Advances in second hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is a widely used treatment for malignant hematological diseases; however, some patients inevitably experience relapse. Therefore, for patients who relapse after the first HSCT (HSCT1), a standard treatment regimen must be developed. A second hematopoietic stem cell transplantation (HSCT2) is a possible treatment option. Several studies have analyzed the feasibility of HSCT2. Previous studies have shown that various factors may affect the efficacy of HSCT2, including the hematopoietic cell transplantation comorbidity index, duration of remission after HSCT1, occurrence of chronic graft-versus-host disease, and disease status before HSCT2. However, the selection of donors for HSCT2 does not affect the transplantation efficacy. HSCT2 also presents a risk of relapse, and the prognosis of patients after relapse is poor. Further research on the treatment of patients after relapse is warranted.

Long-Lasting Heat Dissipation of Flexible Heat Sinks for Wearable Thermoelectric Devices.

Flexible wearable thermoelectric (TE) devices hold great promise for a wide range of applications in human thermal management and self-powered systems. Currently, the main challenge faced by flexible TE devices is the inadequate dissipation of heat, which hinders the maintenance of significant temperature differences over prolonged periods. Most existing heat sinks, being rigid in nature, compromise the overall flexibility of the device. Therefore, the challenge lies in maintaining device flexibility while ensuring effective heat dissipation. In this study, we developed a flexible phase-change material (FPCM) heat sink to address this issue and enhance the heat dissipation capabilities of TE devices (FPCM-TED). When used as a thermoelectric cooler (TEC), the FPCM heat sink efficiently absorbs heat from the hot end, enabling long-lasting and high-performance cooling of the TEC. This capability effectively reduces body temperature by up to 11.21 °C and can be sustained for at least 300 s. Additionally, when employed as a thermoelectric generator (TEG), the FPCM absorbs heat at the cold end, thereby increasing the temperature difference between the hot and cold ends and enhancing the output performance of the device. By integrating FPCM-TED into a fabric wristband, we successfully developed a self-powered wireless pedometer sensing system. This breakthrough lays a solid foundation for the application of wearable, smart clothing.

Instant duodenal decompression after endoscopic retrograde cholangiopancreatography can effectively reduce the incidence of post-ERCP pancreatitis and hyperamylasemia.

Background: Post-ERCP pancreatitis (PEP) is significantly influenced by the reflux of duodenal fluid. While gastrointestinal decompression represents a fundamental approach in acute pancreatitis management, the effectiveness of immediate duodenal decompression following ERCP to prevent PEP remains uncertain. This study aimed to investigate the impact of immediate duodenal decompression after ERCP on reducing the incidence of hyperamylasemia and PEP. Methods: This retrospective study encompassed patients with native papilla who underwent therapeutic ERCP for choledocholithiasis at the Department of Gastroenterology, Chun'an Branch of Zhejiang Provincial People's Hospital (Zhejiang, China) between January 2020 and June 2023. Based on the immediate placement of a duodenal decompression tube post-ERCP, patients were categorized into two groups: the duodenal decompression group and the conventional procedure group. Primary outcomes included the incidence of PEP and hyperamylasemia. Results: A total of 195 patients were enrolled (94 in the duodenal decompression group and 101 in the conventional procedure group). Baseline clinical and procedural characteristics exhibited no significant differences between the two groups. PEP occurred in 2 patients (2.1%) in the duodenal decompression group, in contrast to 11 patients (10.9%) in the conventional procedure group (Risk difference [RD] 8.8%; 95% confidence interval [CI] 1.7%-16.5%, P = 0.014). Hyperamylasemia was observed in 8 patients (8.5%) in the duodenal decompression group, compared to 20 patients (19.8%) in the conventional procedure group (RD 11.3%; 95% CI 1.4%-21.0%; P = 0.025). Patients with PEP in both groups showed improvement after receiving active treatment. No severe cases of PEP occurred in either group, and no serious adverse events related to duodenal catheter decompression were reported. Conclusion: Immediate duodenal decompression following ERCP demonstrates an effective reduction in the incidence of hyperamylasemia and PEP.

