Novel compound heterozygous mutations in the hemojuvelin gene in a juvenile hemochromatosis patient: A case report.

BACKGROUND: Juvenile hemochromatosis (JH) is an early-onset, rare autosomal recessive disorder of iron overload observed worldwide that leads to damage in multiple organs. Pathogenic mutations in the hemojuvelin (HJV) gene are the major cause of JH. CASE SUMMARY: A 34-year-old male Chinese patient presented with liver fibrosis, diabetes, hypogonadotropic hypogonadism, hypophysis hypothyroidism, and skin hyperpigmentation. Biochemical test revealed a markedly elevated serum ferritin level of 4329 µg/L and a transferrin saturation rate of 95.4%. Targeted exome sequencing and Sanger sequencing revealed that the proband had a novel mutation c.863G>A (p.R288Q) in the HJV gene which was transmitted from his father, and two known mutations, c.18G>C (p.Q6H) and c.962_963delGCinsAA (p.C321*) in cis, which were inherited from his mother. The p.R288W mutation was previously reported to be pathogenic for hemochromatosis, which strongly supported the pathogenicity of p.R288Q reported for the first time in this case. After 72 wk of intensive phlebotomy therapy, the patient achieved a reduction in serum ferritin to 160.5 µg/L. The patient's clinical symptoms demonstrated a notable improvement. CONCLUSION: This study highlights the importance of screening for hemochromatosis in patients with diabetes and hypogonadotropic hypogonadism. It also suggests that long-term active phlebotomy could efficiently improve the prognosis in severe JH.

'Accelerated' Deactivation of Carbon Nitride Photocatalyst for Solar Hydrogen Evolution.

Carbon nitride photocatalysts are among the most studied candidates for efficient solar hydrogen (H2) production due to their abundance of precursors, suitable bandgap, and visible light utilization. However, the polymeric nature of carbon nitride materials raises concerns regarding the self-decomposition during photocatalytic redox processes. Yet, the operational stability of carbon nitride photocatalysts for solar H2 production remains under-explored. Here we evaluate the photostability of carbon nitride photocatalysts with platinum (Pt) as the co-catalyst for solar H2 evolution and significant deactivation of this photocatalyst is observed under'accelerated' testing conditions. It is demonstrated that the detachment of the Pt co-catalyst on the surface of carbon nitride is the major reason for this deactivation, which can be attributed to a synergistic effect of photo-corrosion and mechanical stirring. The photo-corrosion weakens the interfacial bonding between carbon nitride and Pt co-catalyst, while continuous collisions from the mechanical stirring promote the detachment of co-catalysts from the surface of carbon nitride. These understandings provide insights into the rational design of photocatalysts and photocatalytic systems for improved operational stability.

Insights into the Roles of Natural Killer Cells in Osteoarthritis.

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease.

Thermally Evaporated Metal Halide Perovskites and Their Analogues: Film Fabrication, Applications and Beyond.

Metal halide perovskites emerge as promising semiconductors for optoelectronic devices due to ease of fabrication, attractive photophysical properties, their low cost, highly tunable material properties, and high performance. High-quality thin films of metal halide perovskites are the basis of most of these applications including solar cells, light-emitting diodes, photodetectors, and electronic memristors. A typical fabrication method for perovskite thin films is the solution method, which has several limitations in device reproducibility, adverse environmental impact, and utilization of raw materials. Thermal evaporation holds great promise in addressing these bottlenecks in fabricating high-quality halide perovskite thin films. It also has high compatibility with mass-production platforms that are well-established in industries. This review first introduces the basics of the thermal evaporation method with a particular focus on the critical parameters influencing the thin film deposition. The research progress of the fabrication of metal halide perovskite thin films is further summarized by different thermal evaporation approaches and their applications in solar cells and other optoelectronic devices. Finally, research challenges and future opportunities for both fundamental research and commercialization are discussed.

Unveiling the Role of Water in Heterogeneous Photocatalysis of Methanol Conversion for Efficient Hydrogen Production.

