An engineered self-biomineralized oncolytic adenovirus induces effective antitumor immunity and synergizes with immune checkpoint blockade.

Oncolytic adenoviruses (oADV) are promising cancer treatment agents. However, in vivo hepatic sequestration and the host immunological response against the agents limit the therapeutic potential of oADVs. Herein, we present a combined, rational design method for improving oADV infection efficiency, immunogenicity, and treatment efficacy by self-biomineralization. We integrated the biomimetic nucleopeptide W6p into the capsid of oADV using reverse genetics, allowing calcium phosphate mineralization to be biologically induced on the surface of oADV under physiological conditions, resulting in a mineral exterior. This self-biomineralized, modified oADV (oADV-W6-CaP) enhanced infection efficiency and therapeutic efficacy in coxsackie and adenovirus receptor (CAR)-negative cancer cells while protecting them against neutralization by pre-existing neutralizing antibodies. In subcutaneous mouse tumor models, systemic injection of oADV-W6-CaP demonstrated improved antitumor effectiveness, which was associated with increased T-cell infiltration and CD8+ T-cell activation. In addition, the anticancer immune response elicited by oADV-W6-CaP was dependent on CD8+ T cells, which mediated long-term immunological memory and systemic antitumor immunity against the same tumor. Finally, the addition of PD-1 or CD47 inhibition boosted the anticancer effects of oADV-W6-CaP and raised the rate of complete tumor clearance in tumor-bearing animals. The self-biomineralized oADV shifted the suppressive tumor microenvironment from a "cold" state to a "hot" state and synergized with immune checkpoint blockade to exert outstanding tumoricidal effects, demonstrating promising potential for cancer immunotherapy.

Impact of PM2.5 exposure in old age and its interactive effect with smoking on incidence of diabetes.

PURPOSE: To determine the impact of PM2.5 exposure in old age and its interactive effect with smoking on incident diabetes. METHODS: A total of 2766 participants aged ≥60 years in China were interviewed at baseline for disease risk factors in 2001-03 and were then followed up for 10 years to document incident diabetes. They were assessed for daily PM2.5 exposure in 2005. Multivariate Cox regression models were used to examine the association of PM2.5 exposure with incident diabetes and interactive effect between PM2.5 and smoking on incident diabetes. RESULTS: During the cohort follow-up, 176 participants developed diabetes. The incidence of diabetes increased with PM2.5 exposure; the multiple-adjusted hazard ratio (HR) of diabetes was 2.27 (95 % CI 1.36-3.77) in participants with PM2.5 at ≥62.0 µg/m3 compared to those with <62.0 µg/m3. There was a significant interaction effect of PM2.5 with smoking on increased risk of diabetes. The adjusted HR for participants exposed to PM2.5 levels ≥62.0 µg/m3 who smoked was 4.39 (95 % CI 1.72-11.21), while for non-smokers it was 1.65 (95 % CI 0.88-3.09), compared to those with <62.0 µg/m3. CONCLUSIONS: Exposure to PM2.5 in old age was associated with an increased incidence of diabetes and smoking enhanced the impact of PM2.5 on diabetic risk. These findings underscore the urgent need for air quality improvement measures and smoking cessation programs to mitigate the risk of diabetes in aging populations.

Cumulative effects of experimental nitrogen deposition on soil chemistry in a desert steppe: A 12-year field study.

