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Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu 2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu 2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships. This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Gout is a hyperuricemia (HUA)-related inflammatory reaction in the joints. Leech therapy has been effective in the gout, but the exact mechanism is unclear., Objectives: In this study, an exploration of the therapeutic mechanism of leech therapy in HUA and gouty arthritis (GA) rats was done., Material and Methods: HUA and GA construction utilizing sodium urate crystal, the potassium form of oxygen oxazine acid, and adenine. Serum and tissues were collected to measure uric acid (UA), creatinine (Cr), and urea nitrogen (UN). Enzyme linked immunosorbent assay was executed to evaluate the levels of xanthine oxidase (XOD), interleukin-6 (IL-6)and tumor necrosis factor α (TNF-α). The expression of glucose transporter 9 (GLUT9), organic anion transporter 3 (OAT3), adenosine triphosphate (ATP)-binding cassette efflux transporter G2 (ABCG2) and the nuclear factor kappa B (NF-kB), interleukin-1β (IL-1β), Toll-like Receptor 2 (TLR2) were assessed by Western blot and visualized in immunohistochemistry staining., Results: Leech therapy reduces the levels of UA, Cr, and UN as well as the liver and serum levels of XOD activity, increasing the expressions of GLUT9, ABCG2, and OAT3 in the kidney. Meanwhile, it reduces joint swelling and lowers the levels of TNF-α, IL-6, IL-1β, TLR2, and NF-kB., Conclusions: Leech therapy regulates the metabolism of uric acid and treats gouty arthritis with an anti-inflammatory effect., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Metformin, a widely used anti-diabetic drug, has demonstrated its efficacy in addressing various inflammatory conditions. tRNA-derived small RNA (tsRNA), a novel type of small non-coding RNA, exhibits diverse regulatory functions and holds promise as both a diagnostic biomarker and a therapeutic target for various diseases. The purpose of this study is to investigate whether the abundance of tsRNAs changed in LPS versus LPS + metformin-treated cells, utilizing microarray technology. Firstly, we established an in vitro lipopolysaccharide (LPS)-induced inflammation model using RAW264.7 macrophages and assessed the protective effects of metformin against inflammatory damage. Subsequently, we extracted total RNA from both LPS-treated and metformin + LPS-treated cell samples for microarray analysis to identify differentially abundant tsRNAs (DA-tsRNAs). Furthermore, we conducted bioinformatics analysis to predict target genes for validated DA-tsRNAs and explore the biological functions and signaling pathways associated with DA-tsRNAs. Notably, metformin was found to inhibit the inflammatory response in RAW264.7 macrophages. The microarray results revealed a total of 247 DA-tsRNAs, with 58 upregulated and 189 downregulated tsRNAs in the Met + LPS group compared to the LPS group. The tsRNA-mRNA network was visualized, shedding light on potential interactions. The results of bioinformatics analysis suggested that these potential targets of specific tsRNAs were mainly related to inflammation and immunity. Our study provides compelling evidence that metformin exerts anti-inflammatory effects and modulates the abundance of tsRNAs in LPS-treated RAW264.7 macrophages. These findings establish a valuable foundation for using tsRNAs as potential biomarkers for metformin in the treatment of inflammatory conditions., 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 © 2024 Elsevier B.V. All rights reserved.)

Two novel Gram-stain-negative, aerobic, non-motile and rod-shaped bacteria, designated as WL0004 T and XHP0148 T , were isolated from seawater samples collected from the coastal areas of Nantong and Lianyungang, PR China, respectively. Both strains were found to grow at 10-42 °C (optimum, 37 °C) and with 2.0-5.0 % (w/v) NaCl (optimum, 3.0 %). Strain WL0004 T grew at pH 6.0-9.0 (optimum, pH 7.0-8.0), while XHP0148 T grew at pH 6.0-10.0 (optimum, pH 7.0-8.0). The major cellular fatty acids (>10 %) of both strains included summed feature 8 (C 18 : 1  ω 6 c and/or C 18 : 1  ω 7 c ). In addition, strain WL0004 T contained 11-methyl C 18 : 1  ω 7 c and strain XHP0148 T contained C 12 : 0 3-OH. The respiratory quinone of both strains was ubiquinone-10. The G+C content of genomic DNA of strains WL0004 T and XHP0148 T were 62.5 and 63.0 mol%, respectively. Strains WL0004 T and XHP0148 T showed the highest 16S rRNA gene sequence similarity to Ruegeria pomeroyi DSS-3 T (99.4 and 99.0 %, respectively), and the 16S rRNA gene-based phylogenetic analysis indicated that the two strains were closely related to members of the genus Ruegeria . The average nucleotide identity and digital DNA-DNA hybridization values among the two strains and type strains of the genus Ruegeria were all below 95 and 70 %, respectively, and the phylogenetic tree reconstructed from the bac120 gene set indicated that the two strains are distinct from each other and the members of the genus Ruegeria . Based on this phenotypic and genotypic characterization, strains WL0004 T (=MCCC 1K07523 T =JCM 35565 T =GDMCC 1.3083 T ) and XHP0148 T (=MCCC 1K07543 T =JCM 35569 T =GDMCC 1.3089 T ) should be recognized as representing two novel species of the genus Ruegeria and the names Ruegeria marisflavi sp. nov. and Ruegeria aquimaris sp. nov. are proposed, respectively.

