The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Reservoir rock typing assessment in a coal-tight sand based heterogeneous geological formation through advanced AI methods.

Geoscientists now identify coal layers using conventional well logs. Coal layer identification is the main technical difficulty in coalbed methane exploration and development. This research uses advanced quantile-quantile plot, self-organizing maps (SOM), k-means clustering, t-distributed stochastic neighbor embedding (t-SNE) and qualitative log curve assessment through three wells (X4, X5, X6) in complex geological formation to distinguish coal from tight sand and shale. Also, we identify the reservoir rock typing (RRT), gas-bearing and non-gas bearing potential zones. Results showed gamma-ray and resistivity logs are not reliable tools for coal identification. Further, coal layers highlighted high acoustic (AC) and neutron porosity (CNL), low density (DEN), low photoelectric, and low porosity values as compared to tight sand and shale. While, tight sand highlighted 5-10% porosity values. The SOM and clustering assessment provided the evidence of good-quality RRT for tight sand facies, whereas other clusters related to shale and coal showed poor-quality RRT. A t-SNE algorithm accurately distinguished coal and was used to make CNL and DEN plot that showed the presence of low-rank bituminous coal rank in study area. The presented strategy through conventional logs shall provide help to comprehend coal-tight sand lithofacies units for future mining.

3α-Hydroxybufadienolides in Bufo gallbladders: structural insights and biotransformation.

Bufadienolides, naturally occurring steroids primarily found in toads, have garnered attention for their pharmacological properties and ecological significance. In this study, we isolated and identified 21 bufadienolides from the gallbladders of Bufo gargarizans, comprising four new compounds and 17 known ones. Notably, the predominance of 15 bufadienolides with a 3α-OH configuration in toad bile differs significantly from the 3ß-OH bufadienolides found in venom secreted by toad glands. Moreover, our investigation into the biotransformation of 3ß-OH and 3α-OH bufadienolides in the liver and kidney tissues of toads revealed an irreversible conversion from 3ß-OH to 3α-OH bufadienolides, suggesting a crucial role in toad self-detoxification. These findings provide valuable insights into the structural diversity of bufadienolides and advance our understanding of their medical and ecological significance.

Dual Branch Multi-Level Semantic Learning for Few-Shot Segmentation.

Few-shot semantic segmentation aims to segment novel-class objects in a query image with only a few annotated examples in support images. Although progress has been made recently by combining prototype-based metric learning, existing methods still face two main challenges. First, various intra-class objects between the support and query images or semantically similar inter-class objects can seriously harm the segmentation performance due to their poor feature representations. Second, the latent novel classes are treated as the background in most methods, leading to a learning bias, whereby these novel classes are difficult to correctly segment as foreground. To solve these problems, we propose a dual-branch learning method. The class-specific branch encourages representations of objects to be more distinguishable by increasing the inter-class distance while decreasing the intra-class distance. In parallel, the class-agnostic branch focuses on minimizing the foreground class feature distribution and maximizing the features between the foreground and background, thus increasing the generalizability to novel classes in the test stage. Furthermore, to obtain more representative features, pixel-level and prototype-level semantic learning are both involved in the two branches. The method is evaluated on PASCAL- 5i 1 -shot, PASCAL- 5i 5 -shot, COCO- 20i 1 -shot, and COCO- 20i 5 -shot, and extensive experiments show that our approach is effective for few-shot semantic segmentation despite its simplicity.

Summary of biological research on hepatoblastoma: a scoping review.

Background: Hepatoblastoma is the most prevalent primary hepatic malignancy in children, comprising 80% of pediatric hepatic malignancies and 1% of all pediatric malignancies. However, traditional treatments have proven inadequate in effectively curing hepatoblastoma, leading to a poor prognosis. Methods: A literature search was conducted on multiple electronic databases (PubMed and Google Scholar). A total of 86 articles were eligible for inclusion in this review. Result: This review aims to consolidate recent developments in hepatoblastoma research, focusing on the latest advances in cancer-associated genomics, epigenetic studies, transcriptional programs and molecular subtypes. We also discuss the current treatment approaches and forthcoming strategies to address cancer-associated biological challenges. Conclusion: To provide a comprehensive summary of the molecular mechanisms associated with hepatoblastoma occurrence, this review highlights three key aspects: genomics, epigenetics, and transcriptomics. Our review aims to facilitate the exploration of novel molecular mechanisms and the development of innovative clinical treatment strategies for hepatoblastoma.