Although the effects of human-enhanced atmospheric nitrogen (N) deposition are well documented, the response of dryland soils to N deposition remains unclear owing to the divergence in hydrological outputs and soil heterogeneity. We selected a typical desert steppe in western China to simulate the effects of long-term N deposition by applying 0 (CK), 3.5, 7, and 14 g N m-2 yr-1 for 12 consecutive years. We found that, compared with the CK plots, the total N content of the upper (0-10 cm) and lower (10-20 cm) soil layers in fertilized plots increased by 8.3-14.6 % and 2.4-8.2 %, respectively. Correspondingly, the available, NH4+-, and NO3--N contents in the upper soil significantly increased by 25.5-68.3 %. However, in the lower soil, available and NO3--N contents were significantly lower than those in the CK plots, and their variation trend was opposite to that of NH4+-N, implying N turnover and leaching. As a result, the upper and lower soil pH in fertilized plots significantly decreased by 0.36-0.53 and 0.31-0.37 units; however, their CaCO3 content significantly increased by 9.8-22.8 % and 7.2-30.3 %, respectively. The total phosphorus (P) content in the upper and lower soil layers in fertilized plots significantly increased and decreased by 3.6-51.3 % and 16.7-62.5 %, respectively, however, both significantly decreased along the N fertilization gradient. Furthermore, the upper and lower soil organic carbon (SOC) content in the fertilized plots significantly increased by 57.7-78.1 % and 19.2-27.4 %, respectively. Pearson's correlation analysis revealed that available soil P was significantly negatively correlated with plant shoot Mn content (a proxy for rhizosphere carboxylates), whereas dissolved OC, SOC, and CaCO3 were significantly positively correlated, suggesting that Ca cycling is involved in P cycling and SOC sequestration. Our study suggests that long-term N input exacerbates P limitation in desert steppes, however, enhances SOC sequestration.

Molecular Dynamics Study on Adsorption and Desorption of the Model Oligosaccharide above Polymer Antifouling Membranes.

Polysaccharide foulants play a key role in the adhesion of many fouling organisms, which may cause severe marine biofouling. However, the detailed interaction mechanism between polysaccharides and antifouling membranes is still indistinct compared with that between the fouling protein and antifouling surfaces. In this paper, a model oligosaccharide built based on the monosaccharide composition found in diatom extracellular polymeric substances (EPS) was used as a model foulant to investigate its adsorption and desorption above three T4 antifouling membranes. It was found that the anionic poly(3-(methacryloyloxy)propane-1-sulfonate) (T4-SP) antifouling membrane had excellent antifouling ability with respect to the model oligosaccharide, while the oligosaccharide can be easily adsorbed on the poly(2-(dimethylamino)ethyl methacrylate) (T4-DM) membrane with vdW attraction and on the zwitterionic poly(sulfobetaine methacrylate) (T4-SB) membrane with electrostatic attraction. As little is known about the details of polysaccharides' adsorption above antifouling membranes at the molecular level, we hope this work will serve as a theoretical basis for finding more effective materials to prevent or control marine biofouling.

Effects of biodegradable microplastics coexistence with biochars produced at low and high temperatures on bacterial community structure and phenanthrene degradation in soil.

The increasing use of biodegradable plastics may result in more serious pollution of microplastics which often coexist with biochar in soil, this will affect how organic pollutants move and transform in the soil. This work investigated the effect of biodegradable polybutylene adipate-co-terephthalate (PBAT) coexistence with biochars produced at temperatures of 400 and 700 °C (W4 and W7) on soil bacterial communities and phenanthrene degradation. The results showed that coexistence of PBAT and biochar paticles greatly boosted the relative abundance of Nocardioides while decreased the relative abundance of Sphingomonas as compared to soils with a single addition of PBAT or biochar. Changes in soil Eh values were the most influential factor in bacterial communities (more than 40% contribution). The degradation ratio of phenanthrene when PBAT coexisted with W7 (39.6 ± 3.6%) was not significantly different from the treatment with a single W7 addition (35.0 ± 2.3%, P＞0.05), and was related to phenanthrene degradation in the adsorbed state of W7 in soil. In contrast, the degradation ratio of phenanthrene in PBAT coexisting with W4 (35.1 ± 3.5%) was intermediate between that of single PBAT (49.8 ± 0.9%) and W4 (13.7 ± 5.8%) treatments. This was primarily due to changes in the experiment's initial bioavailable phenanthrene content. Furthermore, after the introduction of earthworms, phenanthrene degradation ratio in coexistence treatments were very similar to that described above in the absence of earthworms. Except for two treatments that contain W7, phenanthrene degradation ratio in the other treatments was increased by the presence of earthworms (up to 23%), which is related to the enhanced relative abundance of polycyclic aromatic hydrocarbon-degraders. Our findings indicated that PBAT coexistence with high-temperature or low-temperature biochar had a completely different impact on bacterial communities and phenanthrene degradation in soil.

