MSGNN-DTA: Multi-Scale Topological Feature Fusion Based on Graph Neural Networks for Drug-Target Binding Affinity Prediction.

The accurate prediction of drug-target binding affinity (DTA) is an essential step in drug discovery and drug repositioning. Although deep learning methods have been widely adopted for DTA prediction, the complexity of extracting drug and target protein features hampers the accuracy of these predictions. In this study, we propose a novel model for DTA prediction named MSGNN-DTA, which leverages a fused multi-scale topological feature approach based on graph neural networks (GNNs). To address the challenge of accurately extracting drug and target protein features, we introduce a gated skip-connection mechanism during the feature learning process to fuse multi-scale topological features, resulting in information-rich representations of drugs and proteins. Our approach constructs drug atom graphs, motif graphs, and weighted protein graphs to fully extract topological information and provide a comprehensive understanding of underlying molecular interactions from multiple perspectives. Experimental results on two benchmark datasets demonstrate that MSGNN-DTA outperforms the state-of-the-art models in all evaluation metrics, showcasing the effectiveness of the proposed approach. Moreover, the study conducts a case study based on already FDA-approved drugs in the DrugBank dataset to highlight the potential of the MSGNN-DTA framework in identifying drug candidates for specific targets, which could accelerate the process of virtual screening and drug repositioning.

A Nomogram for Predicting Surgical Timing in Neonates with Necrotizing Enterocolitis.

OBJECTIVE: To explore the surgical risk variables in patients with necrotizing enterocolitis (NEC) and develop a nomogram model for predicting the surgical intervention timing of NEC. METHODS: Infants diagnosed with NEC were enrolled in our study. We gathered information from clinical data, laboratory examinations, and radiological manifestations. Using LASSO (least absolute shrinkage and selection operator) regression analysis and multivariate logistic regression analysis, a clinical prediction model based on the logistic nomogram was developed. The performance of the nomogram model was evaluated using the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). RESULTS: A surgical intervention risk nomogram based on hypothermia, absent bowel sounds, WBC > 20 × 109/L or < 5 × 109/L, CRP > 50 mg/L, pneumatosis intestinalis, and ascites was practical, had a moderate predictive value (AUC > 0.8), improved calibration, and enhanced clinical benefit. CONCLUSIONS: This simple and reliable clinical prediction nomogram model can help physicians evaluate children with NEC in a fast and effective manner, enabling the early identification and diagnosis of children at risk for surgery. It offers clinical revolutionary value for the development of medical or surgical treatment plans for children with NEC.

Induction of Axillary Bud Swelling of Hevea brasiliensis to Regenerate Plants through Somatic Embryogenesis and Analysis of Genetic Stability.

To overcome rubber tree (RT) tissue culture explant source limitations, the current study aimed to establish a new Hevea brasiliensis somatic embryogenesis (SE) system, laying the technical foundation for the establishment of an axillary-bud-based seedling regeneration system. In this study, in vitro plantlets of Hevea brasiliensis Chinese Academy of Tropical Agricultural Sciences 917 (CATAS 917) were used as the experimental materials. Firstly, the optimum conditions for axillary bud swelling were studied; then, the effects of phenology, the swelling time of axillary buds (ABs), and medium of embryogenic callus induction were studied. Plantlets were obtained through somatic embryogenesis. Flow cytometry, inter-simple sequence repeat (ISSR molecular marker) and chromosome karyotype analysis were used to study the genetic stability of regenerated plants along with budding seedlings (BSs) and secondary somatic embryo seedlings (SSESs) as the control. The results show that the rubber tree's phenology period was mature, and the axillary bud induction rate was the highest in the 2 mg/L 6-benzyladenine (6-BA) medium (up to 85.83%). Later, 3-day-old swelling axillary buds were used as explants for callogenesis and somatic embryogenesis. The callus induction rate was optimum in MH (Medium in Hevea) + 1.5 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) + 1.5 mg/L 1-naphthalene acetic acid (NAA) + 1.5 mg/L Kinetin (KT) + 70 g/L sucrose (56.55%). The regenerated plants were obtained after the 175-day culture of explants through callus induction, embryogenic callus induction, somatic embryo development, and plant regeneration. Compared with the secondary somatic embryo seedling control, axillary bud regeneration plants (ABRPs) were normal diploid plants at the cellular and molecular level, with a variation rate of 7.74%.