Intracortical brain-computer interfaces offer superior spatial and temporal resolutions, but face challenges as the increasing number of recording channels introduces high amounts of data to be transferred. This requires power-hungry data serialization and telemetry, leading to potential tissue damage risks. To address this challenge, this paper introduces an event-based neural compressive telemetry (NCT) consisting of 8 channel-rotating Δ-ADCs, an event-driven serializer supporting a proposed ternary address event representation protocol, and an event-based LVDS driver. Leveraging a high sparsity of extracellular spikes and high spatial correlation of the high-density recordings, the proposed NCT achieves a compression ratio of >11.4×, while consumes only 1 μW per channel, which is 127× more efficient than state of the art. The NCT well preserves the spike waveform fidelity, and has a low normalized RMS error <23% even with a spike amplitude down to only 31 μV.

Objectives: To investigate gadolinium deposition in the liver and brain in a rat model with liver fibrosis (LF) after intravenous administration of gadoxetate disodium (GD) and the histological effects of gadolinium deposition in the liver and brain., Methods: Adult male Sprague-Dawley rats were randomly assigned to one of the three groups: 1) LF group received intraperitoneal injection of carbon tetrachloride (CCl 4 ) for 9 weeks alone; 2) LF&GD group received CCl 4 and intravenous administration of GD (for 5 consecutive days); 3) GD group received olive oil and GD. Seven days after the final injection of GD, the deep cerebellar nuclei (DCN) and liver were excised to determine gadolinium concentrations via inductively coupled plasma mass spectrometry, and histologic staining was performed. Bonferroni's post-hoc test and Wilcoxon rank sum test were used to compare the differences between the three groups., Results: The concentrations of retained gadolinium in the liver in the LF&GD group (2.18 ± 0.44 μg/g) were significantly greater compared to the LF group (0.02 ± 0.01 μg/g, P  < 0.001) and GD group (0.37 ± 0.11 μg/g, P  < 0.001). Also, the concentrations of retained gadolinium in DCN were increased in the LF&GD group (0.13 ± 0.06 μg/g) compared to the LF group (0.01 ± 0.00 μg/g, P  < 0.001) and GD group (0.06 ± 0.02 μg/g, P  = 0.019). No histopathological alterations were detected in the liver and DCN between LF&GD group and LF group., Conclusions: LF aggravated gadolinium deposition in the liver and DCN after administration of GD. However, no significant acute histological alterations were observed due to gadolinium deposition., Competing Interests: 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., (© 2024 The Authors.)

Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression of rheumatoid arthritis (RA). Herein, a strategy of simultaneously promoting FLS apoptosis and inhibiting inflammation as mediated by macrophages is proposed to restore synovial homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) is fabricated for transdermal delivery of dual human serum albumin (HSA)-contained biomimetic nanocomplexes to regulate RA FLS and macrophages. Upon skin insertion, dual nanocomplexes are released rapidly from the MN and accumulate in RA joint microenvironment through both passive and active targeting as mediated by HSA. Thioketal-crosslinked fluorinated polyethyleneimine 1.8 K ( TK PF) was constructed to bind the plasmid encoding pro-apoptotic gene PUMA with HSA coating layer ( TK PF/pPUMA@HSA, TPH). TPH nanocomplexes can upregulate PUMA through RA FLS transfection to trigger efficient apoptosis. Also, HSA nanocomplexes encapsulating the classic anti-inflammatory natural product celastrol (Cel@HSA, CH) can inhibit inflammation of macrophages through blocking NF-κB pathway activation. TPH/CH MN can deplete RA FLS and inhibit M1 macrophage activation, suppress synovial hyperplasia as well as reduce bone and cartilage erosion in a collagen-induced arthritis (CIA) mouse model, demonstrating a promising strategy for efficient RA treatment., (© 2024 The Authors.)