Proteomics and metabolomics analyses of urine for investigation of gallstone disease in a high-altitude area.

BACKGROUND: The incidence of gallstones is high in Qinghai Province. However, the molecular mechanisms underlying the development of gallstones remain unclear. METHODS: In this study, we collected urine samples from 30 patients with gallstones and 30 healthy controls. The urine samples were analysed using multi-omics platforms. Proteomics analysis was conducted using data-independent acquisition, whereas metabolomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Among the patients with gallstones, we identified 49 down-regulated and 185 up-regulated differentially expressed proteins as well as 195 up-regulated and 189 down-regulated differentially expressed metabolites. Six pathways were significantly enriched: glycosaminoglycan degradation, arginine and proline metabolism, histidine metabolism, pantothenate and coenzyme A biosynthesis, drug metabolism-other enzymes, and the pentose phosphate pathway. Notably, 10 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers. CONCLUSION: The findings of our metabolomics and proteomics analyses provide new insights into novel biomarkers for patients with cholelithiasis in high-altitude areas.

Effect of Exercise Modality on Heart Rate Variability in Adults: A Systematic Review and Network Meta-Analysis.

Background: The purpose of this study was to use a network meta-analysis (NMA) to compare the effects of aerobic training (AT), resistance training (RT), combined training (CBT), and high-intensity interval training (HIIT) on adult heart rate variability (HRV). Methods: We searched PubMed, the Cochrane Library, Embase, the Web of Science, Wanfang Data, and the China National Knowledge Infrastructure to identify randomized controlled trials on the effects of exercise on HRV in adults. The search was conducted from the outset of these databases to April 2023. Two reviewers independently screened the retrieved articles, extracted raw data from the relevant studies, and assessed the possible risk of bias in the included studies. Results: The NMA showed that HIIT had the greatest effect on the low-frequency (LF) power/high-frequency (HF) power ratio, standard deviation of normal-normal intervals (SDNN), and root mean square of successive differences between adjacent normal-to-normal intervals (RMSSD) (surface under the cumulative ranking curve (SUCRA) = 99.75%, 98.7%, and 84.9%); CBT had the greatest effect on the LF power (SUCRA = 66.3%); RT had the greatest effect on the HF power (SUCRA = 72.5%). Conclusions: Our NMA and SUCRA ranking results suggest that in adults, HIIT is the most effective exercise modality in improving the SDNN, RMSSD, and LF/HF power ratio; RT for the HF power; CBT for the LF power. Any NMA conducted in the future must fully explore the effects of different exercise modalities on HRV in adult subgroups of different ages and genders. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=424054, identifier: CRD42023424054.

Therapeutic potential of ASK1 activators in cancer treatment: Current insights and future directions.

Apoptosis signal-regulated kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase (MAP3K) family, whose activation and regulation are intricately associated with apoptosis. ASK1 is activated in response to oxidative stress, among other stimuli, subsequently triggering downstream JNK, p38 MAPK, and mitochondria-dependent apoptotic signaling, which participate in the initiation of tumor cell apoptosis induced by various stimuli. Research has shown that ASK1 plays a crucial role in the apoptosis of lung cancer, breast cancer, and liver cancer cells. Currently, the investigation of effective ASK1 activators is a hot topic in research on tumor cell apoptosis. Synthetic compounds such as human ß-defensin, triazolothiazide derivatives and heat shock protein 27 inhibitors; natural compounds such as quercetin, Laminarina japonica polysaccharide-1 peptide and theabrownin; and nanomedicines such as cerium oxide nanoparticles, magnetite FeO nanoparticles and silver nanoparticles can activate ASK1 and induce apoptosis in various tumor cells. This review extensively investigates the roles and activation mechanisms of ASK1, explores its impact on a variety of apoptotic signaling pathways, and discusses the potential therapeutic applications of various ASK1 activators in cancer treatment. In addition, this paper provides an in-depth discussion of the future development of this field and proposes a promising method for further research and clinical progress.