Modified Glucose-insulin-potassium Therapy for Hemorrhage-induced Traumatic Cardiac Arrest in Rabbits.

OBJECTIVE: Resuscitation with whole blood is known to be better than that with saline in attaining the return of spontaneous circulation (ROSC) and improving the short-term survival rate for hemorrhage-induced traumatic cardiac arrest (HiTCA). However, the resuscitation with whole blood alone fails to address the pathophysiological abnormalities, including hyperglycemia, hyperkalemia and coagulopathy, after HiTCA. The present study aimed to determine whether the modified glucose-insulin-potassium (GIK) therapy can ameliorate the above-mentioned pathophysiological abnormalities, enhance the ROSC, improve the function of key organs, and reduce the mortality after HiTCA. METHODS: HiTCA was induced in rabbits (n=36) by controlled hemorrhage. Following arrest, the rabbits were randomly divided into three groups (n=12 each): group A (no resuscitation), group B (resuscitation with whole blood), and group C (resuscitation with whole blood plus GIK). The GIK therapy was administered based on the actual concentration of glucose and potassium. The ROSC rate and survival rate were obtained. Hemodynamical and biochemical changes were detected. Thromboelastography (TEG) was used to measure coagulation parameters, and enzyme-linked immunosorbent assay to detect parameters related to inflammation, coagulation and the function of brain. RESULTS: All animals in groups B and C attained ROSC. Two rabbits died 24-48 h after HiTCA in group B, while no rabbits died in group C. The GIK therapy significantly reduced the levels of blood glucose, potassium, and biological markers for inflammatory reaction, and improved the heart, kidney, liver and brain function in group C when compared to group B. Furthermore, the R values of TEG were significantly lower in group C than in group B, and the maximum amplitude of TEG was slightly lower in group B than in group C, with no significant difference found. CONCLUSION: Resuscitation with whole blood and modified GIK therapy combined can ameliorate the pathophysiological disorders, including hyperglycemia, hyperkalemia and coagulopathy, and may improve the function of key organs after HiTCA.

Opposite effects of Covid-19 infection on pitchers and batters: a retrospective study on Chinese Professional Baseball League players.

BACKGROUND: The influence of COVID-19 infection on elite athletes remains largely unknown, especially on baseball players. The goal of this study is to examine the actual performance of infected elite baseball players from the Chinese Professional Baseball League (CPBL) from a sabermetric point of view. METHODS: This was a retrospective observational cohort study. CPBL players who were infected with COVID-19 from April 27th to May 31st, 2022, were eligible for this study. The performance of study participants before and after COVID-19 infection was compared, and statistics from the batters and pitchers were analyzed separately. RESULTS: During the study interval, 56 players were infected with COVID-19, including 35 batters and 21 pitchers. After excluding injured players and players with inadequate playing opportunities, 23 batters and 12 pitchers were enrolled. For batters, there were no significant differences before and after COVID-19 infection. However, batters older than 28 years of age showed a decline in slugging percentage (0.372 vs. 0.292, P=0.049). Analysis of pitchers revealed significantly boosted fastball velocity after COVID-19 infection (142.10 km/h vs. 142.82 km/h, P=0.028) and improved strikeouts per nine innings (6.89 vs. 8.56, P=0.021). CONCLUSIONS: COVID-19 might have a potential influence on professional baseball players. For batters, veteran players more than 28 years of age were more likely to be negatively affected by COVID-19, whereas the effect of COVID-19 on pitchers was generally positive, with significantly improved fastball velocity and K/9 numbers.

Severe congenital neutropenia and liver abscess: Surgical treatment breaks the vicious cycle.

Here, we present a case with genetically confirmed SCN. The main symptom of the child was recurring fever. The combination of antibiotics combined with G-CSF injection was proved to be insufficient, and the patient developed "solid" liver abscess. After undergoing surgical anatomical hepatic lobectomy, the child's infection symptoms showed improvement. The postoperative culture of the purulent material from the liver infection lesion revealed an infection with Staphylococcus aureus. Our case raises the possibility of pathogen sources and routes of infection, clinical characteristics, and effective treatment for SCN patients with concomitant liver abscess.