Objective: Accidental pharyngeal fishbone ingestion is a common complaint in ear, nose, and throat clinics. Approximately two-thirds of the accidentally ingested fishbones can be removed using tongue depressors and indirect laryngoscopy. However, the remaining third is challenging to identify and remove using these methods. These difficult fishbones require identification and removal via more advanced approaches. Video-guided laryngoscope is used to deal with difficult fishbones in our center. This study aimed to explore the risk factors for difficult fishbones., Methods: A prospective study was performed at a teaching hospital on 2080 patients. Univariate and multivariate analyses were performed to identify the risk factors., Results: The common fishbone locations were the tonsils (39.8%; defined as STEP-I), tongue base (37.1%), vallecula (13.3%; STEP-II), and hypopharynx (9.8%; STEP-III). With increasing STEP level, the ratio of difficult fishbones correspondingly increased (Z = 13.919, P < .001), and the proportions were 21.1%, 41.9%, and 70% in STEP-I, II, and III, respectively. In particular, fishbones in STEP-III (vs STEP-I) had a higher risk of difficult fishbones (odds ratio [OR]: 11.573, 95% CI: 7.987-16.769). Complaints of neck pain (yes vs no), foreign body sensation (yes vs no), and shorter length of fishbones always had a lower risk of difficult fishbones (OR: 0.455, 95% CI: 0.367-0.564; OR: 0.284, 95% CI: 0.191-0.422; OR: 0.727, 95% CI: 0.622-0.85). Missing teeth (yes vs no), swallowing behavior after fishbone ingestion (yes vs no), and male patients (vs female) had a higher risk of difficult fishbones (OR: 1.9, 95% CI: 1.47-2.456; OR: 1.631, 95% CI: 1.293-2.059; OR: 1.278, 95% CI: 1.047-1.56)., Conclusions: Neck pain, foreign body sensation, fishbone length, patient age and sex, tooth status, and swallowing behavior after fishbone ingestion are independent risk factors for difficult fishbones., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Superelastic alloys used for stents, biomedical implants, and solid-state cooling devices rely on their reversible stress-induced martensitic transformations. These applications require the alloy to sustain high deformability over millions of cycles without failure. Here, we report an alloy capable of enduring 10×10^{7} tensile stress-induced phase transformations while still exhibiting over 2% recoverable elastic strains. After millions of cycles, the alloy is highly reversible with zero stress hysteresis. We show that the major martensite variant is reversible even after multimillions of cycles under tensile loadings with a highly coherent (11[over ¯]0)&#95;{A} interface. This discovery provides new insights into martensitic transformation, and may guide the development of superelastic alloys for multimillion cycling applications.

Elastocaloric cooling has emerged as an eco-friendly technology capable of eliminating greenhouse-gas refrigerants. However, its development is limited by the large driving force and low efficiency in uniaxial loading modes. Here, we present a low-force and energy-efficient elastocaloric air cooling approach based on coil-bending of NiTi ribbons/wires. Our air cooler achieves continuous cold outlet air with a temperature drop of 10.6 K and a specific cooling power of 2.5 W g -1 at a low specific driving force of 26 N g -1 . Notably, the cooler shows a system coefficient of performance of 3.7 (ratio of cooling power to rotational mechanical power). These values are realized by the large specific heat transfer area (12.6 cm 2  g -1 ) and the constant cold zone of NiTi wires. Our coil-bending system exhibits a competitive performance among caloric air coolers., (© 2023. The Author(s).)

This study aimed to explore the role and mechanism of DYRK1a regulating ferroptosis of cardiomyocytes during myocardial ischemia-reperfusion injury (MIRI). H9c2 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R) were used as MIRI cell models and transfected with sh-DYRK1a or/and erastin. Cell viability, apoptosis, and DYRK1a mRNA/protein expression were measured accordingly. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were determined. The expression of ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, and TFR1) was detected using western blotting. The MIRI rat model was established to explore the possible role of DYRK1a suppression in cell injury and ferroptosis. OGD/R cells showed elevated mRNA and protein expression for DYRK1a. OGD/R cells transfected with sh-DYRK1a showed elevated cell viability, GSH content, increased GPX4 and SLC7A11 expression, suppressed iron content, MDA, ROS, ACSL4, and TFR1 expression, and reduced apoptosis rate, whereas co-transfection of sh-DYRK1a with erastin reversed the attenuation of sh-DYRK1a on MIRI. The suppressive effect of sh-DYRK1a on MI/R injury was confirmed in an MIRI rat model. DYRK1a mediates ferroptosis of cardiomyocytes to deteriorate MIRI progression., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Normalizing inflamed soils including reactive oxygen species (ROS), nitric oxide (NO), cell-free DNA, and regulating inflammation-related seeds such as macrophages, neutrophils, fibroblasts, represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis (RA) treatment. Herein, ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o -phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol (Not@BR/oPDA-PEG, NBOP NPs). The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation, but also decrease cytokines and chemokines to prevent immune cell recruitment. Specifically, NBOP NPs responded to high level ROS and NO, and disintegrated to release notopterol in inflamed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic ones. The released notopterol could inhibit the JAK-STAT pathway of inflammatory cells to reduce the secretion of pro-inflammatory cytokines and chemokines. This strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation, achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat model. Taken together, our work offered a reference to adjust RA soils and seeds for enhanced RA treatment., Competing Interests: The authors declare no conflicts of interest., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

