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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) utilizing mismatched unrelated donors (MMUD) present a vital option for patients with hematologic malignancies without human leukocyte antigen (HLA)-matched donors. This multicenter retrospective study encompassed 211 adults with hematological malignancies receiving allo-HSCT with antithymocyte globulin (ATG) from ≥1 HLA locus MMUD. The findings revealed cumulative incidences of II-IV acute graft-versus-host disease (GVHD) at 180 days at 26.5%, and III-IV acute GVHD at 12.3%, with 3-year cumulative incidences for total and moderate-severe chronic GVHD at 37.0% and 21.0%. The 3-year non-relapse mortality (NRM) and relapse rates were 19.7% and 25.8%. The study reported a 3-year overall survival (OS) rate of 63.1%, a disease-free survival (DFS) rate of 54.5%, and a GVHD-free, relapse-free survival (GRFS) rate of 40.8%. Administration of a lower-dose ATG-Genzyme (ATG-G, ≤ 6 mg/kg) correlated with improved engraftment without significantly affecting survival, relapse, or viral reactivation rates. The quantity of HLA mismatches did not impact engraftment, GVHD, viral reactivation, OS, DFS, GRFS, relapse, or NRM. In conclusion, MMUD allo-HSCT with ATG demonstrates favorable outcomes for patients with hematological malignancies, with no evident correlation between the degree of mismatch and post-transplantation results. Utilizing a lower dose of ATG-G ( ≤ 6 mg/kg) proved efficacious, delivering comparable clinical advantage., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: This study aims to identify clinical laboratory parameters for the diagnosis of newly diagnosed multiple myeloma (NDMM), establish optimal cutoffs for early screening, and develop a diagnostic model for precise diagnosis., Methods: The study conducted a retrospective analysis of 279 NDMM patients and 553 healthy subjects at Zhejiang Province People's Hospital between January 2008 and June 2023. Multifactor LR was employed to explore clinical laboratory indicators with diagnostic value for NDMM, determine optimal cutoff values and contract a diagnostic model. The diagnostic efficacy and clinical utility were evaluated using receiver operating characteristic curves (ROC), sensitivity, specificity, and other indicators., Results: Multifactor analysis revealed that hemoglobin (Hb), albumin (Alb), and platelet distribution width (PDW) were significant diagnostic factors for NDMM. Optimal cutoff values for Hb, Alb, and PDW in MM diagnosis were determined, and the results showed a significant increase in the probability of NDMM diagnosis when Alb was below 39.3 g/L, Hb was below 11.6 g/dL, and PDW was below 14.1 fL. The diagnostic model constructed from the development cohort demonstrated a high area under the ROC curve of 0.960 (95% CI 0.942-0.978) and exhibited good sensitivity (0.860), specificity (0.957). The area under the curve (AUC) value of the diagnostic model in the external validation cohort was 0.979, confirming its good diagnostic efficacy and generalization., Conclusions: The optimal cutoff values for Hb, Alb, and PDW and the diagnostic model designed in the study provided good accuracy and sensitivity for the initial screening and diagnosis of NDMM., (© 2024. The Author(s).)