The role of Testis-Specific Protein Y-encoded-Like 2 in kidney injury.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Recent findings suggest that Testis-Specific Protein Y-encoded-Like 2 (TSPYL2) plays a fibrogenic role in diabetes-associated renal injury. However, the role of TSPYL2 in IRI-induced kidney damage is not entirely clear. In this study, we found that the expression of TSPYL2 was upregulated in a mouse model of AKI and in the hypoxia/reoxygenation (H/R) cell model. Knockdown of TSPYL2 attenuated kidney injury after IRI. More specifically, the knockdown of TSPYL2 or aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) alleviated renal IRI-induced mitochondrial dysfunction and oxidative stress in vitro and in vivo. Further investigation showed that TSPYL2 regulated SREBP-2 acetylation by inhibiting SIRT1 and promoting p300 activity, thereby promoting the transcriptional activity of ACMSD. In conclusion, TSPYL2 was identified as a pivotal regulator of IRI-induced kidney damage by activating ACMSD, which may lead to NAD+ content and the damaging response in the kidney.

L-arginine alleviates heat stress-induced mammary gland injury through modulating CASTOR1-mTORC1 axis mediated mitochondrial homeostasis.

As global warming intensifies, extreme heat is becoming increasingly frequent. These extreme heatwaves have decreased the milk production of dairy animals such as cows and goats and have caused significant damage to the entire dairy industry. It is known that heat stress (HS) can induce the apoptosis and autophagy of mammary epithelial cells (MECs), leading to a decrease in lactating MECs. L-arginine can effectively attenuate HS-induced decreases in milk yield, but the exact mechanisms are not fully understood. In this study, we found that HS upregulated the arginine sensor CASTOR1 in mouse MECs. Arginine activated mTORC1 activity through CASTOR1 and promoted mitochondrial biogenesis through the mTORC1/PGC-1α/NRF1 pathway. Moreover, arginine inhibited mitophagy through the CASTOR1/PINK1/Parkin pathway. Mitochondrial homeostasis ensures ATP synthesis and a stable cellular redox state for MECs under HS, further alleviating HS-induced damage and improving the lactation performance of MECs. In conclusion, these findings reveal the molecular mechanisms by which L-arginine relieves HS-induced mammary gland injury, and suggest that the intake of arginine-based feeds or feed additives is a promising method to increase the milk yield of dairy animals in extreme heat conditions.

Transcriptomic Analysis Revealed an Important Role of Peroxisome-Proliferator-Activated Receptor Alpha Signaling in Src Homology Region 2 Domain-Containing Phosphatase-1 Insufficiency Leading to the Development of Renal Ischemia-Reperfusion Injury.

In kidney transplantation, the donor kidney inevitably undergoes ischemia-reperfusion injury (IRI). It is of great importance to study the pathogenesis of IRI and find effective measures to attenuate acute injury of renal tubules after ischemia-reperfusion. Our previous study found that Src homology region 2 domain-containing phosphatase-1 (SHP-1) insufficiency aggravates renal IRI. In this study, we systematically analyzed differences in the expression profiles of SHP-1 (encoded by Ptpn6)-insufficient mice and wild-type mice by RNA-seq. We found that a total of 161 genes showed at least a twofold change, with a false discovery rate <0.05 in Ptpn6 +/mev mice after IRI and 42 genes showing more than a fourfold change. Of the eight genes encoding proteins with immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that bind to Ptpn6, three were upregulated, and five were downregulated. We found that for the differentially expressed genes (DEGs) with a fold change >2, the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were the cell division pathway and peroxisome-proliferator activated receptor PPARα signaling pathways. Furthermore, the downregulated genes of the PPARα signaling pathway were mainly related to fatty acid absorption and degradation. Using an agonist of the PPARα signaling pathway, fenofibrate, we found that renal IRI was significantly attenuated in Ptpn6 +/mev mice. In summary, our results show that insufficiency of SHP-1 inhibits the expression of genes in the PPARα signaling pathway, thereby leading to increased reactive oxygen species (ROS) and exacerbating the renal IRI. The PPARα signaling agonist fenofibrate partially attenuates renal IRI induced by SHP-1 insufficiency.