A Gram-stain-negative, yellow-pigmented, non-motile, rod-shaped, catalase-positive, strictly aerobic marine bacterium, designated XHP0103 T , was isolated from seawater collected from the southern Yellow Sea, PR China (34° 45' 53″ N 119° 25' 30″ E). Strain XHP0103 T grew optimally at 28 °C, pH 7.5 and in 1.0-3.0 % (w/v) sea salt. MK-6 was the major respiratory quinone. The major cellular fatty acids (>10%) were iso-C 15 : 0 , iso-C 15 : 1 G and iso-C 17 : 0 3-OH. The polar lipid profile contained phosphatidylethanolamine, an unidentified aminolipid, an unidentified glycolipid and an unidentified lipid. Results of 16S rRNA gene sequence analysis indicated that strain XHP0103 T displayed highest sequence similarity to Aestuariibaculum marinum IP7 T (94.1 %). However, the phylogenetic trees based on 16S rRNA gene sequences suggested that strain XHP0103 T clustered with Tamlana crocina HST1-43 T (93.4 % sequence similarity) and Aestuariivivens insulae AH-MY3 T (93.5 %). Genome sequencing revealed that strain XHP0103 T comprised 3 134 388 bp with 2770 protein-coding genes, and the DNA G+C content was 35.5 %. The average nucleotide identity and digital DNA-DNA hybridization values between strain XHP0103 T and T. crocina HST1-43 T were 73.6 and 17.3 %, respectively. Based on phylogenetic, phenotypic, genomic and chemotaxonomic evidence, strain XHP0103 T represents a novel genus in the family Flavobacteriaceae , for which the name Marixanthotalea marina gen. nov., sp. nov. is proposed. The type strain is XHP0103 T (=MCCC 1K06060 T =JCM 34682 T ).

The relationship between brain structure alteration and metabolic product clearance after night shift work with total sleep deprivation (SD) remains unclear. Twenty-two intensive care unit staff on regularly rotating shift work were implemented with structural and diffusion MRI under both rest wakefulness (RW) and SD conditions. Peripheral blood samples were collected for the measurement of cerebral metabolites. Voxel-based morphometry and diffusion tensor imaging analysis were used to investigate the alterations in the gray matter density (GMD) and mean diffusivity (MD) within the participants. Furthermore, correlation analysis was performed to investigate the relationship between the neuroimaging metrics and hematological parameters. A significant increase in the GMD values was observed in the anterior and peripheral areas of the brain under SD. In contrast, a decrease in the values was observed in the posterior regions, such as the bilateral cerebellum and thalamus. In addition, a significant reduction in the total cerebrospinal fluid volume was observed under SD. The Aβ42/Aβ40 levels in participants under SD were significantly lower than those under RW. The mean MD increment values extracted from the region of interest (ROI) of the anterior brain were negatively correlated with the increment of plasma Aβ42/Aβ40 levels (r = -0.658, P = 0.008). The mean GMD decrement values extracted from the posterior ROI were positively correlated with the increment of plasma Aβ-40 levels (r = 0.601, P = 0.023). The findings of this study suggest that one night of shift work under SD induces extensive and direction-specific structural alterations of the brain, which are associated with aberrant brain metabolic waste clearance., Competing Interests: Declaration of Competing Interest The authors declare that there are no competing financial interests in relation to the work described., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Carbon dots (CDs) have emerged as potential biomaterials for bioimaging and antimicrobial applications. However, the lack of tunable long-wavelength emission performance and imprecise antibacterial mechanism limit their practical application. Thus, developing versatile CDs that combine outstanding optical performance and excellent antibacterial activity is of great practical significance. Herein, we prepared a novel nitrogen and fluorine co-doped CDs (N, F-CDs) from o-phenylenediamine and 2,3,5,6-tetrafluoroterephthalic acid, which exhibit high fluorescence quantum yield of 52.2%, large Stokes shift of 112 nm, as well tunable multicolor emission light from blue to red region. Thanks to the high biocompatibility and excellent photostability, the N, F-CDs were successfully implemented to multicolor biolabeling of mammalian cells, protozoan cells and plant cells. Moreover, the negatively charged N, F-CDs hold inherent efficient antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). By thoroughly studying the underlying antibacterial mechanisms at the molecular level through real-time quantitative PCR assay, we found the expression of related genes was notably down-regulated, further demonstrated that N, F-CDs against two bacterial strains had distinct target pathways. Our work provides a new reference for developing highly fluorescent multicolor CDs, and may facilitate the design and application of CDs-based nanomaterials in biological environment., 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 Elsevier B.V. All rights reserved.)