Albumin-based near-infrared phototheranostics for frequency upconversion luminescence/photoacoustic dual-modal imaging-guided photothermal therapy.

Engineering versatile phototheranostics for multimodal diagnostic imaging and effective therapy has great potential in cancer treatment. However, developing an inherently versatile molecule is a huge challenge. In this work, a near-infrared organic dye (NRh) was synthesized and further bound with bovine serum albumin (BSA) to construct facile "one-for-all" phototheranostics (NRh-BSA NPs), which exhibited enhanced frequency upconversion luminescence (FUCL, λex/em = 850/825 nm) and excellent photoacoustic (PA) and photothermal properties (λ'ex = 808 nm). Additionally, the BSA-modified phototheranostics NRh-BSA NPs showed specific accumulation in the tumor region through passive targeting. Based on the FUCL/PA dual modal imaging-guidance, the NRh-BSA NPs not only can guarantee the accuracy of imaging of the U87MG tumor sites, but also can improve the therapeutic effect on ablating tumors without recurrence by photothermal therapy (PTT). Collectively, our work proposed a novel strategy to construct versatile phototheranostics with the unique FUCL/PA imaging-guided technique for accurate cancer theranostics.

Microbial community and soil enzyme activities driving microbial metabolic efficiency patterns in riparian soils of the Three Gorges Reservoir.

Riparian zones represent important transitional areas between aquatic and terrestrial ecosystems. Microbial metabolic efficiency and soil enzyme activities are important indicators of carbon cycling in the riparian zones. However, how soil properties and microbial communities regulate the microbial metabolic efficiency in these critical zones remains unclear. Thus, microbial taxa, enzyme activities, and metabolic efficiency were conducted in the riparian zones of the Three Gorges Reservoir (TGR). Microbial carbon use efficiency and microbial biomass carbon had a significant increasing trend along the TGR (from upstream to downstream); indicating higher carbon stock in the downstream, microbial metabolic quotient (qCO2) showed the opposite trend. Microbial community and co-occurrence network analysis revealed that although bacterial and fungal communities showed significant differences in composition, this phenomenon was not found in the number of major modules. Soil enzyme activities were significant predictors of microbial metabolic efficiency along the different riparian zones of the TGR and were significantly influenced by microbial α-diversity. The bacterial taxa Desulfobacterota, Nitrospirota and the fungal taxa Calcarisporiellomycota, Rozellomycota showed a significant positive correlation with qCO2. The shifts in key microbial taxa unclassified_k_Fungi in the fungi module #3 are highlighted as essential factors regulating the microbial metabolic efficiency. Structural equation modeling results also revealed that soil enzyme activities had a highly significant negative effect on microbial metabolism efficiency (bacteria, path coefficient = -0.63; fungi, path coefficient = -0.67).This work has an important impact on the prediction of carbon cycling in aquatic-terrestrial ecotones. Graphical abstract.

Effects of N and P additions on twig traits of wild apple (Malus sieversii) saplings.