EIF4A3-induced circFIP1L1 represses miR-1253 and promotes radiosensitivity of nasopharyngeal carcinoma.

BACKGROUND: Radiation is currently used to be a mainstay of salvage therapy for nasopharyngeal carcinoma (NPC), however, development of radioresistance largely limits the radiation efficacy. Circular RNAs (circRNAs) have been shown to affect NPC progression, but its role in radioresistance remain unclear. METHODS: The circular structure of circFIP1L1(circ_0069740) was verified by RNA-sequencing, RT-PCR based on gDNA or cDNA, RNase R treatment, and actinomycin D treatment. Cellular localization of circFIP1L1 and miR-1253 was detected by nucleoplasmic separation and/or fluorescence in situ hybridization. Expression of non-coding RNAs and mRNAs was detected by qRT-PCR, protein expression was detected by Western blot. Functionally, EdU, CCK-8, and colony formation experiments were employed to assess cell proliferation, flow cytometry was adopted to estimate cell cycle and apoptosis. Xenograft tumor growth was performed to detect the role of circFIP1L1 in vivo. Mechanistically, we examined the interplay between miR-1253 and circFIP1L1 or EIF4A3 through dual-luciferase reporter assay. The potential regulatory impacts of EIF4A3 on circFIP1L1 or PTEN was examined by RNA immunoprecipitation and RNA pull-down assays. RESULTS: CircFIP1L1 overexpression and miR-1253 knockdown repressed NPC cell proliferation, facilitated NPC cell apoptosis, and enhanced NPC radiosensitivity. Mechanistically, circFIP1L1 was revealed to repress miR-1253 by binding to it, and EIF4A3 is a target gene of miR-1253. CircFIP1L1 regulated NPC proliferation, apoptosis, and radiosensitivity through miR-1253/EIF4A3. Moreover, we found that EIF4A3 bound to FIP1L1 mRNA transcript and induced circFIP1L1 formation, and thus stabilizing PTEN mRNA. CONCLUSION: Our findings suggested that EIF4A3-induced circFIP1L1 repressed NPC cell proliferation, facilitated NPC cell apoptosis, and enhanced NPC radiosensitivity by miR-1253.

CircCRIM1 promotes nasopharyngeal carcinoma progression via the miR-34c-5p/FOSL1 axis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare malignancy with multiple risk factors (Epstein-Barr virus, etc.) that seriously threatens the health of people. CircRNAs are known to regulate the tumorigenesis of malignant tumours, including NPC. Moreover, circCRIM1 expression is reported to be upregulated in NPC. Nevertheless, the impact of circCRIM1 on NPC progression is not clear. METHODS: An MTT assay was performed to assess cell viability. In addition, cell invasion and migration were assessed by the transwell assay. Dual luciferase assays were performed to assess the association among circCRIM1, miR-34c-5p and FOSL1. Moreover, RT-qPCR was applied to assess mRNA levels, and protein levels were determined by Western blot. RESULTS: CircCRIM1 and FOSL1 were upregulated in NPC cells, while miR-34c-5p was downregulated. Knockdown of circCRIM1 significantly decreased the invasion, viability and migration of NPC cells. The miR-34c-5p inhibitor notably promoted the malignant behaviour of NPC cells, while miR-34c-5p mimics exerted the opposite effect. Moreover, circCRIM1 could bind with miR-34c-5p, and FOSL1 was identified to be downstream of miR-34c-5p. Furthermore, circCRIM1 downregulation notably inhibited the proliferation and invasion of NPC cells, while this phenomenon was significantly reversed by FOSL1 overexpression. CONCLUSION: Silencing circCRIM1 inhibited the tumorigenesis of NPC. Thus, circCRIM1 might be a novel target for NPC.