Background: Although the prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has improved with the introduction of tyrosine kinase inhibitors (TKIs) and stem cell transplantation, prevention of relapse after transplantation remains a concern. The aim of this study was to compare the impact of TKI prophylaxis with imatinib and dasatinib on long-term outcomes after transplantation., Methods: Patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) and received TKI prophylaxis after allo-HSCT were included in this retrospective analysis. Two cohorts were established based on the choice of TKI prophylaxis: the imatinib (Ima) and dasatinib (Das) cohorts. The survival and safety outcomes of these cohorts were compared., Results: Ninety-one patients in the Ima cohort and 50 in the Das cohort were included. After a median follow-up of 50.6 months, the 5-year cumulative incidence of relapse, nonrelapse mortality rate, and overall survival in the Ima and Das cohorts were 16.1% and 12.5%, 5.2% and 9.8%, and 86.5% and 77.6%, respectively, with no statistical differences. The cumulative incidence of mild chronic graft-versus-host disease was higher in the Das cohort. The most common adverse event was neutropenia (64.7% vs. 69.5%). The Das cohort had a higher incidence of gastrointestinal bleeding (25.5% vs. 2.3%) and gastrointestinal reaction (48.9% vs. 31.4%) than the Ima cohort. The proportion of patients treated on schedule was significantly lower in the Das cohort than in the Ima cohort, and drug intolerance was the main reason for protocol violation., Conclusions: For patients with Ph+ ALL undergoing allo-HSCT in CR1, imatinib prophylaxis achieved long-term outcomes similar to those of dasatinib., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Bloodstream infection (BSI) represent a prevalent complication in haematological malignancies (HMs). Typically, Patients with BSI usually undergo empirical treatment pending pathogen identification. The timely and effective management of BSIs significantly influences patient prognosis. However, pathogen distribution in BSIs exhibits regional variation. In this study, we investigated the clinical characteristics, pathogen spectrum, drug resistance, risk factors of short-term prognosis and long-term prognostic factors of acute myeloid leukemia (AML) patients with BSI at Zhejiang Provincal People's Hospital., Methods: From 2019 to 2021, a total of 56 AML patients with BSI were treated in the Department of Haematology at Zhejiang Province People's Hospital. Data regarding pathogen spectrum and drug resistance were collected for analysis. The patients were stratified into non-survivor cohort and survivor cohort within 30 days after BSI, and the predictors of 30-days mortality were identified through both univariate and multivariate Logistic regression analyses. Furthermore, Kaplan-Meier survival analysis and Cox regression analysis were employed to ascertain the risk factors associated with poor prognosis in AML patients complicated by BSI., Results: A total of 70 strains of pathogenic bacteria were isolated from 56 AML patients with BSI. Gram-negative bacteria constituted the predominant pathogens (71.4%), with Klebsiella pneumoniae being the most prevalent (22.9%). Gram-positive bacteria and fungi accounted for 22.9% and 5.7%, respectively. Univariate and multivariate analyses revealed significant differences in total protein, albumin levels, and the presence of septic shock between the non-survivor cohort and the survior cohort 30 days post-BSI. COX regression analysis showed that agranulocytosis duration exceeding 20 days (HR:3.854; 95% CI: 1.451-10.242) and septic shock (HR:3.788; 95% CI: 1.729-8.299) were independent risk factors for poor prognosis in AML patients complicated by BSI. Notably, the mortality rate within 30 days after Stenotrophomonas maltophilia infection was up to 71.4%., Conclusions: In this study, Gram-negative bacteria, predominantly Klebsiella pneumoniae, constituted the primary pathogens among AML patients with BSIs. Serum albumin levels and the presence of septic shock emerged as independent risk factors for mortality within 30 days among AML patients with BSI. In terms of long-term prognosis, extended agranulocytosis duration exceeding 20 days and septic shock were associated with elevated mortality rates in AML patients with BSI. Additionally, in our centre, Stenotrophomonas maltophilia infection was found to be associated with a poor prognosis. Early intervention for Stenotrophomonas maltophilia infection in our centre could potentially improve patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Li, Shou, Shi, Song, Hu, Wang, Chen and Tong.)

Cervical cancer (CC) is a growing health concern, emphasizing the need for reliable biomarkers in treatment selection and prognosis assessment. We analyzed gene expression profiles and clinicopathological data from The Cancer Genome Atlas (TCGA) for CC. Using Consensus Cluster Plus, we applied machine learning to cluster the CC cohort. Differential analysis was performed using the edge R package, while weighted correlation network analysis (WGCNA) was conducted using the WGCNA package. Single-sample gene set enrichment analysis (ssGSEA) evaluated immune cell abundance and computed the m6Ascore. Western blot and Q-PCR validated the m6A score in CC. Common copy number variation alterations were observed in the 23 m6A-related genes in CC, and their mutation frequency was summarized in a waterfall chart. Patients were grouped into two clusters, m6AclusterA and m6AclusterB. Improved clinical outcomes were observed in m6AclusterA, while m6AclusterB exhibited higher infiltration of 14 immune cell types. WGCNA analysis generated seven integrated modules, enriched in several biological processes. Prognostic differential genes were used to generate two gene clusters (gene Cluster I and gene Cluster II). Using ssGSEA, the m6Ascore was calculated for each patient. Lower m6Ascore correlated with better clinical outcomes, lower gene mutation frequency, and wild-type status. We investigated the sensitivity of high and low m6Ascore to immunotherapy, visualized through violin and UMAP diagrams showcasing crosstalk among single-cell clusters. The key gene PFKFB4 showed higher expression in CC cell lines and tumor tissues compared to normal cells and tissue. Our study elucidates the role of m6A molecules in predicting prognosis, biological features, and appropriate treatment for CC patients.