BACKGROUND: Wild apple (Malus sieversii) is under second-class national protection in China and one of the lineal ancestors of cultivated apples worldwide. In recent decades, the natural habitation area of wild apple trees has been seriously declining, resulting in a lack of saplings and difficulty in population regeneration. Artificial near-natural breeding is crucial for protecting and restoring wild apple populations, and adding nitrogen (N) and phosphorous (P) is one of the important measures to improve the growth performance of saplings. In this study, field experiments using N (CK, N1, N2, and N3: 0, 10, 20, and 40 g m- 2 yr- 1, respectively), P (CK, P1, P2, and P3: 0, 2, 4, and 8 g m- 2 yr- 1, respectively), N20Px (CK, N2P1, N2P2, and N2P3: N20P2, N20P4 and N20P8 g m- 2 yr- 1, respectively), and NxP4 (CK, N1P2, N2P2, and N3P2: N10P4, N20P4, and N40P4 g m- 2 yr- 1, respectively) treatments (totaling 12 levels, including one CK) were conducted in four consecutive years. The twig traits (including four current-year stem, 10 leaf, and three ratio traits) and comprehensive growth performance of wild apple saplings were analyzed under different nutrient treatments. RESULTS: N addition had a significantly positive effect on stem length, basal diameter, leaf area, and leaf dry mass, whereas P addition had a significantly positive effect on stem length and basal diameter only. The combination of N and P (NxP4 and N20Px) treatments evidently promoted stem growth at moderate concentrations; however, the N20Px treatment showed a markedly negative effect at low concentrations and a positive effect at moderate and high concentrations. The ratio traits (leaf intensity, leaf area ratio, and leaf to stem mass ratio) decreased with the increase in nutrient concentration under each treatment. In the plant trait network, basal diameter, stem mass, and twig mass were tightly connected to other traits after nutrient treatments, indicating that stem traits play an important role in twig growth. The membership function revealed that the greatest comprehensive growth performance of saplings was achieved after N addition alone, followed by that under the NxP4 treatment (except for N40P4). CONCLUSIONS: Consequently, artificial nutrient treatments for four years significantly but differentially altered the growth status of wild apple saplings, and the use of appropriate N fertilizer promoted sapling growth. These results can provide scientific basis for the conservation and management of wild apple populations.

Coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome.

Diabetic nephropathy is a microvascular complication of diabetes mellitus, threatening the health of millions of people. Herein, we explored a blood glucose independent function of coptisine on diabetic nephropathy. A diabetic rat model was established by intraperitoneal administration of streptozotocin (65 mg/kg). Coptisine treatment (50 mg/kg/day) retarded body weight loss and reduced blood glucose. On the other hand, coptisine treatment also decreased kidney weight and the levels of urinary albumin, serum creatinine, and blood urea nitrogen, indicating an improvement of renal function. Treatment with coptisine also mitigated renal fibrosis, with alleviative collagen deposition. Likewise, in vitro study showed that coptisine treatment decreased apoptosis and fibrosis markers in HK-2 cells treated with high glucose. Furthermore, after coptisine treatment, the activation of NOD-like receptor pyrin domain containing protein 3 (NRLP3) inflammasome was repressed, with decreased levels of NLRP3, cleaved caspase-1, interleukin (IL)-1ß, and IL-18, indicating that the repression of NRLP3 inflammasome contributed to the effect of coptisine on diabetic nephropathy. In conclusion, this study revealed that coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome. It is indicated that coptisine may have the potential to be used in the diabetic nephropathy treatment.

Tailoring the Interface with a Multifunctional Ligand for Highly Efficient and Stable FAPbI3 Perovskite Solar Cells and Modules.

Perovskite solar cells (PeSCs) using FAPbI3 perovskite films often exhibit unfavorable phase transitions and defect-induced nonradiative interfacial recombination, resulting in considerable energy loss and impairing the performance of PeSCs in terms of efficiency, stability, and hysteresis. In this work, a facile interface engineering strategy to control the surface structure and energy-level alignment of perovskite films by tailoring the interface between the FAPbI3 film and hole-transporting layer using 4-hydroxypicolinic acid (4HPA) is reported. According to density functional theory studies, 4HPA has prominent electron delocalization distribution properties that enable it to anchor to the perovskite film surface and facilitate charge transfer at the interface. By enabling multiple bonding interactions with the perovskite layer, including hydrogen bonds, PbO, and PbN dative bonds, 4HPA passivation significantly reduces the trap density and efficiently suppresses nonradiative recombination. The obtained perovskite films exhibit superior optoelectronic properties with improved crystallinity, pure α-phase FAPbI3 , and favorable energy band bending. Following this strategy, 4HPA post-treatment PeSCs achieve a champion power conversion efficiency of 23.28% in 0.12 cm2 cells and 19.26% in 36 cm2 modules with excellent environmental and thermal stabilities.

Smartphone-Aided Fluorescence Detection of Cardiac Biomarker Myoglobin by a Ratiometric Fluorescent AuNCs-QDs Nanohybrids Probe with High Sensitivity.