A Gram-stain-negative, aerobic, non-motile and rod-shaped strain, designated LJY008 T , was isolated from the intestinal of Eriocheir sinensis in Pukou base of Jiangsu Institute of Freshwater Fisheries. Strain LJY008 T could grow at 4-37 ℃ (optimum, 30 ℃), pH 6.0-8.0 (optimum, pH 7.0), and with 1.0-6.0% NaCl (w/v; optimum, 1.0%). Strain LJY008 T shared highest 16S rRNA gene sequence similarity with Jinshanibacter zhutongyuii CF-458 T (99.3%), followed by J. allomyrinae BWR-B9 T (99.2%), Insectihabitans xujianqingii CF-1111 T (97.3%), and Limnobaculum parvum HYN0051 T (96.7%). The major polar lipids include phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The only respiratory quinone was Q8, and the main fatty acids (> 10%) were C 16:0 , summed feature 3 (C 16:1 ω7c/C 16:1 ω6c), summed feature 8 (C 18:1 ω7c), and C 14:0. The genome-based phylogenies showed that strain LJY008 T was closely associated with members of the genus Jinshanibacter, Insectihabitans, and Limnobaculum. The average nucleotide identities and average amino acid identities (AAI) among strain LJY008 T and closely related neighbours were all below 95%, and the digital DNA-DNA hybridization values among them were all below 36%. The genomic DNA G + C content of strain LJY008 T was 46.1%. Based on the phenotypic, phylogenetic, biochemical and chemotaxonomic analysis, strain LJY008 T represents a novel species of the genus Limnobaculum, for which the name Limnobaculum eriocheiris sp. nov. is proposed. The type strain is LJY008 T (= JCM 34675 T  = GDMCC 1.2436 T  = MCCC 1K06016 T ). In addition, the genera Jinshanibacter and Insectihabitans were reclassified as Limnobaculum, because there was no significant genome-scale divergence or diagnosable difference on phenotypic and chemotaxonomic traits, such as strains of Jinshanibacter and Insectihabitans sharing AAI values of 93.88-94.96%., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Haemoglobin E (HbE) β-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE β-thalassaemia is due to a point mutation in codon 26 of the human HBB gene on one allele (GAG; glutamatic acid → AAG; lysine, E26K), and any mutation causing severe β-thalassaemia on the other. When inherited together in compound heterozygosity these mutations can cause a severe thalassaemic phenotype. However, if only one allele is mutated individuals are carriers for the respective mutation and have an asymptomatic phenotype (β-thalassaemia trait). Here we describe a base editing strategy which corrects the HbE mutation either to wildtype (WT) or a normal variant haemoglobin (E26G) known as Hb Aubenas and thereby recreates the asymptomatic trait phenotype. We have achieved editing efficiencies in excess of 90% in primary human CD34 + cells. We demonstrate editing of long-term repopulating haematopoietic stem cells (LT-HSCs) using serial xenotransplantation in NSG mice. We have profiled the off-target effects using a combination of circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq) and deep targeted capture and have developed machine-learning based methods to predict functional effects of candidate off-target mutations., (© 2023. The Author(s).)

Gastric cancer is a tumor type characterized by lymph node metastasis and the invasion of local tissues. There is thus a critical need to clarify the molecular mechanisms governing gastric cancer onset and progression to guide the treatment of this disease. Long non-coding RNAs and mRNA expression profiles associated with early and local advanced gastric cancer were examined through microarray analyses, with GO and KEGG analyses being employed as a means of exploring the functional roles of those long non-coding RNAs and mRNAs that were differentially expressed in gastric cancer. In total, 1005 and 1831 lncRNAs and mRNAs, respectively, were found to be differentially expressed between early and local advanced gastric cancer. GO and KEGG analyses revealed several pathways and processes that were dysregulated, including the RNA transport, ECM-receptor interaction, and mRNA splicing pathways. In co-expression networks, E2F1, E2F4, and STAT2 were identified as key transcriptional regulators of these processes. Moreover, thrombospondin-2 was confirmed as being expressed at high levels in more advanced gastric cancer by both the GEO and TCGA databases. RNA-sequencing analyses of SGC-790 cells transfected to express thrombospondin-2 further revealed this gene to enhance NF-kB and TNF pathway signaling activity. These results offer insight into gastric cancer-related regulatory networks and suggest thrombospondin-2 to be an important oncogene that drives the progression of this deadly cancer type., 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. The reviewer YJ declared a shared parent affiliation with the author K-KS to the handling editor at the time of review., (Copyright © 2023 Sun, Zu, Wu, Wang, Hua, Zhang, Shen and Wu.)