Water molecules, which act as both solvent and reactant, play critical roles in photocatalytic reactions for methanol conversion. However, the influence of water on the adsorption of methanol and desorption of liquid products, which are two essential steps that control the performance in photocatalysis, has been well under-explored. Herein, we reveal the role of water in heterogeneous photocatalytic processes of methanol conversion on the platinized carbon nitride (Pt/C3N4) model photocatalyst. In situ spectroscopy techniques, isotope effects, and computational calculations demonstrate that water shows adverse effects on the adsorption of methanol molecules and desorption processes of methanol oxidation products on the surface of Pt/C3N4, significantly altering the reaction pathways in photocatalytic methanol conversion process. Guided by these discoveries, a photothermal-assisted photocatalytic system is designed to achieve a high solar-to-hydrogen (STH) conversion efficiency of 2.3 %, which is among the highest values reported. This work highlights the important roles of solvents in controlling the adsorption/desorption behaviours of liquid-phase heterogeneous catalysis.

Multiomics Analyses Reveal the Dual Role of Flavonoids in Pigmentation and Abiotic Stress Tolerance of Soybean Seeds.

The color of the seed coat has great diversity and is regarded as a biomarker of metabolic variations. Here we isolated a soybean variant (BLK) from a population of recombinant inbred lines with a black seed coat, while its sibling plants have yellow seed coats (YL). The BLK and YL plants showed no obvious differences in vegetative growth and seed weight. However, the BLK seeds had higher anthocyanins and flavonoids level and showed tolerance to various abiotic stresses including herbicide, oxidation, salt, and alkalinity during germination. Integrated metabolomic and transcriptomic analyses revealed that the upregulation of biosynthetic genes probably contributed to the overaccumulation of flavonoids in BLK seeds. The transient expression of those biosynthetic genes in soybean root hairs increased the levels of total flavonoids or anthocyanins. Our study revealed the molecular basis of flavonoid accumulation in soybean seeds, leveraging genetic engineering for both nutritious and stress-tolerant soybean germplasm.

Smad4 sequestered in SFPQ condensates prevents TGF-ß tumor-suppressive signaling.

Loss of TGF-ß growth-inhibitory responses is a hallmark of human cancer. However, the molecular mechanisms underlying the TGF-ß resistance of cancer cells remain to be fully elucidated. Splicing factor proline- and glutamine-rich (SFPQ) is a prion-like RNA-binding protein that is frequently upregulated in human cancers. In this study, we identified SFPQ as a potent suppressor of TGF-ß signaling. The ability of SFPQ to suppress TGF-ß responses depends on its prion-like domain (PrLD) that drives liquid-liquid phase separation (LLPS). Mechanistically, SFPQ physically restrained Smad4 in its condensates, which excluded Smad4 from the Smad complex and chromatin occupancy and thus functionally dampened Smad-dependent transcriptional responses. Accordingly, SFPQ deficiency or loss of phase separation activities rendered human cells hypersensitive to TGF-ß responses. Together, our data identify an important function of SFPQ through LLPS that suppresses Smad transcriptional activation and TGF-ß tumor-suppressive activity.

Arbuscular mycorrhizal fungi improve selenium uptake by modulating root transcriptome of rice (Oryza sativa L.).

Although selenium (Se) is an essential trace element in humans, the intake of Se from food is still generally inadequate throughout the world. Inoculation with arbuscular mycorrhizal fungi (AMF) improves the uptake of Se in rice (Oryza sativa L.). However, the mechanism by which AMF improves the uptake of Se in rice at the transcriptome level is unknown. Only a few studies have evaluated the effects of uptake of other elements in rice under the combined effects of Se and AMF. In this study, Se combined with the AMF Funneliformis mosseae (Fm) increased the biomass and Se concentration of rice plants, altered the pattern of ionomics of the rice roots and shoots, and reduced the antagonistic uptake of Se with nickel, molybdenum, phosphorus, and copper compared with the treatment of Se alone, indicating that Fm can enhance the effect of fertilizers rich in Se. Furthermore, a weighted gene co-expression network analysis (WGCNA) showed that the hub genes in modules significantly associated with the genes that contained Se and were related to protein phosphorylation, protein serine/threonine kinase activity, membrane translocation, and metal ion binding, suggesting that the uptake of Se by the rice roots may be associated with these genes when Fm and Se act in concert. This study provides a reference for the further exploration of genes related to Se uptake in rice under Fm treatment.

Chiral bifunctional organocatalysts for enantioselective synthesis of 3-substituted isoindolinones.