Simple and sensitive detection of cardiac biomarkers is of great significance for early diagnosis and prevention of acute myocardial infarction (AMI). Here, a ratiometric fluorescent nanohybrids probe (AuNCs-QDs) was synthesized through the coupling of bovine serum albumin-functionalized gold nanoclusters (AuNCs) with CdSe/ZnS quantum dots (QDs) to realize simple and sensitive detection of cardiac biomarker myoglobin (Mb). The AuNCs-QDs probe shows pink fluorescence under UV light, with two emission peaks at 468 nm and 630 nm belonging to QDs and AuNCs, respectively. Importantly, the presence of Mb caused fluorescence quenching of the blue-emitting QDs, thereby inhibiting the fluorescence resonance energy transfer (FRET) process between QDs and AuNCs, and reducing the fluorescence intensity ratio (F468/F630) of AuNCs-QDs probe effectively. As the concentration of Mb increases, the ratiometric fluorescent probe also exhibits a visible fluorescence color change. The detection limit was as low as 4.99 µg/mL, and the response of the probe to Mb showed a good linear relationship up to 0.52 mg/mL. Moreover, the probe has excellent specificity for Mb. Besides, the AuNCs-QDs has been applied to detect Mb of urine samples. More importantly, we also developed an AuNCs-QDs probe modified smartphone-aided paper-based strip for on-site monitoring of Mb. As far as we know, this is the first report of a smartphone-aided paper-based strip for on-site quick monitoring of Mb, which provides a useful approach for AMI biomarker monitoring and may can be extended to other medical diagnostics.

Integrative Analysis of Core Genes and Biological Process Involved in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disordered disease, affecting the function of the ovaries in women of reproductive age. However, there are limited curative therapies for PCOS due to lack of reliable candidates. Hence, this study aimed to identify hub pathogenic genes and potential therapeutic targets for PCOS using bioinformatics tools. We obtained the expression profiles of 29 PCOS samples and 24 normal samples from three Gene Expression Omnibus (GEO) datasets. Then, the differentially expressed genes (DEGs) were screened, which were subjected to functional enrichment analyses. Moreover, we found 30 ferroptosis-related genes out of the 89 DEGs. Among the top 10 significant ferroptosis-related DEGs, 8 genes showed good predictive performance. We constructed interaction network of top three ferroptosis-related DEGs (SLC38A1, ACO1, DDIT3). Finally, real-time PCR was performed to test the relative expression of these genes. In conclusions, we have identified ferroptosis-related DEGs as core genes and potential therapeutic targets of PCOS based on comprehensive bioinformatics analysis. The findings are conducive to understanding of the pathogenesis of PCOS and paving the way towards curative therapies.

The asymmetrical ESR1 signaling in muscle progenitor cells determines the progression of adolescent idiopathic scoliosis.

Adolescent Idiopathic Scoliosis (AIS) is a common pediatric skeletal disease highly occurred in females. The pathogenesis of AIS has not been fully elucidated. Here, we reveal that ESR1 (Estrogen Receptor 1) expression declines in muscle stem/progenitor cells at the concave side of AIS patients. Furthermore, ESR1 is required for muscle stem/progenitor cell differentiation and disrupted ESR1 signaling leads to differentiation defects. The imbalance of ESR1 signaling in the para-spinal muscles induces scoliosis in mice, while reactivation of ESR1 signaling at the concave side by an FDA approved drug Raloxifene alleviates the curve progression. This work reveals that the asymmetric inactivation of ESR1 signaling is one of the causes of AIS. Reactivation of ESR1 signaling in para-spinal muscle by Raloxifene at the concave side could be a new strategy to treat AIS.

Determination of the coefficient of thermal expansion of ultra-low-expansion glass using an ultrasonic immersion testing method.

The coefficient of thermal expansion (CTE) of ultra-low-expansion (ULE) glass is critical to the development of precision optical systems. Herein, an ultrasonic immersion pulse-reflection method is proposed to characterize the CTE of ULE glass. The ultrasonic longitudinal wave velocity of ULE-glass samples with significantly different CTE values was measured using a correlation algorithm combined with moving-average filtering, which can achieve 0.2 m/s precision with a contribution to the ultrasonic CTE measurement uncertainty of 0.47 ppb/°C. Furthermore, the established ultrasonic CTE measurement model predicted the 5°C-35°C mean CTE with a root-mean-square error of 0.9 ppb/°C. Notably, a complete uncertainty analysis methodology was established in this paper, which can provide directional guidance for the subsequent development of higher-performance measurement devices and the improvement of relevant signal processing procedures.

hsa_circ_0051428 Facilitates the Progression of Thyroid Cancer by Sponging miR-1248 to Up-Regulate FN1.