Awake rabbit model of ischemic spinal cord injury with delayed paraplegia: The role of ambient temperature.

BACKGROUND: Paraplegia after spinal cord ischemia is a devastating condition in the clinic. Here, we develop an awake rabbit model of spinal cord ischemia with delayed paraplegia and explore the influence of ambient temperature on the outcomes after injury. METHODS: A total of 47 male rabbits were involved in the present study. Transient spinal cord ischemia was induced by occluding the infrarenal abdominal aorta of awake rabbits at different ambient temperatures. To find the optimal conditions for developing delayed paraplegia, hindlimb motor function after ischemia was evaluated between experiments. RESULTS: The onset and magnitude of ischemic injury varied with the ambient temperature maintained during the peri-ischemia period. More serious spinal cord injury occurred when ischemia was induced at higher temperatures. At 18°C, 25-minute ischemia resulted in 74% of rabbits developing delayed paraplegia. At a temperature of 28°C or higher, most of the animals developed acute paraplegia immediately. While at 13°C, rabbits usually regained normal motor function without paraplegia. CONCLUSION: This awake rabbit model is highly reproducible and will be helpful in future studies of delayed paraplegia after spinal cord ischemia. The ambient temperature must be considered while using this model during investigation of therapeutic interventions.

Characterization of a mouse-adapted strain of bat severe acute respiratory syndrome-related coronavirus.

Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.

Exploring the Catalytic Flexibility and Reversibility of Plant Glycosyltransferase HtUGT72AS1 for Glycodiversification of Phenolic Compounds.

Plant bioactive metabolites such as flavonoids are usually present in glycosylated forms by the attachment of various sugar groups. In this study, a catalytically flexible and reversible glycosyltransferase (HtUGT72AS1) was cloned and characterized from Helleborus thibetanus. HtUGT72AS1 could directly accept six sugar donors (UDP-glucose/-arabinose/-galactose/-xylose/-N-acetylglucosamine/-rhamnose) to catalyze the 3-OH glycosylation of flavonols. It also catalyzed the 4' and 7-OH glycosylation of other types of flavonoids, which lacked the 3-OH group. Additionally, the HtUGT72AS1-catalyzed reaction was highly reversible when using 2-chloro-4-nitrophenyl glycosides as substrates, which could be used for one-pot or coupled production of bioactive glycosides. It is the first reported UGT for the synthesis of arabinosides and galactosides using a transglycosylation platform. Based on structural modeling and mutagenetic analysis, the mutation of Tyr377 to Ara enhanced the catalytic efficiency of HtUGT72AS1 toward UDP-N-acetylglucosamine, and the V146S mutant gained an improvement in the regioselectivity toward 7-OH of flavonoids.

Discovery of anti-allergic components in Guomingkang Formula using sensitive HEMT biochips coupled with in vitro and in vivo validation.

BACKGROUND: Allergic rhinitis (AR) is a prevalent allergic disease, which seriously affects the sufferers' life quality and increases the socioeconomic burden. Guominkang (GMK), a well-known prescription for AR treatment, showed satisfactory effects; while its anti-allergic components remain to be disclosed. AlGaN/GaN HEMT biochip is more sensitive and cost-effective than other binding equipments, indicating its great potential for screening of active ingredients from herbal medicines. METHODS: AR mouse models were first established to test the anti-allergic effect of GMK and discover the ingredients absorbed into blood by ultra-high performance liquid chromatography-mass spectra (UHPLC-MS). Then, novel Syk/Lyn/Fyn-functionalized high electron mobility transistor (HEMT) biochips with high sensitivity and specificity were constructed and applied to screen the active components. Finally, the results from HEMT biochips screening were validated via in silico (molecular docking and molecular dynamics simulation), in vitro (RBL-2H3 cells), and in vivo (PCA mice model) assays. RESULTS: GMK showed a potent therapeutic effect on AR mice, and fifteen components were identified from the medicated plasma. Furthermore, hamaudol was firstly found to selectively inhibit the Syk and Lyn, and emodin was to selectively inhibit Lyn, which were further confirmed by isothermal titration calorimetry, molecular docking, and molecular dynamics simulation analyses. Suppression of the activation of FcεRI-MAPK signals might be the possible mechanism of the anti-allergic effect of hamaudol. CONCLUSIONS: The targets of emodin and hamaudol were discovered by HEMT biochips for the first time. This study provided a novel and effective strategy to discover active components in a complex herbal formula by using AlGaN/GaN HEMT biochips.