Proteins and peptides can assemble into functional amyloid fibrils with distinct architectures. These amyloid fibrils can fulfil various biological functions in living organisms, and then be degraded. By incorporating an amyloidogenic segment and enzyme-cleavage segment together, we designed a peptide (enzyme-cleavage amyloid peptides (EAP))-based functional fibril which could be degraded specifically by gelatinase. To gain molecular insights into the assembly and degradation of EAP fibrils, we determined the atomic structure of the EAP fibril using cryo-electron microscopy. The amyloidogenic segment of EAP adopted a β-strand conformation and mediated EAP-fibril formation mainly via steric zipper-like interactions. The enzyme-cleavage segment was partially involved in self-assembly, but also exhibited high flexibility in the fibril structure, with accessibility to gelatinase binding and degradation. Moreover, we applied the EAP fibril as a tunable scaffold for developing degradable self-assembled antimicrobial fibrils (SANs) by integrating melittin and EAP together. SANs exhibited superior activity for killing bacteria, and significantly improved the stability and biocompatibility of melittin. SANs were eliminated automatically by the gelatinase secreted from targeted bacteria. Our work provides a new strategy for rational design of functional fibrils with a feedback regulatory loop for optimizing the biocompatibility and biosafety of designed fibrils. Our work may aid further developments of "smart" peptide-based biomaterials for biomedical applications., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Piezoelectric polymer nanofibers are attracting increasing attention in the stimulation of cell growth and proliferation in tissue engineering and wound healing applications. However, their intrinsic non-biodegradability in vivo hinders widespread applications in the biological fields. Herein, we designed, synthesized and characterized composite materials of silk fibroin (SF)/LiNbO 3 (LN) nanoparticles/MWCNTs by electrospinning technology, which displayed good biocompatibility and comparable piezoelectric properties with an output current of up to 15 nA and output voltage of up to 0.6 V under pressure stimulation, remaining stable after 200 cycles of pressure release without significant decay. Meanwhile, the mechanical properties of the LN/CNTs/SF-nanofiber scaffolds (SF-NFSs) are also enhanced, with a tensile strength reaching 12.84 MPa and an elongation at break reaching 80.07%. Importantly, in vitro cell proliferation experiments showed that the LN/CNTs/SF-NFSs promoted cell proliferation at a rate of 43%. Accordingly, the mouse wound healing experiments further indicated that they could accelerate the healing of skin wounds in mice that were continuously moving. Therefore, SF-based piezoelectric nanofibrous scaffolds exhibit potential for use in rapid wound healing and this sheds light on smart treatment for tissue engineering in biomedicine.

It is imperative to develop an antibiotic-free and long-term effective strategy for treating chronic wound infections due to the long-term utilization of antibiotics easily causing drug resistance. Herein, we fabricated a novel poly-N-isopropylacrylamide (PNIPAM)/polyacrylamide (PAM) coupling thermosensitive hydrogel integrating 1D lysozyme nanofiber doped with CuS nanoparticles (CuS/PP) and loading antibacterial peptide melittin (M) (CuS/PP-M) for combating chronic wound infection via photothermal modulating the release of melittin. For the CuS/PP-M hydrogel, the copolymerization of PNIPAM and PAM allows the lower critical solution temperature (LCST) higher than the body temperature, effectively hindering the spontaneous release of melittin when contacts the infected wound, while the integration of LNF/CuS nanofibers provides a stable photothermal treatment for triggering the release of melittin. As a result, the CuS/PP-M hydrogel exhibits synergistically enhanced effect on killing both Gram-positive and Gram-negative bacteria, which maintains more than 99 % bactericidal efficiency, even displays a long-term and multiply antibacterial performance by photothermal modulating melittin release. Moreover, the CuS/PP-M hydrogel presents both high antibacterial activity and excellent wound healing performance in the mouse wound model, thereby benefiting the chronic wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Acute myeloid leukemia (AML) is an aggressive hematologic cancer in adults. Some patients exhibit restricted T cell infiltration and do not respond to routine treatments. This may be prevented by enhancing adaptive immunity by stimulating innate immune cells inside the tumor microenvironment (TME). To activate the adaptive immunological reaction against tumors, type I interferons (IFNs) can promote the presentation of tumor-specific cytotoxic T lymphocyte (CTL) cell recruitment. During the activation of innate immunity, cyclic di-nucleotides (CDNs) bind to and stimulate the stimulator of interferon genes (STING), a protein localized inside the endoplasmic reticulum (ER) membrane, resulting in the expression of type I IFNs. The efficacy of STING agonists as effective stimulators of the anti-tumor response in AML is being investigated in numerous clinical studies. Therefore, the purpose of this investigation was to thoroughly review existing knowledge in this field and provide perspective into the clinical potential of STING agonists in AML., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

