Semi-Ionic F Modified N-Doped Porous Carbon Implanted with Ruthenium Nanoclusters toward Highly Efficient pH-Universal Hydrogen Generation.

Developing high electroactivity ruthenium (Ru)-based electrocatalysts for pH-universal hydrogen evolution reaction (HER) is challenging due to the strong bonding strengths of key Ru─H/Ru─OH intermediates and sluggish water dissociation rates on active Ru sites. Herein, a semi-ionic F-modified N-doped porous carbon implanted with ruthenium nanoclusters (Ru/FNPC) is introduced by a hydrogel sealing-pyrolying-etching strategy toward highly efficient pH-universal hydrogen generation. Benefiting from the synergistic effects between Ru nanoclusters (Ru NCs) and hierarchically F, N-codoped porous carbon support, such synthesized catalyst displays exceptional HER reactivity and durability at all pH levels. The optimal 8Ru/FNPC affords ultralow overpotentials of 17.8, 71.2, and 53.8 mV at the current density of 10 mA cm-2 in alkaline, neutral, and acidic media, respectively. Density functional theory (DFT) calculations elucidate that the F-doped substrate to support Ru NCs weakens the adsorption energies of H and OH on Ru sites and reduces the energy barriers of elementary steps for HER, thus enhancing the intrinsic activity of Ru sites and accelerating the HER kinetics. This work provides new perspectives for the design of advanced electrocatalysts by porous carbon substrate implanted with ultrafine metal NCs for energy conversion applications.

Elucidating High Initial Coulombic Efficiency, Pseudocapacitive Kinetics and Charge Storage Mechanism of Antiperovskite Carbide Ni3ZnC0.7@rGO Anode for Fast Sodium Storage in Ether Electrolyte.

To explore novel electrode materials with in-depth elucidation of initial coulombic efficiency (ICE), kinetics, and charge storage mechanisms is of great challenge for Na-ion storage. Herein, a novel 3D antiperovskite carbide Ni3ZnC0.7@rGO anode coupled with ether-based electrolyte is reported for fast Na-ion storage, exhibiting superior performance than ester-based electrolyte. Electrochemical tests and density functional theory (DFT) calculations show that Ni3ZnC0.7@rGO anode with ether-based electrolyte can promote charge/ion transport and lower Na+ diffusion energy barrier, thereby improving ICE, reversible capacity, rate, and cycling performance. Cross-sectional-morphology and depth profiling surface chemistry demonstrate that not only a thinner and more homogeneous reaction interface layer with less side effects but also a superior solid electrolyte interface (SEI) film with a high proportion of inorganic components are formed in the ether-based electrolyte, which accelerates Na+ transport and is the significant reason for the improvement of ICE and other electrochemical properties. Meanwhile, electrochemical and ex situ measurements have revealed conversion, alloying, and co-intercalation hybrid mechanisms of the Ni3ZnC0.7@rGO anode based on ether electrolyte. Interestingly, the Na-ion capacitors (SICs) designed by pairing with activated carbon (AC) cathode exhibit favorable electrochemical performance. Overall, this work provides deep insights on developing advanced materials for fast Na-ion storage.

Mutations in SREBF1, Encoding Sterol Regulatory Element Binding Transcription Factor 1, Cause Autosomal-Dominant IFAP Syndrome.

IFAP syndrome is a rare genetic disorder characterized by ichthyosis follicularis, atrichia, and photophobia. Previous research found that mutations in MBTPS2, encoding site-2-protease (S2P), underlie X-linked IFAP syndrome. The present report describes the identification via whole-exome sequencing of three heterozygous mutations in SREBF1 in 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. SREBF1 encodes sterol regulatory element-binding protein 1 (SREBP1), which promotes the transcription of lipogenes involved in the biosynthesis of fatty acids and cholesterols. This process requires cleavage of SREBP1 by site-1-protease (S1P) and S2P and subsequent translocation into the nucleus where it binds to sterol regulatory elements (SRE). The three detected SREBF1 mutations caused substitution or deletion of residues 527, 528, and 530, which are crucial for S1P cleavage. In vitro investigation of SREBP1 variants demonstrated impaired S1P cleavage, which prohibited nuclear translocation of the transcriptionally active form of SREBP1. As a result, SREBP1 variants exhibited significantly lower transcriptional activity compared to the wild-type, as demonstrated via luciferase reporter assay. RNA sequencing of the scalp skin from IFAP-affected individuals revealed a dramatic reduction in transcript levels of low-density lipoprotein receptor (LDLR) and of keratin genes known to be expressed in the outer root sheath of hair follicles. An increased rate of in situ keratinocyte apoptosis, which might contribute to skin hyperkeratosis and hypotrichosis, was also detected in scalp samples from affected individuals. Together with previous research, the present findings suggest that SREBP signaling plays an essential role in epidermal differentiation, skin barrier formation, hair growth, and eye function.