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, and its treatment remains a big challenge. The pathogenesis of PD may be related to environmental and genetic factors, and exposure to toxins and gene mutations may be the beginning of brain lesions. The identified mechanisms of PD include α-synuclein aggregation, oxidative stress, ferroptosis, mitochondrial dysfunction, neuroinflammation, and gut dysbiosis. The interactions among these molecular mechanisms complicate the pathogenesis of PD and pose great challenges to drug development. At the same time, the diagnosis and detection of PD are also one of obstacles to the treatment of PD due to its long latency and complex mechanism. Most conventional therapeutic interventions for PD possess limited effects and have serious side effects, heightening the need to develop novel treatments for this disease. In this review, we systematically summarized the pathogenesis, especially the molecular mechanisms of PD, the classical research models, clinical diagnostic criteria, and the reported drug therapy strategies, as well as the newly reported drug candidates in clinical trials. We also shed light on the components derived from medicinal plants that are newly identified for their effects in PD treatment, with the expectation to provide the summary and outlook for developing the next generation of drugs and preparations for PD therapy., (© 2023. The Author(s).)

A Gram-stain-negative, non-motile and coccoid bacterial strain, designated XHP0099 T , was isolated from the coastal water of the Yellow Sea, China. Growth occurred at 20-37 ℃ (optimum, 28 ℃), pH 5.0-9.0 (optimum, pH 7.0-8.0), and with 0-7.0% NaCl (optimum, 2.0-3.0%). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain XHP0099 T was related to members of the genus Paracoccus and shared the highest sequence similarity with "P. siganidrum" M26 (98.2%), followed by P. alkanivorans 4-2  T (97.6%) and P. alkenifer DSM 11593  T (97.4%). The average nucleotide identity, amino acid identity, and digital DNA-DNA hybridization values of strain XHP0099 T against related members in the genus Paracoccus were below the cut-off points proposed for the delineation of a novel species. The major cellular fatty acids (> 10%) were summed feature 8 (C 18:1 ω7c/C 18:1 ω6c), and C 18:0 . The major isoprenoid quinone was Q-10 and the polar lipids contained diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), aminolipid (AL) and unidentified polar lipids (L). The G + C content of the genomic DNA of strain XHP0099 T was 66.0%. Genomic analysis suggested that strain XHP0099 T harbored gene clusters for formaldehyde and the XoxF-type methanol oxidation and type 1 Calvin cycle, which could confer the methylotrophy pathway. Based on the phenotypic, phylogenetic, biochemical and chemotaxonomic analysis, strain XHP0099 T represents a novel species of the genus Paracoccus, for which the name Paracoccus marinaquae sp. nov. is proposed. The type strain is XHP0099 T (= JCM 34661  T  = GDMCC 1.2414  T  = MCCC 1K05846 T )., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A Gram-staining-positive, non-motile, aerobic, spherical actinobacterium, designated WL0053 T , was isolated from the coastal sediment of Nantong City, Jiangsu Province, China. The 16S rRNA gene sequence of strain WL0053 T exhibited the highest similarities to Nocardioides mesophilus MSL-22 T (98.0%), N. massiliensis GD12 T (97.8%), Marmoricola bigeumensis MSL-05 T (97.6%), and N. jensenii DSM 20641 T (97.3%). The polyphasic taxonomic approach was used for the identification of strain WL0053 T . This strain formed white, round, and smooth colonies and grew in the presence of 0-18% (w/v) NaCl (optimum, 0-4.0%), at pH 6.0-9.0 (optimum, pH 7.0) and at 20-37 °C (optimum, 28 °C). The main cellular fatty acids comprised of C 17:1 ω8c, C 18:1 ω9c, and iso-C 16:0 . The genomic DNA G + C content was 71.9%. The predominant quinone was MK-8(H 4 ), and the major polar lipid consisted of phosphatidylcholine, glycolipid, phosphatidylethanolamine, and two unidentified phospholipids. Phylogenetic trees of 16S rRNA gene and bac120 gene set indicted that strain WL0053 T was closely related to the species N. iriomotensis and N. mesophilus, while these two species clustered in a separate clade together with M. caldifontis YIM 730233 T in the bac120 tree. Combined with the analysis of average nucleotide identity (ANI), average amino acid identity (AAI), and digital DNA-DNA hybridization (dDDH), it can be considered that the strain WL0053 T is a new member of the genus Nocardioides and is proposed to be named as Nocardioides jiangsuensis sp. nov.. The type strain is WL0053 T (=MCCC 1K05897 T =JCM 34671 T =GDMCC 4.192 T ). Furthermore, based on the fact that the genera Nocardioides and Marmoricola both appeared polyphyletic with no significant difference on phenotypic and chemotaxonomic traits, we proposed to reclassify the genus Marmoricola as Nocardioides., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate two advanced diffusion models, diffusion kurtosis imaging and the newly proposed mean apparent propagation factor-magnetic resonance imaging, in the grading of gliomas and the assessing of their proliferative activity., Methods: Fifty-nine patients with clinically diagnosed and pathologically proven gliomas were enrolled in this retrospective study. All patients underwent DKI and MAP-MRI scans. Manually outline the ROI of the tumour parenchyma. After delineation, the imaging parameters were extracted using only the data from within the ROI including mean diffusion kurtosis (MK), return-to-origin probability (RTOP), Q-space inverse variance (QIV) and non-Gaussian index (NG), and the differences in each parameter in the classification of glioma were compared. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of these parameters., Results: MK, NG, RTOP and QIV were significantly different amongst the different grades of glioma. MK, NG and RTOP had excellent diagnostic value in differentiating high-grade from low-grade glioma, with largest areas under the curve (AUCs; 0.929, 0.933 and 0.819, respectively; P < 0.01). MK and NG had the largest AUCs (0.912 and 0.904) when differentiating grade II tumours from III tumours (P < 0.01) and large AUCs (0.791 and 0.786) when differentiating grade III from grade IV tumours. Correlation analysis of tumour proliferation activity showed that MK, NG and QIV were strongly correlated with the Ki-67 LI (P < 0.001)., Conclusion: MK, RTOP and NG can effectively represent the microstructure of these altered tumours. Multimodal diffusion-weighted imaging is valuable for the preoperative evaluation of glioma grade and tumour proliferative activity., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cement polystyrene shell mold (CPSM) grid concrete walls have been widely applied in the construction of low and mid-rise buildings with higher load-bearing and insulation properties. A star-type grid concrete wall was constructed based on the infill wall simplified to an equivalent diagonal bracing model. To investigate the seismic responses and behavior of a star-type grid concrete wall structure, an overall time-history numerical simulation was carried out in this paper. Typical results, including acceleration, deformation, hysteresis curve and failure pattern of this novel construction system, were interpreted. Results indicate that the star-type grid concrete wall structure has satisfactory seismic performance, including energy dissipation capacity. The structure has higher lateral stiffness and can work in an elastic state under major earthquakes. Accordingly, it is more sensitive to near-fault ground motion with higher frequency components. Meanwhile, the structural inter-story drift angle is less than the limit value of lighter damage when subjected to a super-major earthquake, and the structure presents shear deformation. The openings significantly affect the failure mode, the star-type grid concrete wall with a window (a small aspect ratio less than 1.11) conforms to shear failure, and the wall with a door (aspect ratio of 2.5) conforms to bending-shear failure. The diagonal bracing can distribute the stress in the wall, especially the concrete lattice beam, and effectively resist the lateral forces via the concrete lattice column, improving the ductility and integrity of the structural system.