The fast monitoring of oral bacterial infection, bacterial clearance and repairing of enamel damage caused by dental caries relies on an effective way of monitoring, killing and repairing in situ , but presents a major challenge in oral healthcare. Herein, we developed a bio-inspired versatile free-standing membrane by filling TiO 2 nanotube arrays with β-sheet-rich silk fibroin and cleaving them from Ti foil, as inspired by nacre or enamel-like structures. The robust transparent membrane exhibited good mechanical properties, and could indicate acid-base microenvironment variation and the infection of S. mutans in a 5 min test by loading cyanidin cations in the membrane. Meanwhile, it can be used for photocatalysis and nanoreservoirs ascribed to TiO 2 nanotubes, to kill and remove 99% of S. mutans bacteria under interval UV irradiation with low-power density, and load functional peptide to induce the remineralization on the etched-enamel for long-term treatment, tested in vitro and in vivo . The mechanical property of repaired enamel is improved in comparison. This bio-inspired constructed membrane would be applied in the prevention and treatment of oral cavity related diseases, such as enamel demineralization and dental caries, etc.

Hemostasis and anti-infection are crucial for emergency treatment of severe trauma. Developing functional biomaterial with efficient hemostasis, antibacterial activity and wound healing is of great social significance and clinical value to fast stop bleeding and save lives, but it is still challenged. Here we designed a series of multifunctionalized SA/PDA cryogels by using two-step cross-linking of dopamine and sodium alginate. The resulting interpenetrating network structure had good swelling ratio, excellent mechanical and shape memory properties. Compared with cotton gauze and gelatin sponge, the cryogels exhibited excellent activation of coagulation cascade, more blood cells and platelet adhesion. Due to the action of polydopamine, the cryogel also showed good antioxidant activity and photothermal antibacterial ability assisted by near-infrared radiation, as well as better wound healing performance than gelatin sponge and Tegaderm™ film. Moreover, in the tests of mouse tail docking model, rat femoral artery hemostasis model and non-compressible rabbit liver defect model, the treatment by SA/PDA cryogels presented less blood loss and shorter hemostasis time than cotton gauze and gelatin sponge. Therefore, SA/PDA cryogels with simple preparation process, low cost, and good biocompatibility would be applied in the variety of great clinical applications in bleeding control, anti-infection and wound healing, etc., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The relationship between standardized serum 25-hydroxyvitamin D (25(OH)D) concentration and incident anemia in the United States (U.S.) is unclear. The purpose of our study was to examine the association between serum 25(OH)D and anemia risk. We performed a cross-sectional analysis of the U.S. population participating in the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. A generalized linear model and restricted cubic spline (RCS) plot curve were constructed to assess the relationship between serum 25(OH)D concentration and anemia incidence. Additionally, the association between serum 25(OH)D concentration and red blood cell (RBC) count and hemoglobin (HB) levels was investigated using generalized additive models with smooth functions. Subgroup analysis also was performed. A total of 29933 individuals were included in our research. After adjusting for known confounding variables, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) for association of serum 25(OH)D with anemia across the second, third, and fourth quartiles were 0.735 (0.651, 0.829), 0.527 (0.461, 0.602), and 0.696 (0.611, 0.792), respectively. Serum 25(OH)D concentration was associated with anemia risk in a U-shaped pattern, as shown by an RCS plot ( P for nonlinearity <0.001). In addition, RBC count and Hb levels initially increased and then decreased as serum 25(OH)D levels increased. Serum 25(OH)D concentration and risk of anemia are associated with a U-shaped curve in the U.S. general population. Serum 25(OH)D concentration in the range 59.7-70.3 nmol/l was associated with anemia incidence <1. Therefore, the risk of anemia can be reduced by close monitoring and appropriate vitamin D supplementation., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yang Zhang et al.)