Redox Electrolytes-Assisting Aqueous Zn-Based Batteries by Pseudocapacitive Multiple Perovskite Fluorides Cathode and Charge Storage Mechanisms.

Aqueous Zn-based batteries (AZBs) have attracted intensive attention. However, to explore advanced cathode materials with in-depth elucidation of their charge storage mechanisms, improve energy storage capacity, and construct novel cell systems remain a great challenge. Herein, a new pseudocapacitive multiple perovskite fluorides (ABF3 ) cathode is designed, represented by KMF-(IV, V, and VI; M = NiCoMnZn/-Mg/-MgFe), and constructed Zn//KMF-(IV, V, and VI) AZBs and their flexible devices. Ex situ tests have revealed a typical bulk phase conversion mechanism of KMF-VI electrode for charge storage in alkaline media dominated by redox-active Ni/Co/Mn species, with transformation of ABF3 nanocrystals into amorphous metal oxide/(oxy)hydroxide nanosheets. By employing single or bipolar redox electrolyte strategies of 20 mm [Fe(CN)6 ]3- or/and 10 mm SO3 2- /Cu[(NH3 )4 ]2+ acting on KMF-(IV, V, and VI) cathode and Zn anode, the AZBs show an improved energy storage owing to additional capacity contribution of redox electrolytes. The as-designed Zn//polyvinyl alcohol (PVA)-KOH-K3 [Fe(CN)6 ]//KMF-(IV, V, and VI) redox gel electrolytes-assisting flexible AZBs (RGE-FAZBs) exhibit remarkable performance under different bending angles because of slight dissolution corrosion of zinc anode compared with liquid electrolytes. Overall, the work demonstrates the novel idea of conversion-type multiple ABF3 cathode for redox electrolytes-assisting AZBs (RE-AZBs) and their flexible systems, showing great significance on electrochemical energy storage.

Clinical characteristics and prognostic factors in intracranial hemorrhage patients with hematological diseases.

The clinical characteristics and prognosis of intracranial hemorrhage (ICH) in patients with hematological diseases remain controversial. This study aimed to describe the clinical characteristics and explore the prognostic factors in such patients. A total of 238 ICH patients with a hematological disease were recruited from the Institute of Hematology and Blood Diseases Hospital, China, from January 2015 to April 2020. The Cox proportional hazards model was used to identify the prognostic factors for 30-day mortality in ICH patients with a hematological disease. There were 123 cases of acute leukemia (AL), 20 of myelodysplasia/myeloproliferative neoplasm, 35 of aplastic anemia (AA), 29 of immune thrombocytopenia (ITP), 19 of congenital/acquired coagulation factor deficiency, and 12 of other hematological diseases. Furthermore, 121 patients presented with a multi-site hemorrhage (MSH), 58 with a single-site hemorrhage in the brain parenchyma (PCH), 23 with a subarachnoid hemorrhage, 33 with a subdural hemorrhage (SH), and three with an epidural hemorrhage. The Cox proportional hazards model indicated association of SH (vs PCH, hazard ratio [HR]: 0.230; 95% confidence interval [CI]: 0.053-0.996; P = 0.049), low white blood cells (≤ 100 × 109/L vs > 100 × 109/L, HR: 0.56; 95% CI: 0.348-0.910; P = 0.019), AA (vs AL, HR: 0.408; 95% CI: 0.203-0.821; P = 0.012), and ITP (vs AL, HR: 0.197; 95% CI: 0.061-0.640; P = 0.007) with improved 30-day mortality. However, increased age (HR: 1.012; 95% CI: 1.001-1.022; P = 0.034), MSH (vs PCH, HR: 1.891; 95% CI: 1.147-3.117; P = 0.012), and a disturbance of consciousness (HR: 1.989; 95% CI: 1.269-3.117; P = 0.003) were associated with increased risk of 30-day mortality. In conclusion, in this study, we revealed the clinical characteristics of Chinese ICH patients with a hematological disease. Moreover, we identified risk factors (age, white blood cells, AA, ITP, SH, MSH, and a disturbance of consciousness) that may influence 30-day mortality.