Magnetic MOF composites for the electrocatalysis and biosensing of dopamine released from living cells.

Metal-organic frameworks (MOFs) with fit ligands and metals can be integrated into electrochemical biosensors for the detection of various biomolecules. In this study, we have synthesized novel magnetic MOF composites as electrocatalysts and constructed a novel biosensor for electrochemical detection of dopamine. The composites named Fe3O4@ZIF-8@AuNPs-COOH are synthesized through layer-by-layer assembly. They exhibit excellent stability and cooperative catalytic activity. In addition, green recycling is readily achieved through magnetizing/demagnetizing the electrode. The large specific surface area and ordered porous structures of the magnetic MOFs ensure good dispersion of gold nanoparticles, while the carboxyl group efficiently shields other redox-active interfering substances. The proposed electrochemical biosensor accomplishes the sensitive detection of dopamine in human serums and living cells. This study broadens the application of MOFs in electrochemical biosensing, validates the feasibility of biosensors for in vivo analysis, and provides new insights into green sensing.

Postmenopausal giant uterine adenomyoma with adipose metaplasia: A case report and literature review.

RATIONALE: Uterine adenomyomas (UAs) are common benign tumors, usually not exceeding 280 g or the weight of the uterus at 12 weeks gestation. Postmenopausal giant UAs of diameter larger than 20 cm are rare, as well as steatosis, but curable by surgical excision. Few cases of postmenopausal giant UAs have been reported. PATIENT CONCERNS: Herein, we report a case of a 70-year-old female patient who presented with a giant pelvic tumor of about 20 cm × 18 cm × 20 cm with postmenopausal vaginal bleeding, and whose radiographic manifestations did not exclude the possibility of uterine malignancy. DIAGNOSES: Histopathology confirms an adenomyoma with partial adipose metaplasia. INTERVENTIONS: We did an open laparotomy of hysterectomy, bi-adnexectomy, and pelvic adhesion release for the patient. OUTCOMES: Pathology revealed adenomyoma with adipose metaplasia. The patient recovered well and was discharged on postoperative day 7 with satisfactory follow-up.

[Research Progress of Antibiotic Resistance Genes Removal in Food Waste During Anaerobic Digestion].

Food waste is one of the important reservoirs of antibiotic resistance genes （ARGs）, and its resource utilization has potential environmental risks. Anaerobic digestion （AD） technology can concurrently achieve resource recovery and ARGs removal, which is one of the popular resource technologies for food waste management. However, the removal efficiency of ARGs during the AD process is limited, and thus the safety of digestate for agricultural use is still questioned. Therefore, how to improve the performance of ARGs removal during the AD process is critical for efficient and environmentally friendly bioconversion of food waste. This study summarized the transmission pathways and mechanisms of ARGs in food waste； discussed the effects of different operation parameters on the transmission of ARGs in food waste during the AD process； described the research progress of exogenous addition of conductive materials, feedstock pretreatment, etc., strategies to enhance the removal of ARGs； and analyzed the migration regularity and removal mechanism of ARGs in food waste during the AD process, which mainly included microbial community structure evolution, mobile genetic element changes, and environmental factor changes. Finally, this study prospected the future improvement of methane yield and ARGs removal in the AD process of food waste based on the existing research.

Ruptured primary ovarian pregnancy: A case report with a literature review.