A series of chiral bifunctional organocatalysts were prepared and used for enantioselective synthesis of 3-substituted isoindolinones from 2-formylarylnitriles and malonates through aldol-cyclization rearrangement tandem reaction in excellent yields and enantioselectivites (up to 87% yield and 95% ee) without recrystallization. In this investigation, we found that chiral tertiary-amine catalysts with a urea group can afford 3-substituted isoindolinones both in higher yields (87% vs. 77%) and enantioselectivities (95% ee vs. 46% ee) than chiral bifunctional phase-transfer catalysts.

High-sensitivity profiling of SARS-CoV-2 noncoding region-host protein interactome reveals the potential regulatory role of negative-sense viral RNA.

A deep understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-host interactions is crucial to developing effective therapeutics and addressing the threat of emerging coronaviruses. The role of noncoding regions of viral RNA (ncrRNAs) has yet to be systematically scrutinized. We developed a method using MS2 affinity purification coupled with liquid chromatography-mass spectrometry and designed a diverse set of bait ncrRNAs to systematically map the interactome of SARS-CoV-2 ncrRNA in Calu-3, Huh7, and HEK293T cells. Integration of the results defined the core ncrRNA-host protein interactomes among cell lines. The 5' UTR interactome is enriched with proteins in the small nuclear ribonucleoproteins family and is a target for the regulation of viral replication and transcription. The 3' UTR interactome is enriched with proteins involved in the stress granules and heterogeneous nuclear ribonucleoproteins family. Intriguingly, compared with the positive-sense ncrRNAs, the negative-sense ncrRNAs, especially the negative-sense of 3' UTR, interacted with a large array of host proteins across all cell lines. These proteins are involved in the regulation of the viral production process, host cell apoptosis, and immune response. Taken together, our study depicts the comprehensive landscape of the SARS-CoV-2 ncrRNA-host protein interactome and unveils the potential regulatory role of the negative-sense ncrRNAs, providing a new perspective on virus-host interactions and the design of future therapeutics. Given the highly conserved nature of UTRs in positive-strand viruses, the regulatory role of negative-sense ncrRNAs should not be exclusive to SARS-CoV-2. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic affecting millions of lives. During replication and transcription, noncoding regions of the viral RNA (ncrRNAs) may play an important role in the virus-host interactions. Understanding which and how these ncrRNAs interact with host proteins is crucial for understanding the mechanism of SARS-CoV-2 pathogenesis. We developed the MS2 affinity purification coupled with liquid chromatography-mass spectrometry method and designed a diverse set of ncrRNAs to identify the SARS-CoV-2 ncrRNA interactome comprehensively in different cell lines and found that the 5' UTR binds to proteins involved in U1 small nuclear ribonucleoprotein, while the 3' UTR interacts with proteins involved in stress granules and the heterogeneous nuclear ribonucleoprotein family. Interestingly, negative-sense ncrRNAs showed interactions with a large number of diverse host proteins, indicating a crucial role in infection. The results demonstrate that ncrRNAs could serve diverse regulatory functions.

Full-length transcriptome sequencing and transgenic tobacco revealed the key genes in the chlorogenic acid synthesis pathway of Sambucus chinensis L.

Chlorogenic acid is a key chemical in antioxidation and antisepsis. Sambucus chinensis L. is an herbaceous plant rich in chlorogenic acid and a potential genetic resource for breeding high-chlorogenic acid plants. However, there are few studies on the synthesis pathway of chlorogenic acid in S. chinensis. Our study found chlorogenic acid accumulation in S. chinensis to be organ-specific, higher in leaves and buds but lower in roots, stems and fruits. A total number of 546,844 CCS (circular consensus sequence), including 402,767 full-length nonchimeric (FLNC) and 39 annotated sequences related to the synthesis of chlorogenic acid, was obtained by single-molecule real-time sequencing technology (SMRT). qRT-PCR showed that a number of key genes involved in chlorogenic acid synthesis were differentially expressed in various tissues of S. chinensis. Transgenic tobacco revealed that ectopic expression of the HCT homologous gene HCT-45178 increased the content of chlorogenic acid. Our results should be the first report of full-length transcriptome data of S. chinensis, which help to understand the basis of chlorogenic acid synthesis and provide a novel strategy for breeding tobacco cultivars with higher levels of chlorogenic acid.

Addressing the stability challenge of photo(electro)catalysts towards solar water splitting.

