2006 Sydney antiphospholipid syndrome (APS) classification criteria to include IgG/IgM anti-β2-glycoprotein (aβ2GPI) antibodies in addition to IgG/IgM anti-cardiolipin antibodies (aCL) and lupus anticoagulant (LAC), some individuals with clinical features of APS remain seronegative (seronegative APS or SNAPS) and are at risk of recurrent thrombosis and pregnancy morbidities. Our aim was to assess the value of “non-criteria” aPL antibodies to detect these SNAPS patients. Methods One hundred ninety-two APS patients, 90 SNAPS patients, 193 autoimmune disease controls, and 120 healthy controls were evaluated. Ten antiphospholipid antibodies (aPLs) were tested using commercial kits, including 5 non-criteria aPLs: anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, aCL IgA, aβ2GPI IgA, and anti-β2GPI Domain 1 (aβ2GPI-D1) IgG. Results Up to 60.9% of the SNAPS and 93.5% of APS patients were detected by at least one non-criteria aPL. aPS/PT IgG had the highest Youden index in classifying APS and SNAPS from controls. aPS/PT IgG and aβ2GPI Domain 1 IgG seem to be the most significant risk factors for thrombotic events and pregnancy morbidity, respectively. aPS/PT IgG/IgM and aβ2GPI-D1 IgG were detected in some SNAPS patients, while IgA isotypes of aCL/aβ2GPI tended to appear together with other biomarkers. The combined analysis showed enhanced diagnostic performance with the inclusion of non-criteria aPLs. Conclusions Recognition of SNAPS patients is critical for clinical management and prevention of potential thrombotic and obstetric adverse events. The non-criteria antiphospholipid antibodies help to identify a considerable portion (60.9%) of these patients who otherwise may remain untreated and at clinical risk.

This research aims to analyze the influencing factors of migrant children’s education integration based on the convolutional neural network (CNN) algorithm. The attention mechanism, LSTM, and GRU are introduced based on the CNN algorithm, to establish an ALGCNN model for text classification. Film and television review data set (MR), Stanford sentiment data set (SST), and news opinion data set (MPQA) are used to analyze the classification accuracy, loss value, Hamming loss (HL), precision (Pre), recall (Re), and micro-F1 (F1) of the ALGCNN model. Then, on the big data platform, data in the Comprehensive Management System of Floating Population and Rental Housing, Student Status Information Management System, and Student Information Management System of Beijing city are taken as samples. The ALGCNN model is used to classify and compare related data. It is found that in the MR, STT, and MPQA data sets, the classification accuracy and loss value of the ALGCNN model are better than other algorithms. HL is the lowest (15.2 ± 1.38%), the Pre is second only to the BERT algorithm, and the Re and F1 are both higher than other algorithms. From 2015 to 2019, the number of migrant children in different grades of elementary school shows a gradual increase. Among migrant children, the number of migrant children from other counties in this province is evidently higher than the number of migrant children from other provinces. Among children of migrant workers, the number of immigrants from other counties in this province is also notably higher than the number of immigrants from other provinces. With the gradual increase in the years, the proportion of township-level expenses shows a gradual decrease, whereas the proportion of district and county-level expenses shows a gradual increase. Moreover, the accuracy of the ALGCNN model in migrant children and local children data classification is 98.6 and 98.9%, respectively. The proportion of migrant children in the first and second grades of a primary school in Beijing city is obviously higher than that of local children (p < 0.05). The average final score of local children was greatly higher than that of migrant children (p < 0.05), whereas the scores of migrant children’s listening methods, learning skills, and learning environment adaptability are lower, which shows that an effective text classification model (ALGCNN) is established based on the CNN algorithm. In short, the children’s education costs, listening methods, learning skills, and learning environment adaptability are the main factors affecting migrant children’s educational integration, and this work provides a reference for the analysis of migrant children’s educational integration.

After the iconic outburst of Zonag Lake in Hoh Xil of Tibetan Plateau (TP) in 2011, the causes of the collapse and its impact on the volume of water contained by the downstream lakes have highly been concerned, but the overall changes of the hydrological ecosystem and its impacts on the basin are yet not clear. This paper analyzes the hydrological system (lake area and hydrological connection) and ecosystem (sandstorm activity and vegetation growth status) changes and their impacts on the regional ecological environment after the outburst event, based on remotely sensed images from 2000 to 2020, meteorological observations, and field surveys. The results show that the outburst of Zonag Lake has not only changed the regional hydrology and ecosystem pattern but also caused a trend of degradation in the ecological environment of Zonag Lake Basin. Some lambing areas and active areas of Tibetan antelope in the area are being buried and eroded by the sandstorm. The downstream Yanhu Lake has risen to the highest level and overflowed through the emergency diversion engineering. These impacts are continuously threatening the health of the ecological environment of the world natural heritage site in Hoh Xil, the safety of Qinghai-Tibet highway, Qinghai-Tibet railway, and other engineering facilities, as well as the stability of fluvial geomorphology in the northern most sources of Yangtze River.