RATIONALE: Ovarian pregnancy is a rare form of ectopic pregnancy, accounting for 0.5% to 3% of the total number of ectopic pregnancies. Its diagnostic rate is very low and it can be easily misdiagnosed before laparoscopy, due to the clinical presentation being very similar to tubal pregnancy. The ovarian blood supply is abundant, and in case of rupture of ovarian pregnancy, intra-abdominal hemorrhage or even hemorrhagic shock may occur, endangering the patient's life. We report a case of ruptured primary ovarian pregnancy through natural conception. PATIENT CONCERNS: This patient had a history of menopause with lower abdominal pain and tenderness. Ultrasound showed a thick-walled cystic echo in the left adnexal region, a dark area of fluid in the pelvis, and an irregular, slightly strong echo posterior to the uterus. Unclotted blood was punctured from the posterior fornix, and her hemoglobin was decreasing with a serum ß-human chorionic gonadotropin of 1800.00 mIU/mL. DIAGNOSES: Through early recognition of clinical manifestations, ultrasonography, laparoscopic exploration, and the final histopathologic examination, this patient was diagnosed with an ovarian pregnancy. INTERVENTIONS: Then, removal of the left ovarian pregnancy lesion was performed, which was visible as villi. And Methotrexate 50 mg was administered locally. OUTCOMES: Through conservative surgical treatment, she recovered well and was discharged with a satisfactory follow-up. LESSONS: Gynecologists should be alert to patients with menopausal lower abdominal pain with or without vaginal bleeding and consider ectopic pregnancy in rare sites, such as ovarian pregnancy. Surgery is the mainstay of treatment, and early laparoscopic exploration may be beneficial in clarifying the diagnosis and performing the concurrent surgical treatment.

Isolation and purification of carbohydrate components in functional food: a review.

Medicinal plants, increasingly utilized in functional foods, possess potent therapeutic properties and health-promoting functions, with carbohydrates playing a crucial role and exhibiting a range of effects, such as antioxidant, antitumor, immune-enhancing, antibacterial, anticoagulant, and hypoglycemic activities. However, comprehensively, accurately, rapidly, and economically assessing the quality of carbohydrate components is challenging due to their diverse and complex nature. Additionally, the purification and identification of carbohydrates also guarantee related efficacy research. This paper offers a thorough review of research progress carried out by both domestic and international scholars in the last decade on extracting, purifying, separating, identifying, and determining the content of carbohydrate components from functional foods, which are mainly composed of medicinal plants, and also explores the potential for achieving comprehensive quantitative analysis and evaluating structure-activity relationships of carbohydrate components. These findings aim to serve as a valuable reference for the future development and application of natural carbohydrate components in functional food and medicine.

The Dynamic Modulation Doping Effect of Gas Molecules on an AlGaN/GaN Heterojunction Surface.

AlGaN/GaN high-electron-mobility transistors (HEMTs) are widely used in high-frequency and high-power applications owing to the high two-dimensional electron gas (2DEG) concentration. However, the microscopic origin of the 2DEG remains unclear. This hinders the development of device fabrication technologies, such as threshold voltage modulation, current collapse suppression, and 2DEG concentration enhancement technologies, as well as AlGaN/GaN sensors with very high sensitivity to polar liquids. To clarify the 2DEG microscopic origin, we studied the effects of gas molecules on AlGaN/GaN surfaces through various experiments and first-principles calculations. The results indicated that the adsorption of gas molecules on the AlGaN/GaN surface is an important phenomenon, clarifying the microscopic origin of the 2DEG. This study elucidates the properties of AlGaN/GaN heterojunctions and promotes the development of new fabrication technologies for AlGaN/GaN devices.

Harnessing plant-beneficial bacterial encapsulation: A sustainable strategy for facilitating cadmium bioaccumulation in Medicago sativa.