The efficiency and stability of photo(electro)catalytic devices are the main criteria towards practical solar fuel production. The efficiency of photocatalysts/photoelectrodes has been intensively pursued and significant progress has been achieved over the past decades. However, the development of durable photocatalysts/photoelectrodes remains one of the biggest challenges for solar fuel production. Moreover, the lack of a feasible and reliable appraisal procedure makes it difficult to evaluate the durability of photocatalysts/photoelectrodes. Herein, a systematic process is proposed for the stability evaluation of photocatalysts/photoelectrodes. A standard operational condition should be used for the stability assessment and the stability results should be reported with the run time, operational stability, and material stability. A widely adopted standardisation for stability assessment will benefit the reliable comparison of results from different laboratories. Furthermore, the deactivation of photo(electro)catalysts is defined as a 50% decrease in productivity. The purpose of the stability assessment should aim to figure out the deactivation mechanisms of photo(electro)catalysts. A deep understanding of the deactivation mechanisms is essential for the design and development of efficient and stable photocatalysts/photoelectrodes. This work will provide insights into the stability assessment of photo(electro)catalysts and advance practical solar fuel production.

Investigation on "Fengshi (GB 31) for treating wind disorders" / 中国针灸

From the perspective of academic history, the paper reviews systematically the background and evolution of the understanding of "Fengshi (GB 31) for treating wind disorders". In the ancient literature, there are no direct relevant statement for the indication of Fengshi (GB 31) associated with "wind", and the consensus on "Fengshi for treating wind disorders" has not been made yet. Under the influence of acupoint theory in recent era and the syndrome differentiation for acupuncture treatment in modern time, this statement becomes a conventional understanding and acceptable gradually. Meanwhile, the understanding for Fengshi (GB 31) treating wind disorders tends to be generalized. Practically, Fengshi (GB 31) is applicable for the various disorders in the local and adjacent areas. It is necessary for modern acupuncture researchers to systematically collate, investigate and identify the knowledge content with a sense of familiarity so that the contemporary inheritance, development and application of traditional theoretical knowledge of acupuncture can be enhanced.

Diagnosis and genetic analysis of a case with Bardet-Biedl syndrome caused by compound heterozygous mutations in the BBS12 gene.

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy, which is caused by mutations mainly in genes encoding BBSome complex and IFT complex. Here, we reported a 21-year-old female with BBS characterized by three primary features including obesity, retinitis pigmentosa sine pigmento and bilateral renal cysts. She also had some secondary features such as diabetes mellitus, nonalcoholic fatty liver disease, subclinical hypothyroidism and mild conductive hearing damage. Whole exome sequencing revealed two compound heterozygous mutations in exon 2 of the BBS12 gene (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) in this patient. Sanger sequencing showed that her father and mother carried c.188delC (p.T63fs) and c.1993_1995del (p.665_665del) variants, respectively, while her parents were free of BBS-related symptoms. In conclusion, this case reported two novel mutations (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) of the BBS12 gene in a girl presented with BBS, which provides novel genetic resources for studies of the disease. Meanwhile, the BBS case shows the entire development progress from her birth to adulthood, which helps facilitate clinicians' understanding of BBS.

Methylation hallmarks on the histone tail as a linker of osmotic stress and gene transcription.

Plants dynamically manipulate their gene expression in acclimation to the challenging environment. Hereinto, the histone methylation tunes the gene transcription via modulation of the chromatin accessibility to transcription machinery. Osmotic stress, which is caused by water deprivation or high concentration of ions, can trigger remarkable changes in histone methylation landscape and genome-wide reprogramming of transcription. However, the dynamic regulation of genes, especially how stress-inducible genes are timely epi-regulated by histone methylation remains largely unclear. In this review, recent findings on the interaction between histone (de)methylation and osmotic stress were summarized, with emphasis on the effects on histone methylation profiles imposed by stress and how histone methylation works to optimize the performance of plants under stress.

Coordination Chemistry Engineered Polymeric Carbon Nitride Photoanode with Ultralow Onset Potential for Water Splitting.