With the revelation of the close link between Alzheimer's disease (AD) and type II diabetes (T2D) and the possible assembly of multiple amyloid peptides therein, it is critical to understand and regulate the co-fibrillation pathway between related amyloid peptides. Here, we show experimentally and theoretically that electric field (EF) inhibited hybrid amyloid fibrillation of β-amyloid peptide (Aβ) and human islet amyloid peptide (hIAPP) by modulating the hetero-aggregation pathway. Experimental results confirm that the β-sheet secondary structure of amyloid peptides would be disrupted under small static EF and accompanied by transforming fibril aggregates into amorphous particles in vitro. Molecular dynamics simulations further demonstrate that even with the transformation of the secondary structure from β-sheet to random coil, the strong interaction between Aβ and hIAPP peptides would remain largely unaffected under the small static EF, leading to the formation of amorphous nanoparticles observed in the experiments. This inhibitory effect of EF on the co-fibrillation of multiple amyloid peptides might contribute to reducing the mutual deterioration of different degenerative diseases and show great potential for the noninvasive treatment of amyloid-related diseases.

Objective: Considering the role of lncRNAs reported as regulators in acute myeloid leukemia (AML) progression, the current research aims to investigate the role of PAX8-AS1 in chemo-resistant AML., Methods: Human AML cells HL60 and human doxorubicin (ADM)-resistant AML cells (HL60/ADM cells) were used to establish in vitro models of chemo-sensitive AML and refractory/recurrent AML, respectively. CCK-8 assay and flow cytometry were used to determine cell resistance to ADM, viability, and apoptosis. PAX8-AS1, miR-378g, and ERBB2 expressions in the models and/or AML patients were quantified via qRT-PCR or Western blot. The miRNA/mRNA axis targeted by PAX8-AS1 was analyzed using Starbase, TargetScan, or GEO and validated through a dual-luciferase reporter assay. The expressions of Bcl-2, Bax, and C Caspase-3 in cells were quantitated by Western blot., Results: The highly expressed PAX8-AS1 was observed in AML patients and HL60 cells, which was more evident in refractory/recurrent AML patients and HL60/ADM cells. Compared with that in ADM-treated parental HL60 cells, the viability of ADM-treated HL60/ADM cells remained strong. PAX8-AS1 overexpression increased viability and Bcl-2 expression, while diminishing apoptosis, Bax, and C Caspase-3 expressions in HL60 cells. However, the abovementioned aspects were oppositely impacted by PAX8-AS1 silencing in HL60/ADM cells. PAX8-AS1 directly targeted miR-378g, whose expression pattern is opposite to that of PAX8-AS1 in AML. MiR-378g upregulation abrogated the effects of PAX8-AS1 overexpression on HL60 cells. MiR-378g downregulation offset PAX8-AS1 silencing-induced effects on HL60/ADM cells. Moreover, ERBB2 was recognized as the target of miR-378g, with a higher expression in HL60/ADM cells than in HL60 cells., Conclusion: PAX8-AS1 silencing decreases cell viability, enhances apoptosis, and suppresses ADM resistance in AML via regulating the miR-378g/ERBB2 axis., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Xiaolu Song et al.)

Herein, we have verified the interaction between the functional peptides from the SARS-CoV-2 and cell membrane, and we further proved that peptides exhibit little membrane disruption. The specific amino acids (Lys, Ile, Glu, Asn, Gln, etc.) with charge or hydrophobic residues play a significant role during the functional-peptide binding to membrane. The findings could provide the hints related to viral infection and also might pave the way for development of new materials based on peptides with membrane-binding activity, which would enable functional peptides further as peptide adjuvants, in order to help deliver the cancer drug into tumor cells for the efficient tumor therapy.