Plant-beneficial bacteria (PBB) have emerged as a promising approach for assisting phytoremediation of heavy metal (HM)-contaminated soils. However, their colonization efficiency is often challenged by complex soil environments. In this study, we screened one rhizobacterium (Klebsiella variicola Y38) and one endophytic bacterium (Serratia surfactantfaciens Y15) isolated from HM-contaminated soils and plants for their high resistance to Cd and strong growth-promoting abilities. These strains were encapsulated individually or in combination with alginate and applied with Medicago sativa in Cd-contaminated soil pot experiments. The effectiveness of different bacterial formulations in promoting plant growth and enhancing Cd bioconcentration in M. sativa was evaluated. Results showed that PBB application enhanced plant growth and antioxidant capacity while reducing oxidative damage. Encapsulated formulations outperformed unencapsulated ones, with combined formulations yielding superior results to individual applications. Quantitative PCR indicated enhanced PBB colonization in Cd-contaminated soils with alginate encapsulation, potentially explaining the higher efficacy of alginate-encapsulated PBB. Additionally, the bacterial agents modified Cd speciation in soils, resulting in increased Cd bioaccumulation in M. sativa by 217-337 %. The alginate-encapsulated mixed bacterial agent demonstrated optimal effectiveness, increasing the Cd transfer coefficient by 3.2-fold. Structural equation modeling and correlation analysis elucidated that K. variicola Y38 promoted Cd bioaccumulation in M. sativa roots by reducing oxidative damage and enhancing root growth, while S. surfactantfaciens Y15 facilitated Cd translocation to shoots, promoting shoot growth. The combined application of these bacteria leveraged the benefits of both strains. These findings contribute to diversifying strategies for effectively and sustainably remediating Cd-contaminated soils, while laying a foundation for future investigations into bacteria-assisted phytoremediation.

Photocrosslinked carboxymethylcellulose-based hydrogels: Synthesis, characterization for curcumin delivery and wound healing.

Skin could protect our body and regenerate itself to against dysfunctional and disfiguring scars when faced with external injury. As wound dressings, hydrogels are biocompatible, hydrophilic and have a 3D structure similar to the extracellular matrix (ECM). In particular, hydrogels with drug-releasing capabilities are in acute wound healing. In this paper, photocrosslinked hydrogels served as wound dressing based on sodium carboxymethylcellulose (CMC) were prepared to promote wound healing. Photocrosslinked hydrogels were prepared by grafting lysine and allyl glycidyl ether (AGE) onto CMC and encapsulating curcumin (Cur). The synthesized hydrogels had the unique 3D porous structure with a swelling ratio up to 1300 % in aqueous solution. The drug release ratios of the hydrogels were 20.8 % in acid environment, and 14.4 % in alkaline environment. Notably, the hydrogels showed good biocompatibility and antibacterial properties and also exhibited the ability to accelerate the process of skin wound healing while prevent inflammation and scar formation when applied to a mouse skin wound model. As a result, the prepared hydrogels Gel-CLA@Cur showed great potential in wound healing.

Optimizing Prediction of In-Hospital Mortality in Elderly Patients With Acute Myocardial Infarction: A Nomogram Approach Using the Age-Adjusted Charlson Comorbidity Index Score.

BACKGROUND: To study the age-adjusted Charlson comorbidity index (ACCI) scale, which is a comprehensive quantification of multimorbidity coexistence, for the assessment of the risk of acute myocardial infarction death in elderly people. METHODS AND RESULTS: A total of 502 older patients with acute myocardial infarction were studied at Qilu Hospital from September 2017 to March 2022. They were categorized on the basis of ACCI into low (≤5), intermediate (6, 7), and high (≥8) risk groups. Hospitalization duration was observed, with death as the end point. least absolute shrinkage and selection operator regression was used to screen variables, 10-fold cross-validation was performed to validate the screened variables, a Cox regression nomogram predicting the risk of patient death was prepared, hazard ratio with 95% CI was calculated, a nomogram calibration curve was constructed, and a receiver operating characteristic curve, decision curve analysis, and a clinical impact curve were established. From 62 potential factors in a least absolute shrinkage and selection operator regression, 12 were selected via 10-fold cross-validation. Retain variables with significant statistical differences in the Cox regression. A nomogram of the risk of death from acute infarction was constructed, and risk factors included ventricular tachycardia/fibrillation, atrial fibrillation, nicorandil, angiotensin-converting enzyme inhibitors/angiotensin-converting enzyme inhibitors, ß blockers, and ACCI score, carbon dioxide combining power, and blood calcium concentration. CONCLUSIONS: The ACCI score effectively assesses multimorbidity in the older patients. As ACCI rises, the death risk from acute myocardial infarction grows. The study's nomogram is valid and clinically applicable.