CRISPR/Cas12a Powered DNA Framework-Supported Electrochemical Biosensing Platform for Ultrasensitive Nucleic Acid Analysis.

Nucleic acid analysis using ultrasensitive and simple methods is critically important for the early-stage diagnosis and treatment of diseases. The CRISPR/Cas proteins, guided by a single-stranded RNA have shown incredible capability for sequence-specific targeting and detection. Herein, in order to improve and expand the application of CRISPR/Cas technology to the electrochemical interface-based nucleic acids analysis, the authors develop a CRISPR/Cas12a powered DNA framework-supported electrochemical biosensing platform via the cis and trans cleavage of Cas12a on the heterogeneous carbon interface (the existing publications which commonly adopted trans-cleavage). Their solid-liquid interface is first immobilized by 3D tetrahedral framework nucleic acids (FNAs) with specific DNA recognition probe. Based on the recognition of the complementary target through protospacer adjacent motif (PAM) confirmation and CRISPR-derived RNA (crRNA) matching, the easily formed Cas12a/crRNA duplex can get access to the interface, and the cis and trans cleavage of Cas12a can be easily activated. In combination with the enzyme catalyzed reaction, they achieved an ultralow limit of detection (LOD) of 100 fm in HPV-16 detection without pre-amplification. Furthermore, the platform is compatible with a spike-in human serum sample and has superior stability. Thus, their reported platform offers a practical, versatile, and amplification-free toolbox for ultrasensitive nucleic acid analysis.

One-pot pre-coated interface proximity extension assay for ultrasensitive co-detection of anti-SARS-CoV-2 antibodies and viral RNA.

In the field of in vitro diagnostics, detection of nucleic acids and proteins from biological samples is typically performed with independent platforms; however, co-detection remains a major technical challenge. Specifically, during the coronavirus disease 2019 (COVID-19) pandemic, the ability to simultaneously detect viral RNA and human antibodies would prove highly useful for efficient diagnosis and disease course management. Herein, we present a multiplex one-pot pre-coated interface proximity extension (OPIPE) assay that facilitates the simultaneous recognition of antibodies using a pre-coated antigen interface and a pair of anti-antibodies labeled with oligonucleotides. Following anti-antibody-bound nucleic acid chain extension to form templates in proximity, antibody signals can be amplified, together with that of targeted RNA, via a reverse transcription-polymerase chain reaction. Using four-color fluorescent TaqMan probes, we demonstrate the co-detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies and viral nucleic acids in a single bio-complex sample, including nucleocapsid protein-specific IgG and IgM, and the RNA fragments of RdRp and E genes. The serum detection limit for this platform is 100 fg/mL (0.67 fM) for the anti-SARS-CoV-2 antibody and 10 copies/µL for viral RNA. The OPIPE assay offers a practical and affordable solution for ultrasensitive co-detection of nucleic acids and antibodies from the same trace biological sample without the additional requirement of complicated equipment.

Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown.

Central nervous system diseases commonly occur with the destruction of the blood-brain barrier. As a primary cause of morbidity and mortality, stroke remains unpredictable and lacks cellular biomarkers that accurately quantify its occurrence and development. Here, we identify NeuN+/CD45-/DAPI+ phenotype nonblood cells in the peripheral blood of mice subjected to middle cerebral artery occlusion (MCAO) and stroke patients. Since NeuN is a specific marker of neural cells, we term these newly identified cells as circulating neural cells (CNCs). We find that the enumeration of CNCs in the blood is significantly associated with the severity of brain damage in MCAO mice (p < 0.05). Meanwhile, the number of CNCs is significantly higher in stroke patients than in negative subjects (p < 0.0001). These findings suggest that the amount of CNCs in circulation may serve as a clinical indicator for the real-time prognosis and progression monitor of the occurrence and development of ischemic stroke and other nervous system disease.