Background: Although some robotic systems have been developed to improve conventional flexible ureteroscopy (FURS), a widely used intervention in urology, these robots rarely have a comprehensive force feedback function which is important for master-slave controlled surgical robots., Methods: Here, we design and fabricate a novel FURS robot with a comprehensive force feedback function. Moreover, to realize better force feedback, a neural network-based method is also demonstrated to estimate the interactive forces between the flexible ureteroscope and the environment., Results: We show that when teleoperating the flexible ureteroscope with our robot, the operator can accurately feel the obstruction if the interactive axial force or torque exceeds 1.2 N or 15.6 mN·m respectively. For bending movement, augmented force feedback greatly improves the accuracy of the operator's perception of obstruction., Conclusions: The developed robotic system with force feedback is expected to improve the safety of robot-assisted FURS., (© 2022 John Wiley & Sons Ltd.)

A novel bacterium, designated YYF0007 T , was isolated from an agar-degrading co-culture. The strain was found harboring four CRISPR-Cas systems of two classes in the chromosome and subsequently subjected to a study on polyphasic taxonomy. Pairwise analyses of the 16S rRNA gene sequences indicated that strain YYF0007 T had highest 16S rRNA gene sequence similarity (92.2%) to Jiulongibacter sediminis JN-14-9 T . The phylogenomic trees based on the 16S rRNA gene and 269 single-copy orthologous gene clusters (OCs) indicated that strain YYF0007 T should be recognized as a novel genus of the family Spirosomaceae. The cells were Gramstain-negative, nonmotile, strictly aerobic, and straight long rods with no flagellum. Optimum growth occurred at 28°C and pH 7.0 with the presence of NaCl concentration 1.0-3.0% (w/v). The strain showed oxidase and catalase activities. The major fatty acids were C 16:1 ω5c, iso-C 15:0 and summed feature 3 (C 16:1 ω7c and/or C 16:1 ω6c). The predominant isoprenoid quinone was MK-7. The complete genome size was 4.64 Mb with a DNA G + C content of 44.4%. Further typing of CRISPR-Cas systems in the family Spirosomaceae and the phylum Bacteroidota indicated that it was remarkable for strain YYF0007 T featured by such a set of CRISPR-Cas systems. This trait highlights the applications of strain YYF-0007 T in studies on the evolutionary dynamics and bacterial autoimmunity of CRISPR-Cas system as a potential model. The name Marinilongibacter aquaticus gen. nov., sp. nov. is proposed, and the type strain is YYF0007 T (= MCCC 1K06017 T = GDMCC 1.2428 T = JCM 34683 T )., (© 2022. Author(s).)