BRASSINOSTEROID-SIGNALING KINASE 1 phosphorylating CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE functions in drought tolerance in maize.

Drought stress seriously limits crop productivity. Although studies have been carried out, it is still largely unknown how plants respond to drought stress. Here we find that drought treatment can enhance the phosphorylation activity of brassinosteroid-signaling kinase 1 (ZmBSK1) in maize (Zea mays). Our genetic studies reveal that ZmBSK1 positively affects drought tolerance in maize plants. ZmBSK1 localizes in plasma membrane, interacts with calcium/calmodulin (Ca2+ /CaM)-dependent protein kinase (ZmCCaMK), and phosphorylates ZmCCaMK. Ser-67 is a crucial phosphorylation site of ZmCCaMK by ZmBSK1. Drought stress enhances not only the interaction between ZmBSK1 and ZmCCaMK but also the phosphorylation of Ser-67 in ZmCCaMK by ZmBSK1. Furthermore, Ser-67 phosphorylation in ZmCCaMK regulates its Ca2+ /CaM binding, autophosphorylation and transphosphorylation activity, and positively affects its function in drought tolerance in maize. Our results reveal an important role for ZmBSK1 in drought tolerance and suggest a direct regulatory mode of ZmBSK1 phosphorylating ZmCCaMK.

ZmMPK5 phosphorylates ZmNAC49 to enhance oxidative stress tolerance in maize.

Mitogen-activated protein kinase (MPK) is a critical regulator of the antioxidant defence system in response to various stimuli. However, how MPK directly and exactly regulates antioxidant enzyme activities is still unclear. Here, we demonstrated that a NAC transcription factor ZmNAC49 mediated the regulation of antioxidant enzyme activities by ZmMPK5. ZmNAC49 expression is induced by oxidative stress. ZmNAC49 enhances oxidative stress tolerance in maize, and it also reduces superoxide anion generation and increases superoxide dismutase (SOD) activity. A detailed study showed that ZmMPK5 directly interacts with and phosphorylates ZmNAC49 in vitro and in vivo. ZmMPK5 directly phosphorylates Thr-26 in NAC subdomain A of ZmNAC49. Mutation at Thr-26 of ZmNAC49 does not affect the interaction with ZmMPK5 and its subcellular localisation. Further analysis found that ZmNAC49 activates the ZmSOD3 expression by directly binding to its promoter. ZmMPK5-mediated ZmNAC49 phosphorylation improves its ability to bind to the ZmSOD3 promoter. Thr-26 of ZmNAC49 is essential for its transcriptional activity. In addition, ZmSOD3 enhances oxidative stress tolerance in maize. Our results show that phosphorylation of Thr-26 in ZmNAC49 by ZmMPK5 increased its DNA-binding activity to the ZmSOD3 promoter, enhanced SOD activity and thereby improved oxidative stress tolerance in maize.

The transcription factor ZmNAC49 reduces stomatal density and improves drought tolerance in maize.

Drought stress severely limits the growth, development, and productivity of crops, and therefore understanding the mechanisms by which plants respond to drought is crucial. In this study, we cloned a maize NAC transcription factor, ZmNAC49, and identified its function in response to drought stress. We found that ZmNAC49 is localized in the nucleus and has transcriptional activation activity. ZmNAC49 expression is rapidly and strongly induced by drought stress, and overexpression enhances stress tolerance in maize. Overexpression also significant decreases the transpiration rate, stomatal conductance, and stomatal density in maize. Detailed study showed that ZmNAC49 overexpression affects the expression of genes related to stomatal development, namely ZmTMM, ZmSDD1, ZmMUTE, and ZmFAMA. In addition, we found that ZmNAC49 can directly bind to the promoter of ZmMUTE and suppress its expression. Taken together, our results show that the transcription factor ZmNAC49 represses ZmMUTE expression, reduces stomatal density, and thereby enhances drought tolerance in maize.