As mimics of the extracellular matrix, surfaces with the capability of capturing and releasing specific cells in a smart and controllable way play an important role in bacterial isolation. In this work, we fabricated a dual-responsive smart biointerface via peptide self-assembly and reversible covalent chemistry biomimetic adhesion behavior for bacterial isolation. Compared with that of the biointerface based on a single reversible covalent bond, the bacterial enrichment efficiency obtained in this work was 2.3 times higher. Furthermore, the release of bacteria from the surface could be achieved by dual responsiveness (sugar and enzyme), which makes the biointerface more adaptable and compatible under different conditions. Finally, the reusability of the biointerface was verified via peptide self-assembly and the regenerated smart biointerface still showed good bacterial capture stability and excellent release efficiency, which was highly anticipated to be more widely applied in biomaterial science and biomedicine in the future.

The linear polarized (LP) mode multiplexer based on the inverse designed multi-plane light conversion (MPLC) has the advantages of low insertion loss and low mode crosstalk. However, the multiplexer also requires the fabrication and alignment accuracy in experiments, which have not been systematically analyzed. Here, we perform the error tolerance analysis of the MPLC and summarize the design rules for the LP mode multiplexer/demultiplexer. The error tolerances in the fabrication process and experimental demonstration are greatly released with proper parameters of the input/output optical beam waist, the pitch of optical beam array, and the propagation distances between the phase plane. To proof this design rule, we experimentally demonstrate the LP mode multiplexer generating LP01, LP11a, LP11b, LP21 modes and coupling to the few mode fiber, with the insertion loss lower than -5 dB. The LP modes are demultiplexed by MPLC, with the crosstalk of different mode groups lower than -10 dB. LP modes carrying 10 Gbit/s on-off keying signals transmit in a 5 km few mode fiber. The measured bit error rates (BER) curves of the LP01, LP11a, LP21 modes have the power penalties lower than 12 dB.

Herein we reported a versatile dynamic biointerface based on pH-responsive peptide self-assembly and disassembly to capture the bacteria to avoid bacteria further infected tissue around that can release peptides from the surface in a slightly acidic environment to kill the bacteria with the specificity. The exposed biointerface still presented infection resistance.

BACKGROUND Infections are the main cause of mortality and morbidity in multiple myeloma (MM) patients. However, adult immunodeficiency specialists in China are lacking, and the care of secondary immunodeficiency (SID) and the prognostic role of hypogammaglobulinemia in MM is unknown. MATERIAL AND METHODS MM patients (295) were retrospectively analyzed between January 2012 and 2020 in Zhejiang Provincial People's Hospital, Hangzhou Medical College. MM patients with immunoglobulin (Ig) G <5 g/L were defined as SID patients. The care of these patients and the prognostic role of IgG <5 g/L were analyzed RESULTS Forty-five of 295 MM patients with IgG <5 g/L were defined as SID patients. These 45 patients mainly had recurrent infections, especially pulmonary bacterial infections; 2 patients had them 5 times/year. The median survival time was significantly shorter in MM patients with SID (24 vs 66 months). More importantly, the multivariate and univariate analysis revealed that IgG <5 g/L was an independent prognostic factor for MM patients. CONCLUSIONS Ig replacement therapy or prophylactic antibiotics for MM patients with SID were lacking in this single retrospective study. IgG <5 g/L could be a prognostic marker for MM patients.

