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These results demonstrate the benefits of a high-concentration LiFSI-THF electrolyte system, generating new possibilities for high-energy-density rechargeable LMBs.A point mutation in Exon 1, 1-3 (ATG>ACG) causes a non-synonymous change to the start codon, which may affect expression.C*01213 differs from C*01020101 by one nucleotide change at nucleotide 655 in exon 4 from T to G.In chemotherapy for childhood acute lymphoblastic leukaemia (ALL), maintenance therapy consisting of oral daily mercaptopurine and weekly methotrexate is important. NUDT15 variant genotype is reportedly highly associated with severe myelosuppression during maintenance therapy, particularly in Asian and Hispanic populations. It has also been demonstrated that acquired somatic mutations of the NT5C2 and PRPS1 genes, which are involved in thiopurine metabolism, are detectable in a portion of relapsed childhood ALL. To directly confirm the significance of the NUDT15 variant genotype and NT5C2 and PRPS1 mutations in thiopurine sensitivity of leukaemia cells in the intrinsic genes, we investigated 84 B-cell precursor-ALL (BCP-ALL) cell lines. Three and 14 cell lines had homozygous and heterozygous variant diplotypes of the NUDT15 gene, respectively, while 4 and 2 cell lines that were exclusively established from the samples at relapse had the NT5C2 and PRPS1 mutations, respectively. Both NUDT15 variant genotype and NT5C2 and PRPS1 mutations were significantly associated with DNA-incorporated thioguanine levels after exposure to thioguanine at therapeutic concentration. Considering the continuous exposure during the maintenance therapy, we evaluated in vitro mercaptopurine sensitivity after 7-day exposure. Mercaptopurine concentrations lethal to 50% of the leukaemia cells were comparable to therapeutic serum concentration of mercaptopurine. Both NUDT15 variant genotype and NT5C2 and PRPS1 mutations were significantly associated with mercaptopurine sensitivity in 83 BCP-ALL and 23 T-ALL cell lines. The present study provides direct evidence to support the general principle showing that both inherited genotype and somatically acquired mutation are crucially implicated in the drug sensitivity of leukaemia cells.DNA origami has been widely used as a modular platform for condensation of functional molecules to assemble optical, electronic, and biological components. However, the heterogeneous condensation with greater diversities in chemical composition templated with DNA origami is still challenging. Herein, a programmable deposition method is developed to precisely condense silver-silica nanohybrids on DNA origami templates. First, the site-specific metallization of Ag is achieved by thiol group-initiated silver reduction at the designed areas of DNA origami. Next, cysteamine is used to selectively modify the condensed Ag surface with positively charged amino groups for creating an electronically different environment for site-specific placement of silica by a modified Stöber method. Using these strategies, customized patterning of both silver and silica on tubular and rectangular DNA origami nanostructures is successfully achieved with nanoscale spatial resolution. These findings will greatly facilitate the development of DNA nanotechnology-based bottom-up nanofabrication.Nearly all proteins are synthesized in the cytosol. The majority of this proteome must be trafficked elsewhere, such as to membranes, to subcellular compartments, or outside of the cell. Proper trafficking of nascent protein is necessary for protein folding, maturation, quality control and cellular and organismal health. To better understand cellular biology, molecular and chemical technologies to properly characterize protein trafficking (and mistrafficking) have been developed and applied. Herein, we take a biochemical perspective to review technologies that enable spatial and temporal measurement of protein distribution, focusing on both the most widely adopted methodologies and exciting emerging approaches.Previous studies have found that "general catharsis", such as hitting sandbags, does not reduce but increases an individual's anger feeling and aggressive behavior. Although the "goal catharsis" that is directed at attacking targets can temporarily relieve anger, there is a risk of increasing the tendency of aggressive personality if it is used for a long time. These findings raise serious doubts and challenges to the traditional view that "anger must be released" held by the classic catharsis theory that many people still trust. selleck chemical The present study compared the effects of "general catharsis" and "goal catharsis" on anger-related responses among Chinese people, and the Chinese written form of catharsis was used in this study. The results showed that after participants were provoked, the aggressive behavior of participants who wrote down their dissatisfaction (general catharsis condition) was significantly higher than that of participants who wrote to attack someone who irritated them (goal catharsis condition) as well as that of participants who completed a simple recall task (control condition), and there was no significant difference in the aggressive behavior level between the latter two cases. These results suggest that the catharsis effect is no better than a simple recall task similar to attention distraction, that is, aggressive catharsis is not an effective way for anger relief.Invited for this month's cover are the collaborating groups of Dr. Mihail Barboiu from Institut Européen des Membranes and Dr. Sebastien Ulrich from Institut des Biomolécules Max Mousseron Montpellier, France and Prof. Yan Zhang from Jiangnan University, Wuxi, China. The cover feature shows an artistic concept describing an evolutionary approach to the generation of dynamic inhibitors and activators of Carbonic Anhydrase toward constitutional self-selection strategies. More information can be found in the Minireview by Mihail Barboiu, and co-workers.