Visible-Light Carbon Nitride-Catalyzed Aerobic Cyclization of Thiobenzanilides under Ambient Air Conditions.

A metal-free heterogeneous photocatalysis has been developed for the synthesis of benzothiazoles via intramolecular C-H functionalization/C-S bond formation of thiobenzanilides by inexpensive graphitic carbon nitride (g-C3N4) under visible-light irradiation. This reaction provides access to a broad range of 2-substituted benzothiazoles in high yields under an air atmosphere at room temperature without addition of a strong base or organic oxidizing reagents. In addition, the catalyst was found to be stable and reusable after five reaction cycles.

Pre-coated interface proximity extension reaction assay enables trace protein detection with single-digit accuracy.

Advances in trace protein detection contribute to the early diagnosis of diseases and exploration of stem cell development. The pre-coated interface proximity extension reaction (PIPER) assay enables target protein detection at trace levels and was developed based on protein biomarker recognition using sets of three specific antibodies and the extension of antibody-bound nucleic acid chains in proximity, accompanied by amplification and reading of protein signals via real-time quantitative polymerase chain reaction (qPCR). Noise generated in binding reactions and enzymatic steps was decreased by transferring the liquid-liquid reactions onto a liquid-solid interface in glutaraldehyde-treated tubes pre-coated with antibodies. Nucleic acid sequences of oligo-antibody-based probes were designed for extension and qPCR without pre-amplification when binding to a target molecule. As a proof of concept, the PIPER assay was used to profile slight variations in crucial biomarkers, high-sensitivity C-reactive protein, and cardiac troponin I. The detection sensitivity of the assay for the biomarkers was 0.05 pg/mL (1.25 fM) in 10% human serum. In phosphate-buffered saline, the PIPER assay detected fewer than 10 protein molecules per µL. The simple, widely applicable PIPER assay can detect trace protein biomarkers with single-digit accuracy, making it appropriate for the development of clinical hypersensitive protein detection and single-cell protein detection technology.

Chemoselective Rearrangement Reactions of Sulfur Ylide Derived from Diazoquinones and Allyl/Propargyl Sulfides.

Here, we describe three types of rearrangement reactions of sulfur ylide derived from diazoquinones and allyl/propargyl sulfides. With Rh2(esp)2 as the catalyst, diazoquinones react with allyl/propargyl sulfides to form a sulfur ylide, which undergoes a chemoselective tautomerization/[2,3]-sigmatropic rearrangement reaction, a Doyle-Kirmse rearrangement/Cope rearrangement cascade reaction, or a Doyle-Kirmse rearrangement/elimination reaction, depending on the substituent of the sulfides. The protocol provides alkenyl and allenyl sulfides and multisubstituted phenols with moderate and high yields.

HLA-A*02:01 allele is associated with tanshinone-induced cutaneous drug reactions in Chinese population.

Tanshinone, a widely used Chinese patent medicine, has been confirmed to have various kinds of pharmacological effects although frequently causing cutaneous adverse drug reactions (cADRs). We aim to identify whether human leukocyte antigen (HLA) class I alleles are associated with tanshinone-induced cADRs in Han Chinese. The association study including 18 patients with tanshinone-induced cADRs, 67 tanshinone-tolerant volunteers, and two general population databases consisted of 10,689 and 169,995 healthy subjects was performed. The frequency of tanshinone-induced cADRs patients carrying HLA-A*02:01 was significantly higher when compared with the general control groups (OR = 6.25, Pc = 7.20 × 10-5; OR = 7.14, Pc = 8.00 × 10-6), and with the tolerant group (OR = 5.09, Pc = 0.024). The molecular docking assay confirmed high affinity of the ingredients of tanshinone towards HLA-A*02:01 (≤-7.5 kcal/mol). The result suggested HLA-A*02:01 may work as a promisingly predictive marker for tanshinone personalized therapy in Han Chinese.