The scaffold materials with good mechanical and structural properties, controlled drug release performance, biocompatibility and biodegradability are important tenet in tissue engineering. In this work, the functional core-shell nanofibers with poly(ε-caprolactone) (PCL) as shell and silk fibroin heavy chain (H-fibroin) as core were constructed by emulsion electrospinning. The transmission electron microscopy confirmed that the nanofiber with core-shell structure were successfully prepared. The constructed nanofiber materials were characterized by the several characterization methods. The results showed that ethanol treatment could induce the formation of β-sheet of H-fibroin in composite nanofibers, thus improving the mechanical properties of PCL/H-fibroin nanofiber scaffold. In addition, we evaluated the potential of PCL/H-fibroin nanofiber membrane as a biological scaffold. It was found that PCL/H-fibroin nanofiber scaffold was more conducive to cell adhesion and proliferation with the increment of H-fibroin. Finally, in vitro drug release presented that PCL/H-fibroin core-shell nanofibers could effectively reduce the prophase burst of drug molecules and show the sustained drug release. The PCL/H-fibroin nanofiber scaffolds constructed in this work have good mechanical properties, biocompatibility, and display good potential in biomedical applications, such as drug carriers, tissue engineering and wound dressings, etc., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: Interaction with bone marrow stromal cells (BMSCs) has been suggested as an important mechanism for the progression of multiple myeloma (MM) cells, while exosomes are crucial mediators for cell-to-cell communication. The study was to investigate the miRNA profile changes in exosomes released by BMSCs of MM patients and explore their possible function roles.The microarray datasets of exosomal miRNAs in BMSCs were downloaded from the Gene Expression Omnibus database (GSE110271: 6 MM patients, 2 healthy donors; GSE78865: 4 donors and 2 MM patients; GSE39571: 7 MM patients and 4 controls). The differentially expressed miRNAs (DEMs) were identified using the LIMMA method. The target genes of DEMs were predicted by the miRwalk 2.0 database and the hub genes were screened by constructing the protein-protein interaction (PPI) network, module analysis and overlapping with the differentially expressed genes (DEGs) after overexpression or knockout of miRNAs.Three downregulated DEMs were found to distinguish MM from normal and MM-MGUS controls in the GSE39571 dataset; one downregulated and one upregulated DEMs (hsa-miR-10a) could differentiate MM from normal and MM-MGUS controls in the GSE110271-GSE78865 merged dataset. Furthermore, 11 downregulated (hsa-miR-16) and 1 upregulated DEMs were shared between GSE39571 and merged dataset when comparing MM with normal samples. The target genes were predicted for these 17 DEMs. PPI with module analysis showed IGF1R and CCND1 were hub genes and regulated by hsa-miR-16. Furthermore, EPHA8 was identified as a DEG that was downregulated in MM cells when the use of has-miR-10a mimics; while IGF1R, CCND1, CUL3, and ELAVL1 were also screened as DEGs that were upregulated in MM cells when silencing of hsa-miR-16.BMSCs-derived exosomal miR-10a and miR-16 may be involved in MM progression by regulating EPHA8 or IGF1R/CCND1/CUL3/ELAVL1, respectively. These exosomal miRNAs or genes may represent potential biomarkers for diagnosis of MM and prediction of progression and targets for developing therapeutic drugs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Unlike Western countries, there are still few clinical immunology specialists in China, and the optimal care for secondary immunodeficiency caused by hematological malignancies is unknown. Therefore, we initiated this clinician survey study to describe the current situation of the care for malignancy patients with hypogammaglobulinemia in China.We adapted a previously published online questionnaire of current clinical practices regarding the management of secondary immunodeficiency caused by hematological malignancies and then distributed the questionnaire to 52 hematologists in China via WeChat mobile software; the survey collected demographic details, starting dosage, target immunoglobulin (Ig) level, monitoring, criteria for stopping Ig replacement, vaccination use, and oral antibiotic prophylaxis for hypogammaglobulinemia patients.Forty-eight hematologists responded. 28(58.33%) respondents had more than 10 years of experience. Nevertheless, 40(83.33%) respondents reported that they did not use any specific criteria for prophylactic Ig replacement in hypogammaglobulinemia patients. However, 27(56.25%) respondents reported that they had used intravenous immunoglobulin (IVIG); however, the starting dose, frequency, and target Ig level were significantly varied. Additionally, the criteria for stopping Ig replacement were significantly varied. Only one respondent (2.08%) used subcutaneous immunoglobulin (SCIG). Moreover, 35(72.92%) respondents reported no vaccination prior to Ig replacement, and 47(97.92%) respondents reported that they had not used antibiotic prophylaxis in secondary hypogammaglobulinemia patients.Official guideline for the care for secondary immunodeficiency (SID) of the hematological malignancies patients should be issued in China, and significant attention of the hematologists should be paid to the use of prophylactic antibiotics and Ig replacement for the care of patients with hypogammaglobulinemia caused by hematological malignancies, as these agents could significantly reduce the infection rate in China., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Candida tropicalis is the most common non-albicans Candida species identified in immunocompromised patients, which often appears with high mortality. However, data on the outcomes of treatment for Candida tropicalis fungemia in patients with neutropenia remain limited., Methods: In the present study, 90 neutropenic adult patients with proven Candida tropicalis fungemia, who received initial antifungal therapy, were retrospectively analyzed., Results: These results revealed that the overall 8-day and 30-day mortality among patients in the entire data set were 22.2% and 33.3%, respectively. However, there was no significant difference between the survival and death group, in terms of baseline characteristics. The univariate analysis of risk factors identified the treatment with azole as a predictor of mortality, while treatments that containing amphotericin B were associated with reduced mortality. In addition, the survival rate on day 30 was observed in 60.7% (17/28) of patients who were initially treated with echinocandins, while this was observed in 86.4% (19/22, P= 0.039) and 100% (13/13, P= 0.024) of patients treated with amphotericin B plus echinocandins and amphotericin B, respectively., Conclusion: These data indicate for the first time that the initial therapy with amphotericin B-based agents was associated with a better survival rate and could be assessed as the optimal strategy for the treatment of Candida tropicalis fungemia in patients with neutropenia., Competing Interests: The authors declare that they have no competing interests., (© 2020 You et al.)