Isolated hypogonadotropic hypogonadism (IHH) is a clinical syndrome described by failure of gonadal function secondary to defects on the synthesis, secretion, or action of the gonadotropin-releasing hormone (GnRH). The secreted glycoprotein SEMA3A binds its receptors NRP1 or NRP2 and PLXNA to participate in axonal projection, dendritic branching, synaptic formation, and neuronal migration. Deficiency in SEMA3A, NRP1, NRP2, and PLXNA1 have been related to abnormal GnRH neuron development in mice and IHH in humans.

The aim of this study was to examine the genotypic and phenotypic spectra of the NRP1, NRP2, and PLXNA1genes in a large cohort of IHH probands from China. We screened NRP1, NRP2, and PLXNA1 variants in Chinese IHH patients by whole exome sequencing and pedigree analysis.

We identified 10heterozygous missense variants in PLXNA1, five heterozygous missense variants in NRP1, and two heterozygous missense variants in NRP2. NRP1 variants were found only in IHH patients with defective olfaction (i.e., Kallmann syndrome, KS). In addition, 85% (17/20) of patients harbored variants in other IHH-associated genes.

Our study greatly enriched the genotypic and phenotypic spectra of PLXNA1, NRP1, and NRP2 in IHH. It may be conducive to the genetic counseling, diagnosis, and treatment of IHH with mutations in the PLXNA1, NRP1, and NRP2genes. Furthermore, our results indicated that NRP1 were strongly linked to hearing loss.

Our study greatly enriched the genotypic and phenotypic spectra of PLXNA1, NRP1, and NRP2 in IHH. It may be conducive to the genetic counseling, diagnosis, and treatment of IHH with mutations in the PLXNA1, NRP1, and NRP2 genes. Furthermore, our results indicated that NRP1 were strongly linked to hearing loss.We aimed to explore the clinical significance of the secondary pedicle amputation of the repair of distal defects with pedicled axial flap. Five patients who underwent pedicled axial flap transfer to repair a large area of skin and soft tissue defects in our hospital were included in this retrospective study. Detailed information including general data and clinical data, such as preoperative complication, type of primary wound, the distance between the primary wound and the donor site (cm), postoperative complications, and types of axial flap were collected. The patients had good joint movement at 6 months after pedicle amputation. At 48 hours after transplantation, except for the last patient (NO.5), there were no obvious complications such as blood supply disorder, infection, and incision dehiscence of the patients, and the flaps survived well. Just after pedicle amputation, 3 and 6 months after pedicle amputation, the flaps survived well with good local morphology. Forty-eight hours after operation, part of the distal flap in the last patient (NO.5) was necrotic. After 6 months of pedicle amputation, part of the flap was transferred to the distal wound again. At 6 months after pedicle amputation, these patients could accept local scars even though the scar of the last patient was obvious. The secondary pedicle amputation of the repair of distal defects with axial flap could avoid the compression of the vascular pedicle in the subcutaneous tunnel between the donor site and the primary wound, which may ensure the bold supply and increase the survival rate of the flap.Organic multi-valued logic (MVL) circuits can substantially improve the data processing efficiency in highly advanced wearable electronics. Organic ternary logic circuits can be implemented by utilizing the negative transconductance (NTC) of heterojunction transistors (H-TRs). To achieve high-performance organic ternary logic circuits, the range of NTC in H-TRs must be optimized in advance to ensure the well-defined intermediate logic state in ternary logic inverters (T-inverters). Herein, a simple and efficient strategy, which enables the systematic control of the range and position of NTC in H-TRs is presented. Each thickness of p-/n-type semiconductor in H-TRs is adjusted to control the channel conductivity. Furthermore, asymmetric source/drain (S/D) electrode structure is newly developed for H-TRs, which can adjust the amount of hole and electron injection, independently. Based on the semiconductor thickness variation and asymmetric S/D electrodes, the T-inverter exhibits full-swing operation with three distinguishable logic states, resulting in unprecedentedly high static noise margin (≈48% of the ideal value). Moreover, a flexible T-inverter with an ultrathin polymer dielectric is demonstrated, whose operating voltage is less than 8 V. The proposed strategy is fully compatible with the conventional integrated circuit design, which is highly desirable for broad applicability and scalability for various types of T-inverter production.

It is uncertain if the combination of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and renin-angiotensin-aldosterone system inhibitors (RAAS-Is) provides better cardio-renal clinical outcomes in people with type 2 diabetes mellitus (T2DM) compared with SGLT2-Is alone. Using a systematic review and meta-analysis of randomized controlled trials (RCTs), we evaluated the efficacy and safety with respect to cardio-renal outcomes of the combination of SGLT2 and RAAS inhibitorsvs SGLT2-Is in patients with T2DM.

Studies were identified from MEDLINE, Embase, the Cochrane Library and search of bibliographies to May 2021. The Cochrane risk of bias tool was used to assess the risk of bias of each study. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. Quality of the evidence was assessed using GRADE.

Nine articles comprising 8 RCT evaluations (n=34,551 participants) that compared SGLT2-Is with placebo in patients with T2DM against a background of standard care and reported subgroup results for those treated with or without RAAS-Is at baseline were included.