Highland barley (Hordeum vulgare L. HB) has been demonstrated to have a series of dietotherapy values, including being low fat, low sugar, high fiber, and especially high in β-glucan. Long-term consumption could reduce the incidence of chronic diseases and metabolic syndromes. In this study, the regulating effect of modified highland barley (MHB) products, namely microwave fluidized HB, extruded and puffed HB, and ultrafine pulverized HB on lipid metabolism and liver injury in mice fed a high fat and cholesterol diet (HFCD) was investigated using microbiota diversity gene sequencing and untargeted metabolomics. A total of six groups of mice were supplemented with a normal diet or an HFCD, with or without MHB, and the experimental period lasted 10 weeks. The obtained results demonstrated that MHB supplementation could effectively reverse the increase in body weight gain and adipose tissue accumulation caused by an HFCD (p < 0.05). Moreover, serum biochemical parameters showed that MHB supplementation significantly decreased total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, while increasing high-density lipoprotein cholesterol (HDL-C) levels. The results of hematoxylin and eosin (H&E) assays showed that MHB supplementation could significantly improve the liver injury and adipose tissue accumulation. In addition, 16S rRNA amplicon sequencing showed that MHB supplementation increased the bacteroidetes/firmicutes ratio and the abundance Lactobacillus abundance, while also decreasing the Proteobacteria abundance, which are bacteria closely associated with the hyperlipidemia caused by HFCD. LC-MS metabolomics indicated that MHB supplementation significantly enhanced the levels of Deoxycholic acid, Myclobutanil, 3-Epiecdysone, 3,4-Dihydroxybenzeneacetic acid, and so on. In addition, MHB supplementation promoted activation of the Arachidonic acid metabolism pathways, the expression of ABC transporters, bile secretion, primary bile acid biosynthesis, and so on. Above all, this study showed the potential capacity of MHB to relieve hyperlipidemia and provides a reference for developing a new dietary intervention supplement to ameliorate hyperlipidemia.

Glutathione (GSH), as the most abundant low-molecular-weight biological thiol, plays significant roles in vivo. Abnormal GSH levels have been demonstrated to be related to the dysfunction of specific physiological activities and certain kinds of diseases. Therefore, the sensing of GSH is emerging as a critical issue. Cancer, with typical high morbidity and mortality, remains one of the most serious diseases to threaten public health. As it is clear that much more concentrated GSH is present at tumor sites than at normal sites, the in vivo sensing of GSH offers an option for the early diagnosis of cancer. Moreover, by monitoring the amounts of GSH in specific microenvironments, effective diagnosis of ROS levels, neurological diseases, or even stroke has been developed as well. In this review, we focus on the fluorescent methodologies for GSH detection, since they can be conveniently applied in living systems. First, the fluorescent sensing methods are introduced. Then, the principles for fluorescent sensing of GSH are discussed. In addition, the GSH-sensing-related biological applications are reviewed. Finally, the future opportunities in in the areas of fluorescent GSH sensing—in particular, fluorescent GSH-sensing-prompted disease diagnosis—are addressed.

Radical mastectomy is commonly performed under general anesthesia, and regional block is often used as assisted or postoperative analgesia. We herein report a case of successful radical mastectomy with severe aortic stenosis (SAS) by using ultrasound-guided regional anesthesia under sedation. A 66-year-old female with an American Society of Anesthesiology physical status IV; limited functional capacity with

Abstract Background Acetate, an economical industrial chemical, which is also the precursor of acetyl-CoA, could serve as an alternative substrate for biomanufacturing. This nontraditional substrate can be widely produced from syngas via hydrolysis or pyrolysis of the cellulosic biomass, chemical or microbial catalysis, anaerobic fermentation in treated wastewater, etc. However, the toxicity of acetate to microorganisms has held back its utilization, especially for the eukaryotes that are good hosts for production of complicated pharmaceuticals or chemicals. This study seeks to improve acetate utilization in a widely used yeast host, Komagataella phaffii (previously Pichia pastoris), by metabolic engineering of acetate tolerance, transport, and metabolism. Results A kinase-deficient library of K. phaffii was firstly used to screen acetate-resistant kinases. The HRK1 knockout strain was sensitive to acetate and overexpression of this gene improved acetate tolerance and cell growth of the strain. Also, overexpression of HRK1 caused a 55% productivity improvement of acetyl-CoA-dependent 6-methylsalicylic acid (6-MSA). However, activation of Hrk1 on membrane H(+)-ATPase Pma1 seemed not to work in the engineered strain. Acetate transporter gene ScFPS1* was further overexpressed, despite of not improving 6-MSA biosynthesis. To enhance acetate metabolism, acetyl-CoA synthesizing related genes, yeast PpACS1, ScACS1*, and E. coli ackA/pta were overexpressed separately. Introduction of PpACS1 and ScACS1* each increased biosynthesis of 6-MSA by approximately 20% on 20 mM acetate. Finally, co-overexpression of HRK1 and ScACS1* improved 6-MSA productivity by 51% on 20 mM acetate, despite that a low expression level of HRK1 happened when genes were expressed under the same promoter. Conclusions HRK1 screened by K. phaffii kinase-deficient library played an important role in acetate tolerance and was proved to profit the biosynthesis of acetyl-CoA-derived chemicals. It could be a potential target for metabolic engineering of acetate utilization in other eukaryotic hosts as well. A combined strategy of introducing genes for acetate tolerance and metabolism further improved biosynthesis of acetyl-CoA derived reporter compound in K. phaffii. This makes it a good choice for acetyl-CoA-derived chemicals with acetate as substrate or precursor in K. phaffii, which would also extend the use of this chassis host.