Problem: Quercetin has been shown to display intensive antioxidant activity against ROS-mediated damage in chilled semen, and the effects and molecular mechanisms of Quercetin on sperm function in the infertile patients with leukocytospermia remain largely unknown., Methods: Semen samples were collected from the infertile men with leukocytospermia (n = 56) and fertile men (n = 44). Computer-assisted semen analysis (CASA) was used to determine sperm motility before and after Quercetin incubation (10 μmol/L). Changes in H 2 O 2 , sperm mitochondrial DNA (mtDNA), cytochrome B (Cty B), and NADH dehydrogenase 5 (NADH5) contents were measured. Furthermore, hyperactivated motility (HA) and acrosome reaction rates were detected after the stimulation by progesterone with or without Quercetin, respectively., Results: Quercetin could significantly improve sperm motility from the leukocytospermic patients. The level of H 2 O 2 was significantly decreased in the supernatant of leukocytospermic patients after Quercetin treatment. The content of mtDNA in sperm was significantly decreased, whereas the contents of Cyt B and NADH 5 in sperm were significantly increased. Sperm hyperactivated motility and acrosome reaction induced by progesterone were enhanced by Quercetin in sperm from the infertile men with leukocytospermia., Conclusion: These data indicate Quercetin could display protective effects against oxidative damage on sperm from the infertile men with leukocytospermia., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The catalytic activity of iron(II) complexes with functionalized amine-pyrazolyl tripodal ligands toward dimerization of terminal alkynes in the presence a base (KO t Bu or NaO t Bu) has been studied. An unusual E / Z selectivity of the reaction determined by tert -butoxide was observed., Competing Interests: The authors declare no competing financial interest.

Background/aim: As the knowledgebase of acute myeloid leukemia (AML) has grown, classification systems have moved to incorporate these new findings., Methods: We assessed 32,941 patients with AML whose records are contained in the Surveillance, Epidemiology, and End Results (SEER) database., Results: Half of all patients diagnosed between 2001 and 2013 did not have a World Health Organization (WHO) classification. Acute promyelocytic leukemia and acute panmyelosis with myelofibrosis were associated with the longest leukemia-specific survival (110 and 115 months, respectively), and AML with minimal differentiation and acute megakaryoblastic leukemia with the shortest (30 and 28 months, respectively). For patients in the WHO groups AML not otherwise specified (AML-NOS) and AML with recurrent genetic abnormalities (AML-RGA), the risk of death was greater for older patients and less for married patients. Black patients with any type of AML-NOS also had a higher risk of death. Patients whose case of AML did not receive a WHO classification were older and this group had a higher risk of death when compared to patients with a WHO type of AML-NOS., Conclusion: Our findings highlight the divergent outcomes of patients with AML and the importance of using the WHO classification system and demographic factors to gauge their prognosis., (© 2018 S. Karger AG, Basel.)

A catalytic [2+2+2] cyclotrimerization of unactivated internal alkynes providing cyclotrimerization products in excellent yields with high regioselectivity is described. The transformation is accomplished by using a simple catalytic mixture comprising Ni(acac) 2 , an imidazolium salt and a Grignard reagent at room temperature or 60 °C for 20 min or 1 h., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Deprotonation of functional salicylaldimines with NaH invariably results in cubane or double-cubane Na(I) aggregates which transmetallate with Ni(II) under different stoichiometric conditions to give Ni(II) complexes that are catalytically active towards ethylene oligomerisation.