Vacant Manganese-Based Perovskite Fluorides@Reduced Graphene Oxides for Na-Ion Storage with Pseudocapacitive Conversion/Insertion Dual Mechanisms.

Na-ion capacitors (NICs) and Na-based dual-ion batteries (Na-DIBs) have been considered to be promising alternatives to traditional lithium-ion batteries (LIBs) because of the abundance and low cost of the Na-ion, but their energy density, power density and life cycle are limited. Herein, dual-vacancy (including K+ and F- vacancies) perovskite fluoride K0.86 MnF2.69 @reduced graphene oxide (rGO; recorded as Mn-G) as anode for NICs and Na-DIBs has been developed. The special conversion/intercalation dual Na-ion energy storage mechanism and pseudocapacitive dynamics are analyzed in detail. The Mn-G//AC NICs and Mn-G//KS6 Na-DIBs delivered a maximum energy density of 92.7 and 187.6 W h kg-1 , a maximum power density of 20.2 and 21.12 kW kg-1 , and long cycle performance of 61.3 and 68.4 % after 1000 cycles at 5 A g-1 , respectively. Moreover, Mn-G//AC NICs and Mn-G//KS6 Na-DIBs can work well over a wide range of temperatures (-20 to 40 °C). These results make it competitive in Na-ion storage applications with high energy/power density over a wide temperature range.

Conversion/Alloying Pseudocapacitance-Dominated Perovskite KZnF3 Anode for Advanced Lithium-Based Dual-Ion Batteries.

Cost-competitive perovskite fluoride KZnF3 has been introduced for the first time as an advanced anode for high-performance lithium-based dual-ion batteries, exhibiting conversion/alloying hybrid mechanisms and dominated pseudocapacitive kinetics for Li-ion storage.

PGM5 is a promising biomarker and may predict the prognosis of colorectal cancer patients.

BACKGROUND: Phosphoglucomutase (PGM), a key enzyme in the metabolism of glucose-1-phosphate and glucose-6-phosphate, has been found to be associated with proliferation, invasion, and metastasis of cancer. However, the expression and function of PGM5 in colorectal cancer (CRC) remains unknown. METHODS: We tested PGM5 mRNA and protein expression levels in 79 CRC tissue and their matched adjacent tissue samples by qRT-PCR and immunohistochemistry, respectively. Overall survival (OS) was estimated with the Kaplan-Meier method and compared between groups with the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk. The cell proliferation, migration and invasion abilities of CRC cells were detected by using CCK-8, Transwell migration and invasion assays, respectively. RESULTS: The PGM5 protein levels expression in CRC tissues were significantly lower than those in the adjacent tissues (t = 5.035, P < 0.001), and Kaplan-Meier analysis indicated that low PGM5 expression were significantly associated with poor overall survival (P = 0.0069). Univariate and multivariate analyses demonstrated that PGM5 was an independent risk factor for overall survival (hazard ratio = 0.3951, P = 0.014). PGM5 overexpression significantly inhibited the proliferation, invasion and migration abilities of CRC cells. On the contrary, knockdown of PGM5 promotes the invasion and migration of CRC cells. CONCLUSIONS: PMG5 regulates proliferation, invasion, and migration in the CRC and decreased PGM5 is associated with poor prognosis. Therefore, PGM5 is a promising biomarker in CRC and decreased PGM5 may predict poor overall survival in patients with CRC.

Curcumin ameliorates gestational diabetes in mice partly through activating AMPK.