Evidence displays that circular RNAs (circRNAs) are considerable mediators of numerous processes in cancer development. Given that many circRNAs are not functionally characterized, our aim was to explore the function and mechanisms of circ_0051428 in thyroid cancer (TC). The analysis of circ_0051428, miR-1248 and FN1 mRNA expression was conducted using real-time quantitative polymerase chain reaction. Cell growth was observed using CCK-8 and colony formation assays. Cell migration was investigated using wound healing assay. Cell apoptosis was identified by the expression of apoptosis-related proteins (Bax and Bcl-2) using Western blotting. Animal models were established to testify the role of circ_0051428 in vivo. The assumed binding between miR-1248 and circ_0051428 or FN1 was identified using dual-luciferase reporter or RIP assay. circ_0051428 exhibits an abnormally elevated expression in TC. circ_0051428 deficiency caused inhibition of TC cell proliferation, migration, clonogenic capacity, and inhibition of tumor growth in vivo. circ_0051428 directly targeted miR-1248, and FN1 was a target downstream of circ_0051428/miR-1248 axis. circ_0051428 could sponge miR-1248 to upregulate FN1. Furthermore, miR-1248 downregulation recovered circ_0051428 deficiency-suppressed cancer cell proliferation, survival and migration. Besides, the repressive effects of FN1 knockdown on cancer cell growth, survival and migration were also partly abolished by miR-1248 downregulation. circ_0051428 targeted miR-1248 to modulate FN1 expression, thereby facilitating the malignant progression of TC, which contributed to the understanding of the molecular mechanism of TC development.

Influence Factors and Feasibility Evaluation on Geological Sequestration of CO2 in Coal Seams: A Review.

The geological sequestration of CO2 in coal seams holds significant implications for coalbed methane development and greenhouse gas mitigation. This paper examines the principles, influencing factors, and evaluation methods for geological CO2 sequestration in coal seams by analyzing relevant domestic and international findings. Suitable geological conditions for CO2 sequestration include burial depths between 300 and 1300 m, permeability greater than 0.01 × 10-3 µm2, caprock and floor strata with water isolation capabilities, and high-rank bituminous coal or anthracite with low ash yield. Geological structures, shallow freshwater layers, and complex hydrological conditions should be avoided. Additionally, the engineering conditions of temperature, pressure, and storage time for CO2 sequestration should be given special attention. The feasibility evaluation of CO2 geological storage in coal seams necessitates a comprehensive understanding of coalfield geological factors. By integrating the evaluation principles of site selection feasibility, injection controllability, sequestration security, and development economy, various mathematical models and "one vote veto" power can optimize the sequestration area and provide recommendations for rational CO2 geological storage layout.

Electron transport chain inhibition increases cellular dependence on purine transport and salvage.

Cancer cells reprogram their metabolism to support cell growth and proliferation in harsh environments. While many studies have documented the importance of mitochondrial oxidative phosphorylation (OXPHOS) in tumor growth, some cancer cells experience conditions of reduced OXPHOS in vivo and induce alternative metabolic pathways to compensate. To assess how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts and plasma from patients with inborn errors of mitochondrial metabolism, and in cancer cells subjected to inhibition of the electron transport chain (ETC). All these analyses revealed extensive perturbations in purine-related metabolites; in non-small cell lung cancer (NSCLC) cells, ETC blockade led to purine metabolite accumulation arising from a reduced cytosolic NAD + /NADH ratio (NADH reductive stress). Stable isotope tracing demonstrated that ETC deficiency suppressed de novo purine nucleotide synthesis while enhancing purine salvage. Analysis of NSCLC patients infused with [U- 13 C]glucose revealed that tumors with markers of low oxidative mitochondrial metabolism exhibited high expression of the purine salvage enzyme HPRT1 and abundant levels of the HPRT1 product inosine monophosphate (IMP). ETC blockade also induced production of ribose-5' phosphate (R5P) by the pentose phosphate pathway (PPP) and import of purine nucleobases. Blocking either HPRT1 or nucleoside transporters sensitized cancer cells to ETC inhibition, and overexpressing nucleoside transporters was sufficient to drive growth of NSCLC xenografts. Collectively, this study mechanistically delineates how cells compensate for suppressed purine metabolism in response to ETC blockade, and uncovers a new metabolic vulnerability in tumors experiencing NADH excess.

