Complex I deficiency in m.3243A>G fibroblasts is alleviated by reducing NADH accumulation

Introduction: Mitochondrial disease is a spectrum of debilitating disorders caused by mutations in the mitochondrial DNA (mtDNA) or nuclear DNA that compromises the respiratory chain. Mitochondrial 3243A>G (m.3243 A>G) is the most common mutation showing great heterogeneity in phenotype. Previous studies have indicated that NADH: ubiquinone oxidoreductase (complex I) deficiency accompanied by a decreased nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) ratio may play a pivotal role in the pathogenesis of m.3243A>G mutation.Methods: To evaluate the potential effects of strategies targeting the imbalanced NAD+/NADH ratio in m.3243A>G mutation, we treated fibroblasts derived from patients with the m.3243 A>G mutation using nicotinamide riboside (NR) or mitochondria-targeted H2O-forming NADH oxidase (mitoLbNOX).Results: M.3243 A>G fibroblasts showed a significant reduction in complex I core subunit 6, complex I enzymatic activity, complex I-dependent oxygen consumption rate (OCR), and adenosine triphosphate (ATP) production compared to the controls. The NAD+/NADH ratio was also significantly reduced in m.3243 A>G fibroblasts, and, using fluorescence lifetime imaging microscopy, we also found that the NADH level was elevated in m.3243 A>G fibroblasts. After NR treatment, the NAD+/NADH ratio, complex I-dependent OCR, and ATP levels increased, whereas NADH levels remained unchanged. More excitingly, after treatment with mitoLbNOX, the NAD+/NADH ratio, complex I-independent OCR, and ATP levels increased more pronouncedly compared with the NR treatment group, accompanied by significantly reduced NADH levels.Discussion: The present study suggests that compared with repletion of NAD+ alone, the combination of this therapeutic modality with alleviation of NADH overload may amplify the treatment effect of restoring NAD+/NADH balance in m.3243A>G fibroblasts

Hard superconducting gap in PbTe nanowires

Semiconductor nanowires coupled to a superconductor provide a powerful testbed for quantum device physics such as Majorana zero modes and gate-tunable hybrid qubits. The performance of these quantum devices heavily relies on the quality of the induced superconducting gap. A hard gap, evident as vanishing subgap conductance in tunneling spectroscopy, is both necessary and desired. Previously, a hard gap has been achieved and extensively studied in III-V semiconductor nanowires (InAs and InSb). In this study, we present the observation of a hard superconducting gap in PbTe nanowires coupled to a superconductor Pb. The gap size ($\Delta$) is $\sim$ 1 meV (maximally 1.3 meV in one device). Additionally, subgap Andreev bound states can also be created and controlled through gate tuning. Tuning a device into the open regime can reveal Andreev enhancement of the subgap conductance, suggesting a remarkable transparent superconductor-semiconductor interface, with a transparency of $\sim$ 0.96. These results pave the way for diverse superconducting quantum devices based on PbTe nanowires

Recent Advances and New Perspectives in Surgery of Renal Cell Carcinoma

Renal cell carcinoma (RCC) is one of the most common types of cancer in the urogenital system. For localized renal cell carcinoma, nephron-sparing surgery (NSS) is becoming the optimal choice because of its advantage in preserving renal function. Traditionally, partial nephrectomy is performed with renal pedicle clamping to decrease blood loss. Furthermore, both renal pedicle clamping and the subsequent warm renal ischemia time affect renal function and increase the risk of postoperative renal failure. More recently, there has also been increasing interest in creating surgical methods to meet the requirements of nephron preservation and shorten the renal warm ischemia time including assisted or unassisted zero-ischemia surgery. As artificial intelligence increasingly integrates with surgery, the three-dimensional visualization technology of renal vasculature is applied in the NSS to guide surgeons. In addition, the renal carcinoma complexity scoring system is also constantly updated to guide clinicians in the selection of appropriate treatments for patients individually. In this article, we provide an overview of recent advances and new perspectives in NSS

Ballistic PbTe Nanowire Devices

Disorder is the primary obstacle in current Majorana nanowire experiments. Reducing disorder or achieving ballistic transport is thus of paramount importance. In clean and ballistic nanowire devices, quantized conductance is expected with plateau quality serving as a benchmark for disorder assessment. Here, we introduce ballistic PbTe nanowire devices grown using the selective-area-growth (SAG) technique. Quantized conductance plateaus in units of $2e^2/h$ are observed at zero magnetic field. This observation represents an advancement in diminishing disorder within SAG nanowires, as none of the previously studied SAG nanowires (InSb or InAs) exhibit zero-field ballistic transport. Notably, the plateau values indicate that the ubiquitous valley degeneracy in PbTe is lifted in nanowire devices. This degeneracy lifting addresses an additional concern in the pursuit of Majorana realization. Moreover, these ballistic PbTe nanowires may enable the search for clean signatures of the spin-orbit helical gap in future devices

Genome of the rams horn snail Biomphalaria straminea : an obligate intermediate host of schistosomiasis

This work was supported by the Hong Kong Research Grant Council Collaborative Research Fund (C4015-20EF), General Research Fund (14100919), NSFC/RGC Joint Research Scheme (N_CUHK401/21), and The Chinese University of Hong Kong Direct Grant (4053433, 4053489). Y.Y., W.L.S., C.F.W., S.T.S.L., and Y.L. were supported by the Ph.D. studentships of The Chinese University of Hong Kong. A.H. is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/N020146/1). T.B. is supported by a studentship from the Biotechnology and Biological Sciences Research Council-funded South West Biosciences Doctoral Training Partnership (BB/M009122/1). M.E.A.R. is supported by a Ph.D. studentship from the School of Biology and St Andrews University.Background: Schistosomiasis, or bilharzia, is a parasitic disease caused by trematode flatworms of the genus Schistosoma. Infection by Schistosoma mansoni in humans results when cercariae emerge into water from freshwater snails in the genus Biomphalaria and seek out and penetrate human skin. The snail Biomphalaria straminea is native to South America and is now also present in Central America and China, and represents a potential vector host for spreading schistosomiasis. To date, genomic information for the genus is restricted to the neotropical species Biomphalaria glabrata. This limits understanding of the biology and management of other schistosomiasis vectors, such as B. straminea. Findings: Using a combination of Illumina short‐read, 10X Genomics linked‐read, and Hi‐C sequencing data, our 1.005 Gb B. straminea genome assembly is of high contiguity, with a scaffold N50 of 25.3 Mb. Transcriptomes from adults were also obtained. Developmental homeobox genes, hormonal genes, and stress-response genes were identified, and repeat content was annotated (40.68% of genomic content). Comparisons with other mollusc genomes (including Gastropoda, Bivalvia, and Cephalopoda) revealed syntenic conservation, patterns of homeobox gene linkage indicative of evolutionary changes to gene clusters, expansion of heat shock protein genes, and the presence of sesquiterpenoid and cholesterol metabolic pathway genes in Gastropoda. In addition, hormone treatment together with RT-qPCR assay reveal a sesquiterpenoid hormone responsive system in B. straminea, illustrating that this renowned insect hormonal system is also present in the lophotrochozoan lineage. Conclusion: This study provides the first genome assembly for the snail B. straminea and offers an unprecedented opportunity to address a variety of phenomena related to snail vectors of schistosomiasis, as well as evolutionary and genomics questions related to molluscs more widely.Publisher PDFPeer reviewe