CONTEXT: In vitro and in vivo research has shown that curcumin can alleviate diabetes and the relevant complications. OBJECTIVE: To investigate the effect of curcumin on gestational diabetes (GD). MATERIALS AND METHODS: C57 BL/KsJdb/+(db/+) mice and C57 BL/KsJ+/+ mice (10-12 weeks old) were divided into four groups (n = 15): normal pregnancy (C57 BL/KsJ+/+), GD (C57 BL/KsJdb/+), GD plus low dose curcumin (50 mg/kg, orally gavage every day) and GD plus high dose curcumin (100 mg/kg, orally gavage every day). The tolerance of glucose and insulin were measured on gestation day 10. Body weight at birth and litter size of offspring were investigated, and the expression of oxidative stress factors [thiobarbituric acid reactive substance (TBARS), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)] and AMP-activated protein kinase (AMPK), phospho-AMPK, histone deacetylases 4 (HDAC4), pHDAC4 and glucose-6-phosphatase (G6Pase) in the livers were analyzed by ELISA and Western blot on gestation day 20. RESULTS: High dose curcumin could partly ameliorate the intolerance of glucose and insulin, and completely restore the litter size and the body weight of GD mice through decreased TBARS expression (p < 0.05) and increased GSH, SOD and CAT expression (p < 0.05). Enhanced AMPK activation, accompanied with decreased HDAC4 and G6Pase expression (p < 0.05) were partly contributed to the alleviation of GD mediated by curcumin. CONCLUSIONS: Although further detailed mechanism needs to be deciphered, curcumin can be considered as an alternative treatment for gestational diabetes.

Simulated Sunlight-Mediated Photodynamic Therapy for Melanoma Skin Cancer by Titanium-Dioxide-Nanoparticle-Gold-Nanocluster-Graphene Heterogeneous Nanocomposites.

Simulated sunlight has promise as a light source able to alleviate the severe pain associated with patients during photodynamic therapy (PDT); however, low sunlight utilization efficiency of traditional photosensitizers dramatically limits its application. Titanium-dioxide-nanoparticle-gold-nanocluster-graphene (TAG) heterogeneous nanocomposites are designed to efficiently utilize simulated sunlight for melanoma skin cancer PDT. The narrow band gap in gold nanoclusters (Au NCs), and staggered energy bands between Au NCs, titanium dioxide nanoparticles (TiO2 NPs), and graphene can result in efficient utilization of simulated sunlight and separation of electron-hole pairs, facilitating the production of abundant hydroxyl and superoxide radicals. Under irradiation of simulated sunlight, TAG nanocomposites can trigger a series of toxicological responses in mouse B16F1 melanoma cells, such as intracellular reactive oxygen species production, glutathione depletion, heme oxygenase-1 expression, and mitochondrial dysfunctions, resulting in severe cell death. Furthermore, intravenous or intratumoral administration of biocompatible TAG nanocomposites in B16F1-tumor-xenograft-bearing mice can significantly inhibit tumor growth and cause severe pathological tumor tissue changes. All of these results demonstrate prominent simulated sunlight-mediated PDT effects.

Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL International Working Group.

The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression.

Role of miRNA in pathogenesis, diagnosis, and prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers and is responsible for the second cancer-related death globally. Many treatment regimens have been developed to cure the disease; however, life expectancy is still low. Therefore, there is an urgent need to explore new selective, specific, and robust diagnosis markers for efficient early recognition of the ailment. Along with the diagnosis, the treatment's effectiveness can be determined by prognostic markers, and miRNAs are excellent tools for the diagnosis and prognosis of HCC. In addition, the altered expression profile of a few miRNAs promotes HCC cell migration and invasion, and selective up- or downregulation of these responsible genes may help mitigate the disorder. On one hand, few of the miRNAs have been found to enhance angiogenesis, a crucial step of tumor growth; on the other hand, upregulation of specific miRNAs is reported to suppress angiogenesis and resulting tumor growth of HCC cells. Exosomal miRNAs have significant implications in promoting angiogenesis, increased endothelial cell permeability, tube formation, and metastasis to hepatic and pulmonary tissues. miRNA also attributes to drug resistance toward chemotherapy and the prevention of autophagy also. Identifying novel miRNA and determining their differential expression in HCC tissue may serve as a potential tool for diagnosis, prognosis, and therapy to enhance the life expectancy and quality of life of HCC patients. In the present review, we have summarized the recent advances in HCC-related research.

Six-year clinical evaluation of iRoot BP Plus as apical barrier in permanent teeth of periapical periodontitis.

The apical barrier technique in permanent teeth with extensive destruction of the periapical tissue and a long infection time is much more difficult to succeed, which is a clinical challenge. This study aimed to evaluate the long-term effects of iRoot BP Plus as an apical material in adult teeth. Fifty incisors and premolars were chosen for this study. All teeth were performed apical barrier with the same operator. After treatment, the teeth were clinically and radiographically evaluated at 1, 2 and 6 years. At the 1-year follow-up, 35 teeth had healed, and three patients developed an apical abscess due to root fracture at the 2-year follow-up. Six years postoperatively, one tooth showed root resorption, which was considered a failure. The long clinical evaluation confirmed that iRoot BP Plus is a suitable material for the apical barrier of mature teeth with open apices and periapical lesions.