E2EFP-MIL: End-to-end and high-generalizability weakly supervised deep convolutional network for lung cancer classification from whole slide image.

Efficient and accurate distinction of histopathological subtype of lung cancer is quite critical for the individualized treatment. So far, artificial intelligence techniques have been developed, whose performance yet remained debatable on more heterogenous data, hindering their clinical deployment. Here, we propose an end-to-end, well-generalized and data-efficient weakly supervised deep learning-based method. The method, end-to-end feature pyramid deep multi-instance learning model (E2EFP-MIL), contains an iterative sampling module, a trainable feature pyramid module and a robust feature aggregation module. E2EFP-MIL uses end-to-end learning to extract generalized morphological features automatically and identify discriminative histomorphological patterns. This method is trained with 1007 whole slide images (WSIs) of lung cancer from TCGA, with AUCs of 0.95-0.97 in test sets. We validated E2EFP-MIL in 5 real-world external heterogenous cohorts including nearly 1600 WSIs from both United States and China with AUCs of 0.94-0.97, and found that 100-200 training images are enough to achieve an AUC of >0.9. E2EFP-MIL overperforms multiple state-of-the-art MIL-based methods with high accuracy and low hardware requirements. Excellent and robust results prove generalizability and effectiveness of E2EFP-MIL in clinical practice. Our code is available at https://github.com/raycaohmu/E2EFP-MIL.

Application of tea polyphenols as additives in brown fermented milk: potential analysis of mitigating Maillard reaction products.

Brown fermented milk (BFM) is favored by consumers in the dairy market for its unique burnt flavor and brown color. However, Maillard reaction products (MRPs) from high temperature baking are also noteworthy. In this study, tea polyphenols (TP) were initially developed as potential inhibitors of MRPs formation in BFM. The results showed that the flavor profile of BFM did not change after adding 0.08% (wt/wt) of TP, and its inhibition rates on 5-hydroxymethyl-2-furaldehyde (5-HMF), glyoxal (GO), methylglyoxal (MGO), Nε-carboxymethyl lysine (CML) and Nε-carboxyethyl lysine (CEL) were 60.8%, 27.12%, 23.44%, 57.7% and 31.28%, respectively. After 21 d of storage, the levels of 5-HMF, GO, MGO, CML and CEL in BFM with TP were 46.3%, 9.7%, 20.6%, 5.2%, and 24.7% lower than the control group, respectively. Moreover, there was a smaller change in their color and the browning index was lower than that of the control group. The significance of this study was to develop TP as additives to inhibit the production of MRPs in brown fermented yogurt without changing color and flavors, thereby making dairy products safer for consumers.

Enhanced sulfamethoxazole photodegradation by N-SrTiO3/NH4V4O10 S-scheme photocatalyst: DFT calculation and photocatalytic mechanism insight.

In this study, we synthesized a N-SrTiO3/NH4V4O10 S-scheme photocatalyst by modifying NH4V4O10 nanosheets with various proportions of N-doped SrTiO3 nanoparticles using a mild hydrothermal method.Density Functional Theory(DFT) calculations were employed to elucidate thephotocatalytic mechanism, while the electron-hole transfer and separation of the S-type heterojunction were further characterized experimentally. The photocatalyst was applied to the photodegradation of sulfamethoxazole (SMX), a common water pollutant. Among all the prepared photocatalysts, 30 wt% N-SrTiO3/NH4V4O10 (NSN-30) displayed the highest photocatalytic performance. This was attributed to the facile electron transfer mechanism of the S-scheme heterojunction, which facilitated the effective separation of electron-holes and preserved the strong redox property of the catalyst. The possible intermediates anddegradation pathwaysin thephotocatalytic systemwere explored usingelectron paramagnetic resonance(EPR) and DFT calculations. Our findings demonstrate the potential of semiconductor catalysts to remove antibiotics from aqueous environments usinggreen energy.