SHP-1 inhibits renal ischemia reperfusion injury via dephosphorylating ASK1 and suppressing apoptosis.

Apoptosis of tubular epithelium cells (TECs) plays critical roles in renal ischemia reperfusion (I/R) injury, but the molecular regulatory mechanisms of apoptosis still require further investigation. Recently, phosphatase family members have been suggested to regulate multiple aspects of the injury and regeneration response. However, the roles of SHP-1, an important protein-tyrosine phosphatase, in the regulation of renal I/R injury remain unknown. Here, we found that SHP-1 knockdown in vivo significantly increased renal I/R injury and aggravated the apoptosis of TECs. Consistently, after SHP-1 knockdown in TECs in vitro, a sharp increase of apoptosis induced by cobalt dichloride was found. The protective role of SHP-1 was also validated in a TEC cell line stably overexpressing SHP-1. Mechanistically, the ASK1/MKK4/JNK pro-apoptosis signal was over activated after SHP-1 knockdown, and SHP-1 could bind to and dephosphorylate ASK1 to inhibit its activation, thus repressing apoptosis.

HLA-C*12:02 is strongly associated with Xuesaitong-induced cutaneous adverse drug reactions.

Xuesaitong (XST) is mainly used to treat cardiovascular and cerebrovascular diseases, sometimes causing cutaneous adverse drug reactions (cADRs) with unknown mechanisms of pathogenicity or risk factors. We aimed to verify whether human leukocyte antigen (HLA) alleles are associated with XST-related cADRs in Han Chinese population. We carried out an association study including 12 subjects with XST-induced cADRs, 283 controls, and 28 XST-tolerant subjects. Five out of 12 patients with XST-induced cADRs carried HLA-C*12:02, and all of them received XST via intravenous drip. The carrier frequency of HLA-C*12:02 was significantly high compare to that of the control population (Pc = 4.4 × 10-4, odds ratio (OR) = 21.75, 95% CI = 5.78-81.88). Compared with that of the XST-tolerant group, the patients who received XST through intravenous drip presented a higher OR of cADRs (Pc = 0.011, OR = 27.00, 95% CI = 2.58-282.98). The results suggest that HLA-C*12:02 is a potentially predictive marker of XST-induced cADRs in Han Chinese, especially when XST is administered via intravenous drip.

Osteoporosis in postmenopausal women in this decade: a bibliometric assessment of current research and future hotspots.

Postmenopausal osteoporosis (PMOP) has already become a major public health problem. However, there was no bibliometric analysis estimating the evolutionary process of PMOP research. PURPOSE: This study aimed to assess its scientific activity. METHODS: Publications on PMOP were retrieved from Science Citation Index-Expanded (SCI-E) of the Web of Science (WoS) from 2008 to 2018. VOSviewer software was used for data mining and visualization. The quantity of papers, number of citations, citation frequency per year, and H-index were assessed and compared among different countries, institutes, and researchers. RESULTS: A total of 11,142 papers were included and were cited 184,416 times. The USA contributed the most papers (3162), the most citations (83,270 times), and the highest H-index (115). Canada ranked first for the number of papers per million populations and per trillion GDP. Seven of the top ten funding agencies were industries. The key words were stratified into four clusters: cluster 1 ("basic research"), cluster 2 ("diagnosis"), cluster 3 ("treatment"), and cluster 4 ("others"). Average appearing years (AAY) of key words in cluster 1 were the largest compared to those in clusters 2 and 3. For hotspots, "miRNA" showed a relatively latest AAY of 2017.63, followed by "abaloparatide" and "adipokine". CONCLUSION: We concluded that the USA and Europe were the most productive regions on PMOP, with a high prevalence of articles supported by pharmaceutical companies. Key word focus gradually shifted from "diagnosis" to "treatment" and then to precision medicine orientated "basic research". It is recommended to pay attention to potential research hotspots, such as "miRNA," "abaloparatide," and "adipokine".