Food Polyphenols in Radiation-Related Diseases: The Roles and Possible Mechanisms.

PURPOSE OF REVIEW: As science and technology continue to evolve, the potential harm of radiation to the human body cannot be overlooked. Radiation has the capacity to inflict cellular and body-wide damage. Polyphenols are a group of naturally occurring compounds that are found in an array of plant foods. Scientific studies have demonstrated that these compounds possess noteworthy anti-radiation efficacy. Furthermore, they have been observed to be less toxic at higher doses. In the present review, we discussed the mechanisms of ionizing radiation damage and the progress in the research on the radiation resistance mechanism of polyphenol compounds, to provide guidance for the prevention and treatment of radiation related diseases. RECENT FINDINGS: Food polyphenols can reduce the oxidative damage caused by ionizing radiation, clear free radicals, reduce DNA damage, regulate NF-KB, MAPK, JAK/STAT, Wnt and other signaling pathways, improve immune function, and have significant protective effects on radiation-induced inflammation, fibrosis, cancer and other aspects. In addition, it also has significant dual effects on radiation sensitization and radiation protection. Food polyphenols come from a wide range of sources, are abundant in daily food, and have no toxic side effects, demonstrating that food polyphenols have great advantages in preventing and treating radiation-related diseases.

Adaptive self-supervised learning for sequential recommendation.

Sequential recommendation typically utilizes deep neural networks to mine rich information in interaction sequences. However, existing methods often face the issue of insufficient interaction data. To alleviate the sparsity issue, self-supervised learning is introduced into sequential recommendation. Despite its effectiveness, we argue that current self-supervised learning-based (i.e., SSL-based) sequential recommendation models have the following limitations: (1) using only a single self-supervised learning method, either contrastive self-supervised learning or generative self-supervised learning. (2) employing a simple data augmentation strategy in either the graph structure domain or the node feature domain. We believe that they have not fully utilized the capabilities of both self-supervised methods and have not sufficiently explored the advantages of combining graph augmentation schemes. As a result, they often fail to learn better item representations. In light of this, we propose a novel multi-task sequential recommendation framework named Adaptive Self-supervised Learning for sequential Recommendation (ASLRec). Specifically, our framework combines contrastive and generative self-supervised learning methods adaptively, simultaneously applying different perturbations at both the graph topology and node feature levels. This approach constructs diverse augmented graph views and employs multiple loss functions (including contrastive loss, generative loss, mask loss, and prediction loss) for joint training. By encompassing the capabilities of various methods, our model learns item representations across different augmented graph views to achieve better performance and effectively mitigate interaction noise and sparsity. In addition, we add a small proportion of random uniform noise to item representations, making the item representations more uniform and mitigating the inherent popularity bias in interaction records. We conduct extensive experiments on three publicly available benchmark datasets to evaluate our model. The results demonstrate that our approach achieves state-of-the-art performance compared to 14 other competitive methods: the hit rate (HR) improved by over 14.39%, and the normalized discounted cumulative gain (NDCG) increased by over 18.67%.

Recent advances in developing modified C14 side chain pleuromutilins as novel antibacterial agents.

Owing to the increasing resistance to most existing antimicrobial drugs, research has shifted towards developing novel antimicrobial agents with mechanisms of action distinct from those of current clinical options. Pleuromutilins are antibiotics known for their distinct mechanism of action, inhibiting bacterial protein synthesis by binding to the peptidyl transferase center of the ribosome. Recent studies have revealed that pleuromutilin derivatives can disrupt bacterial cell membranes, thereby enhancing antibacterial efficacy. Both marketed pleuromutilin derivatives and those in clinical trials have been developed by structurally modifying the pleuromutilin C14 side chain to improve their antimicrobial activity. Therefore, this review aims to review advancement in the chemical structural characteristics, antibacterial activities, and structure-activity relationship studies of pleuromutilins, specifically focusing on modifications made to the C14 side chain in recent years. These findings provide a valuable reference for future research and development of pleuromutilins.