Construction of an intimate film/substrate interface is of great importance for a photoelectrode to achieve efficient photoelectrochemical performance. Inspired by coordination chemistry, a polymeric carbon nitride (PCN) film is intimately grown on a Ti-coated substrate by an in situ thermal condensation process. The as-prepared PCN photoanode exhibits a record low onset potential (Eonset ) of -0.38 V versus the reversible hydrogen electrode (RHE) and a decent photocurrent density of 242 µA cm-2 at 1.23 VRHE for water splitting. Detailed characterization confirms that the origin of the ultralow onset potential is mainly attributed to the substantially reduced interfacial resistance between the Ti-coated substrate and the PCN film benefitting from the constructed interfacial sp2 N→Ti coordination bonds. For the first time, the ultralow onset potential enables the PCN photoanode to drive water splitting without external bias with a stable photocurrent density of ≈9 µA cm-2 up to 1 hour.

H3K27M Mutation Doesn't Mean Worse Prognosis in Old Patients.

Objective: Diffuse midline glioma (DMG), H3K27 altered is a new entity that has become widely recognized. However, studies concerning DMG in adult patients remain rare. We did a retrospective study covering the largest amount of patients to date to analyze the clinicopathological characteristics of diffuse glioma in midline structures of the adult. Methods: We reviewed 108 cases of adult DMG, collected their clinical data, and pathological results including H3K27 mutation. Summarized their features and the connection with overall survival in different age groups. Results: Among 108 cases, 79 tumors were located at the thalamus. 38 patients had H3K27M mutation, whose average age was 35.7 years. The median overall survival of H3K27M-mutant gliomas and the 80 H3K27M wild-type gliomas were both 12 months. For young patients (age ≤ 35), The median survival time of the H3K27M-mutant was 18 months, while that of the H3K27M wild-type was 37 months. For older patients (age>35), the median survival time of the H3K27M-mutant was 16 months, while that of the H3K27M wild-type was 13 months. Other clinicopathological factors including sex, tumor location, the approach of surgery, histological grade, ATRX, and P53 were statistically irrelevant to prognosis. Conclusion: The DMG in adults mainly occurred in the thalamus. H3K27M mutations tend to happen more frequently in young adults, and this genetic alteration results in a worse outcome only in young patients (≤35). For old patients, age is the only independent prognostic factor. Patients who underwent different surgical operations including biopsy, subtotal resection, and total resection had similar prognoses.

Identification and charactering of APX genes provide new insights in abiotic stresses response in Brassica napus.

Ascorbate peroxidase (APX) plays an important role in scavenging H2O2 and balancing ROS content in plant cells, which is of great significance for the growth and development of life and resistance to external stress. However, up to now, APXs in Brassica napus (B. napus) have not been systematically characterized. In this study, a total of 26 BnaAPX genes were identified, which were distributed on 13 chromosomes and divided into five phylogenetic branches. Gene structure analysis showed that they had a wide varied number of exons while BnaAPXs proteins contained more similar motifs in the same phylogenetic branches. qRT-PCR analysis of 26 BnaAPX gene expression patterns showed that three putative cytosol BnaAPX genes BnaAPX1, BnaAPX2, BnaAPX9, two putatice microsomal genes BnaAPX18 and BnaAPX25 were up-regulated rapidly and robustly under high salt, water shortage and high temperature stresses. In addition, the above three abiotic stresses led to a significant increase in APX activity. The results provide basic and comprehensive information for further functional characterization of APX gene family in B. napus.

Patterning of Wafer-Scale MXene Films for High-Performance Image Sensor Arrays.

As a rapidly growing family of 2D transition metal carbides and nitrides, MXenes are recognized as promising materials for the development of future electronics and optoelectronics. So far, the reported patterning methods for MXene films lack efficiency, resolution, and compatibility, resulting in limited device integration and performance. Here, a high-performance MXene image sensor array fabricated by a wafer-scale combination patterning method of an MXene film is reported. This method combines MXene centrifugation, spin-coating, photolithography, and dry-etching and is highly compatible with mainstream semiconductor processing, with a resolution up to 2 µm, which is at least 100 times higher than other large-area patterning methods reported previously. As a result, a high-density integrated array of 1024-pixel Ti3 C2 Tx /Si photodetectors with a detectivity of 7.73 × 1014 Jones and a light-dark current ratio (Ilight /Idark ) of 6.22 × 106 , which is the ultrahigh value among all reported MXene-based photodetectors, is fabricated. This patterning technique paves a way for large-scale high-performance MXetronics compatible with mainstream semiconductor processes.