A thermodynamic model of the surface hydroxylation of γ-Al2O3.

Rational design of γ-alumina-based catalysts relies on an extensive understanding of the distribution of hydroxyl groups on the surface of γ-alumina and their physicochemical properties, which remain unclear and challenging to determine experimentally due to the structural complexity. In this work, by means of DFT and thermodynamic calculations, various hydroxylation modes of γ-alumina (110) and (100) surfaces at different OH coverages were evaluated, based on which a thermodynamic model to reflect the relationship between temperature and the surface structure was established and the stable hydroxylation modes under experimental conditions were predicted. This enables us to identify the experimentally measured IR spectra. The effect of hydroxyl coverages on the surface Lewis acidity was then analyzed, showing that the presence of hydroxyl groups could promote the Lewis acidity of neighboring Al sites. This work provides fundamental insights into the molecular level understanding of the surface properties of γ-alumina and benefits the rational design of alumina-based catalysts.

Fatty Acids and Volatile Flavor Components of Adipose Tissue from Local Tibetan Sheep in Qinghai with Dietary Supplementation of Palm Kernel Meal (PKM).

Substituting traditional protein feed with palm kernel meal (PKM) in the diet of Tibetan sheep can be a cost-effective feeding strategy. To determine the impact of PKM on flavor development in different adipose tissues of Tibetan sheep, subjects were fed with 15% and 18% of PKM, while the control group received no PKM. The fatty acids and volatile compounds in the samples were then analyzed by GC-MS and HS-GC-IMS. Adding PKM to the diet significantly increased the C12:0, C14:0, C16:0 and C18:1N9 content in adipose tissues compared with the control, and most of these were associated with flavor formation (p < 0.05). The flavor compounds in the adipose tissues predominantly consisted of alcohols, ketones, acids and aldehydes. In particular, including PKM in the diet increased the proportion of ketones but decreased the proportion of alcohols, acids and aldehydes in subcutaneous and tail fat. Specifically, the proportion of acetone, acetoin monomer, 2,3-butanedione, 2-butanone monomer, 2-methyl-2-propanol, 2-methyl-2-propanol and methyl acetate increased significantly in the subcutaneous and tail fat (p < 0.05), while that of ethanol, 1-propanol monomer, butanol monomer, acetic acid monomer and acetic acid monomer decreased. Intermuscular fat exhibited variable results, mainly because the addition of PKM resulted in higher proportions of alcohols, including ethanol, 1-propanol and butanol monomer, especially at 15% PKM. In summary, the addition of PKM improved the flavor of Tibetan sheep fat and increased the amount of favorable volatile flavor compounds. This study can serve as reference for understanding the effects of dietary PKM on the adipose tissue flavor profile of Tibetan sheep.

Spinal muscular atrophy caused by compound heterozygous SMN1 mutations: two cases and literature review.

Spinal muscular atrophy (SMA) is a rare neuromuscular disease, which is characterized by the degeneration of motor neurons, leading to symmetrical muscle weakness and atrophy. Description of two novel SMN1 mutations (patient1: c.683T > A, p.Leu228Ter; patient2: c.347 T > C, p.Ile116 Thr). We reported two patients with SMN1 mutations with the clinical features, and provided a literature review of the previously reported 22 cases. Two SMA patients showed progressive proximal lower limb weakness and milder clinical symptom. In a total of 22 cases, the most commonly observed SMN1 gene alteration was missense mutation (55%), followed by splicing defect (27%), nonsense (9%) and frameshift (9%). We discuss the possible decisive role of these intragenic mutations in the phenotypic results, which enriched the SMN 1 fine mutation database.