Abstract Background The asleep-awake-asleep (AAA) technique and laryngeal mask airway (LMA) is a common general anesthesia technique for deep brain stimulation (DBS) surgery. However, the LMA is not always the ideal artificial airway. In this report, we presented our experiences with nasotracheal intubation-extubation-intubation (IEI) and AAA techniques in DBS surgery for Parkinson’s disease (PD) patients to meet the needs of surgery and ensure patients’ safety and comfort. Case presentation Three PD patients scheduled for DBS surgery had to receive general anesthesia for various reasons. For the first asleep stage, general anesthesia and nasotracheal intubation was completed with routine methods. During the awake stage, we pulled the nasotracheal tube back right above the epiglottis under fiberoptic bronchoscope (FOB) guidance for microelectrode recording (MER), macrostimulation testing and verbal communication. Once monitoring is completed, we induced anesthesia with rapid sequence induction and utilized the FOB to advance the nasotracheal tube into the trachea again. To minimize airway irritations during the process, we sprayed the airway with lidocaine before any manipulation. The neurophysiologists completed neuromoinitroing successfully and all three patients were satisfied with the anesthesia provided at follow-up. Conclusion Nasotracheal IEI and AAA anesthetic techniques should be considered as a viable option during DBS surgery.

Abstract With changing climates globally, we see changes in not just average conditions, but also in extreme events, and such events require special attention due to their unpredictable yet significant impact on native biotas. One such event is the formation of a landscape scar at Zonag Lake caused by a climate change‐induced outburst flooding event that occurred on 15 September 2011. During the winter, the scar region became a new birthplace for sandstorms, and since the flooding, remote sensing monitoring shows that between 2011 and 2020, there were 285 sandstorm days (between November and March), relative to none prior. The outburst flooding event and consequential sandstorms threaten the key lambing area of the Tibetan antelope (Chiru), affect the water balance of the Zonag Lake and downstream lakes, and may even impact on the flow in the Yangtze River. Active human intervention may be needed to repair this new desert spit and reverse the slew of consequences which may otherwise lead to significant population declines in one of the major Chiru breeding grounds due to the progressive loss of vegetation productivity across their main breeding area.

Abstract Background Mitochondrial myopathies represent a group of disorders caused by mitochondrial defects that disrupt energy production. Most patients have issues from infancy to early childhood. Pregnancy in women with mitochondrial myopathy is uncommon and the management for these parturients is full of challenges. Case presentation A 36-year-old woman with mitochondrial myopathy was scheduled for caesarean section under a combined spinal-epidural anaesthesia and multi-model analgesia. The parturient was safe and the delivery was performed safely and smoothly, but there were some complications after surgery due to the complex condition of the patient. After consultation with and treatment from multiple disciplines, both the parturient and neonate were well and discharged. Conclusion It is important that patients with mitochondrial diseases are comprehensively assessed and monitored perioperatively.

An increasing body of evidence indicates that miR-149 can both suppress and promote tumor growth depending on the tumor type. However, the role of miR-149 in the progression of gastric cancer (GC) remains unknown. Here we report that miR-149 is a tumor suppressor in human gastric cancer. miR-149 expression is decreased in GC cell lines and clinical specimens in comparison to normal gastric epithelial cell and tissues, respectively. The expression levels of miR-149 also correlate with the differentiation degree of GC cells and tissues. Moreover, ectopic expression of miR-149 in gastric cancer cells inhibits proliferation and cell cycle progression by down-regulating ZBTB2, a potent repressor of the ARF-HDM2-p53-p21 pathway, with a potential binding site for miR-149 in its mRNA's 3'UTR. It is also found that ZBTB2 expression increases in GC cells and tissues compared to normal gastric epithelial cell and tissues, respectively. Silencing of ZBTB2 leads to suppression of cell growth and cell cycle arrest in G0/G1 phase, indicating that ZBTB2 may act as an oncogene in GC. Furthermore, transfection of miR-149 mimics into gastric cancer cells induces down-regulation of ZBTB2 and HDM2, and up-regulation of ARF, p53, and p21 compared to the controls. In summary, our data suggest that miR-149 functions as a tumor suppressor in human gastric cancer by, at least partially through, targeting ZBTB2.