Low-dose post-transplant cyclophosphamide with G-CSF/ATG based haploidentical protocol provides favorable outcomes for SAA patients.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT), as one of the life-saving treatments for severe aplastic anemia (SAA), is widely used because of its great donor availability. Over decades, granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocol (the so-called Beijing Protocol) has achieved favorable engraftment and survival outcomes. In this study, we modified the conventional Beijing Protocol: the full-dose Cyclophosphamide (Cy) (200 mg/kg in total) was divided into 42.75 mg/kg Cy on day -5 to day -2 and Low dose post-transplant Cy (PTCy) (14.5 mg/kg on days +3 and +4), hoping to reduce the incidence of severe acute graft-versus-host disease (aGVHD) and to guarantee successful and stable engraftment. Here we retrospectively reported and analyzed the data of first 17 patients with SAA who had received haplo-HSCT using this novel regimen between August 2020 and August 2022. The median follow-up was 522 days (range, 138-859 days). No patient developed primary graft failure. Four (23.5%) patients developed grade II bladder toxicity, two (11.8%) patients developed grade II cardiotoxicity. All patients achieved neutrophil and platelet engraftment at median times of 12 days (range, 11-20 days) and14 days (range, 8-36 days). During our follow-up, no patients developed grade III-IV aGVHD. The cumulative incidence of grade II and grade I aGVHD at 100 days was 23.5% (95% CI, 6.8%-49.9%) and 47.1% (95% CI, 23.0%-72.2%). Three patients (17.6%) developed chronic GVHD of skin, mouth, and eyes and all of which were mild. All patients are alive by the end of the follow-up, with a failure-free survival of 100%, which was defined as survival without treatment failures, such as death, graft failure, or relapse rate. The rate of cytomegalovirus (CMV) reactivation was 82.4% (95% CI, 64.3%-100%). The rate of Epstein-Barr virus (EBV) reactivation was 17.6% (95% CI, 3.8%-43.4%). No CMV disease and post-transplantation lymphoproliferative disorder (PTLD) occurred among these patients. In conclusion, the encouraging results of prolonged survival outcomes and reduced incidence of GVHD suggest promising effect of this novel regimen in haplo-HSCT for patients with SAA. Larger-sample prospective clinical trials are needed to confirm the effectiveness of this regimen.

Functional Characterization of a New Degradation Peptide BmTX4-P1 from Traditional Chinese Scorpion Medicinal Material.

Thermally processed Buthus martensii Karsch scorpion is an important traditional Chinese medical material that has been widely used to treat various diseases in China for over one thousand years. Our recent work showed that thermally processed Buthus martensii Karsch scorpions contain many degraded peptides; however, the pharmacological activities of these peptides remain to be studied. Here, a new degraded peptide, BmTX4-P1, was identified from processed Buthus martensii Karsch scorpions. Compared with the venom-derived wild-type toxin peptide BmTX4, BmTX4-P1 missed some amino acids at the N-terminal and C-terminal regions, while containing six conserved cysteine residues, which could be used to form disulfide bond-stabilized α-helical and ß-sheet motifs. Two methods (chemical synthesis and recombinant expression) were used to obtain the BmTX4-P1 peptide, named sBmTX4-P1 and rBmTX4-P1. Electrophysiological experimental results showed that sBmTX4-P1 and rBmTX4-P1 exhibited similar activities to inhibit the currents of hKv1.2 and hKv1.3 channels. In addition, the experimental electrophysiological results of recombinant mutant peptides of BmTX4-P1 indicated that the two residues of BmTX4-P1 (Lys22 and Tyr31) were the key residues for its potassium channel inhibitory activity. In addition to identifying a new degraded peptide, BmTX4-P1, from traditional Chinese scorpion medicinal material with high inhibitory activities against the hKv1.2 and hKv1.3 channels, this study also provided a useful method to obtain the detailed degraded peptides from processed Buthus martensii Karsch scorpions. Thus, the study laid a solid foundation for further research on the medicinal function of these degraded peptides.