[Inhibitory effect of three strains of biocontrol microbes on pathogens causing rhizome rot of Polygonatum cyrtonema].

Rhizome rot is one of the main disease in the cultivation of Polygonatum cyrtonema, and it is also a global disease which seriously occurs on the perennial medicinal plants such as Panax notoginseng and P. ginseng. There is no effective control method at present. To identify the effects of three biocontrol microbes(Penicillium oxalicum QZ8, Trichoderma asperellum QZ2, and Brevibacillus amyloliquefaciens WK1) on the pathogens causing rhizome rot of P. cyrtonema, this study verified six suspected pathogens for their pathogenicity on P. cyrtonema. The result showed that Fusarium sp. HJ4, Colletotrichum sp. HJ4-1, and Phomopsis sp. HJ15 were the pathogens of rhizome rot of P. cyrtonema, and it was found for the first time that Phomopsis sp. could cause rhizome rot P. cyrtonema. Furthermore, the inhibitory effects of biocontrol microbes and their secondary metabolites on three pathogens were determined by confrontation culture. The results showed that the three tested biocontrol microbes significantly inhibited the growth of three pathogens. Moreover, the secondary metabolites of T. asperellum QZ2 and B. amyloliquefaciens WK1 showed significant inhibition against the three pathogens(P<0.05), and the effect of B. amyloliquefaciens WK1 sterile filtrate was significantly higher than that of high tempe-rature sterilized filtrate(P<0.05). B. amyloliquefaciens WK1 produced antibacterial metabolites to inhibit the growth of pathogens, and the growth inhibition rate of its sterile filtrate against three pathogens ranged from 87.84% to 93.14%. T. asperellum QZ2 inhibited the growth of pathogens through competition and antagonism, and P. oxalicum QZ8 exerted the inhibitory effect through competition. The research provides new ideas for the prevention and treatment of rhizome rot of P. cyrtonema and provides a basis for the di-sease control in other crops.

Monoterpenoid indole alkaloid adducts and dimers from Melodinus fusiformis.

Eight unprecedented monoterpenoid indole alkaloid (MIA) adducts and dimers, melofusinines A-H (1-8), and three undescribed melodinus-type MIA monomers, melofusinines I-K (9-11), together with six putative biogenetic precursors were isolated from the twigs and leaves of Melodinus fusiformis Champ. ex Benth. Compounds 1 and 2 are unusual hybrid indole alkaloids incorporating an aspidospermatan-type MIA with a monoterpenoid alkaloid unit via C-C coupling. Compounds 3-8 feature the first MIA dimers constructed through an aspidospermatan-type monomer and a rearranged melodinus-type monomer with two different types of couplings. Their structures were elucidated by spectroscopic data, single crystal X-ray diffraction, and calculated electric circular dichroism spectra analysis. In addition, dimers 5 and 8 showed significant neuroprotection effects on MPP +-injured primary cortical neurons.

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing.

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin.

In the last 2 decades, pathogens originating in animals may have triggered three coronavirus pandemics, including the coronavirus disease 2019 pandemic. Thus, evaluation of the spillover risk of animal severe acute respiratory syndrome (SARS)-related coronavirus (SARSr-CoV) is important in the context of future disease preparedness. However, there is no analytical framework to assess the spillover risk of SARSr-CoVs, which cannot be determined by sequence analysis alone. Here, we established an integrity framework to evaluate the spillover risk of an animal SARSr-CoV by testing how viruses break through key human immune barriers, including viral cell tropism, replication dynamics, interferon signaling, inflammation, and adaptive immune barriers, using human ex vivo lung tissues, human airway and nasal organoids, and human lung cells. Using this framework, we showed that the two pre-emergent animal SARSr-CoVs, bat BtCoV-WIV1 and pangolin PCoV-GX, shared similar cell tropism but exhibited less replicative fitness in the human nasal cavity or airway than did SARS-CoV-2. Furthermore, these viruses triggered fewer proinflammatory responses and less cell death, yet showed interferon antagonist activity and the ability to partially escape adaptive immune barriers to SARS-CoV-2. Collectively, these animal viruses did not fully adapt to spread or cause severe diseases, thus causing successful zoonoses in humans. We believe that this experimental framework provides a path to identifying animal coronaviruses with the potential to cause future zoonoses. IMPORTANCE Evaluation of the zoonotic risk of animal SARSr-CoVs is important for future disease preparedness. However, there are misconceptions regarding the risk of animal viruses. For example, an animal SARSr-CoV could readily infect humans. Alternately, human receptor usage may result in spillover risk. Here, we established an analytical framework to assess the zoonotic risk of SARSr-CoV by testing a series of virus-host interaction profiles. Our data showed that the pre-emergent bat BtCoV-WIV1 and pangolin PCoV-GX were less adapted to humans than SARS-CoV-2 was, suggesting that it may be extremely rare for animal SARSr-CoVs to break all bottlenecks and cause successful zoonoses.

A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

Glycosylation of the polyphenols from Resina draconis by glycosyltransferase YjiC1.

Resina Draconis (RD), also known as 'dragon's blood', contains a broad range of natural compounds, such as flavonoids, stilbenes and dihydrochalcones. It is clinically used to enhance blood circulation. However, the major components of RD suffer from relatively poor water solubility. Glycosylation is a critical determinant for modulating solubility and improving bioavailability and bioactivity of natural products. Herein, we report a novel method to efficiently synthesize glycosidic derivatives of the major polyphenols in RD using a microbial glycosyltransferase, i.e., YjiC1. Solubility test showed that the synthetic glycosidic derivatives displayed higher water solubility than the raw materials. This research sheds light on the structural modification of natural products for higher water solubility, which is important for innovative drug discovery.

Animal model-based simulation training for three emergent and urgent operations of penetrating thoracic injuries.

PURPOSE: To develop animal models of penetrating thoracic injuries and to observe the effects of the animal model-based training on improving the trainees' performance for emergent and urgent thoracic surgeries. METHODS: With a homemade machine, animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage, urgent sternotomy, and emergent thoracotomy. Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of animal models. Five operation teams from basic-level hospitals (group A) and five operation teams from level III hospitals (group B) were included to be trained and tested. Testing standards for the operations were established after thorough literature review, and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Tests were carried out after the training. Pre- and post-training performances were compared. Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches. RESULTS: Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%. After literature review, testing standards were established, and expert questionnaire results showed that the scientific score was 7.30 ± 1.49, and the feasibility score was 7.50 ± 0.89. Post-training performance was significantly higher in both group A and group B than pre-training performance. Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury. CONCLUSIONS: Animal model-based simulation training established in the current study could improve the trainees' performance for emergent and urgent thoracic surgeries, especially of the surgical teams from basic-level hospitals.

Hemostatic Effects of Bio-Zeolite Gauze and QuikClot Combat Gauze on Major Bleeding in Rabbits Acutely Exposed to High Altitude.

Objective: Hemostatic gauze application is an effective way to control major bleeding, which is the most common cause of death in trauma in both civilian and military settings. Coagulation derangement after acute exposure to high altitude might alter the effects of hemostatic gauzes. The present study aimed to observe the hemostatic effects of bio-zeolite gauze (BZG) and QuikClot Combat Gauze® (QCG) on major bleeding in rabbits acutely exposed to high altitude.Methods: Sixty rabbits were randomly and evenly divided into six groups. Animal models of simulated blast- and fragment-induced inguinal major bleeding were prepared in lower altitude and high-altitude areas, and BZG, QCG, and ordinary gauze without hemostatic material were used to control bleeding. The primary outcomes included immediate hemostasis rate, blood loss, and survival rate, while the secondary outcomes included hemodynamic parameters, laboratory examinations, and coagulation-relevant markers.Results: The overall effects of BZG and QCG were better than those of ordinary gauze, with a higher immediate hemostatic rate, less blood loss, and higher survival rate at 90 min after gauze application and higher red blood cell and platelet counts and lower creatinine level at 30 min after gauze application in lower altitude. The concentrations of coagulation factor XII and factor X in rabbits acutely exposed to high altitude were significantly lower than those in lower altitude. At high altitude, the hemostatic effects of BZG did not decrease significantly compared to those in the lower altitude, whereas those of ordinary gauze and QCG decreased significantly at high altitude compared to those in the lower altitude.Conclusions: Coagulation derangement after acute exposure to high altitude has negative effects on ordinary gauze and QCG but has no significant negative hemostatic effects on BZG.