As an emerging cancer therapeutic target, non-apoptotic cell death such as ferroptosis, necroptosis and pyroptosis, etc., has revealed significant potential in cancer treatment for bypassing apoptosis to enhance the undermined therapeutic efficacy triggered by apoptosis resistance. A variety of anticancer drugs, synthesized compounds and natural products have been proven recently to induce non-apoptotic cell death and exhibit excellent anti-tumor effects. Moreover, the convergence of nanotechnology with functional materials and biomedicine science has provided tremendous opportunities to construct non-apoptotic cell death-based nanomedicine for innovative cancer therapy. Nanocarriers are not only employed in targeted delivery of non-apoptotic inducers, but also used as therapeutic components to induce non-apoptotic cell death to achieve efficient tumor treatment. This review first introduces the main characteristics, the mechanism and various pharmacological modulators of different non-apoptotic cell death forms, including ferroptosis, necroptosis, pyroptosis, autophagy, paraptosis, lysosomal-dependent cell death, and oncosis. Second, we comprehensively review the latest progresses of nanomedicine that induces various forms of non-apoptotic cell death and focus on the nanomedicine targeting different pathways and components. Furthermore, the combination therapies of non-apoptotic cell death with photothermal therapy, photodynamic therapy, immunotherapy and other modalities are summarized. Finally, the challenges and future perspectives in this regard are also discussed., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

A Gram-stain-negative, non-motile and aerobic bacterium, designated HHU G3-2 T , was isolated from surface water of the Yellow Sea, PR China. Strain HHU G3-2 T was positive for oxidase activity and negative for catalase. Optimal growth occurred at 28 °C (range, 20-37 °C), pH 7.0 (range, pH 6.0-9.0) and in the presence of 2-5 % (w/v) NaCl (range, 1-7%). Phylogenetic analysis based on 16S rRNA gene sequences and 120 ubiquitous single-copy protein-coding genes indicated that strain HHU G3-2 T formed a distinct phylogenetic lineage with Aestuariicella hydrocarbonica JCM 30134 T , sharing a 16S rRNA gene sequence similarity of 98.05%. Average nucleotide identity and digital DNA-DNA hybridization values between strain HHU G3-2 T and A. hydrocarbonica JCM 30134 T were 75.74 and 17.80%, respectively, which were below the threshold values of 95-96 and 70 %, respectively. The DNA G+C content of the genomic DNA was 51.17 mol%. The major fatty acids (>10 %) were C 17 : 1 ω 8 c (19.8 %), summed feature 3 (C 16 : 1 ω 7 c /C 16 : 1 ω 6 c ; 15.9 %), summed feature 8 (C 18 : 1 ω 7 c /C 18 : 1 ω 6 c ; 13.8 %) and C 17 : 0 (10.3 %). The predominant isoprenoid quinone was ubiquinone-8. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Based on the polyphasic taxonomic data, strain HHU G3-2 T represents a novel species of the genus Aestuariicella , for which the name Aestuariicella albida sp. nov. is proposed. The type strain is HHU G3-2 T (=MCCC 1K04224 T =JCM 34652 T =GDMCC 1.2418 T =CGMCC 1.17397 T ). In addition, we proposed the genus Aestuariicella as a member of the family Cellvibrionaceae .

Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF12.5%, TKPF25% and TKPF50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Such gene vectors exhibited the following features: (1) fluorination reduced the positive charge density and endowed hydrophobic and lipophobic characteristics to resist serum interactions; (2) The fluorophilic effect mediated efficient cellular uptake and endosomal escape; (3) ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. Notably, TKPFs also exhibited great serum resistance in gene delivery and TKPF50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrates that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.

The risk of chronic hepatitis B (CHB) infection is often affected by polyunsaturated fatty acids (PUFAs) metabolism which is strongly influenced by single nucleotide polymorphisms (SNPs) within the PUFA metabolic pathway. Given this, we designed this study to determine the relationship between specific polymorphisms within fatty acid desaturase 2 (FADS2), a key enzyme in PUFA metabolism, and CHB infection. We completed this evaluation using a case-control study comprising 230 CHB patients and 234 unrelated healthy controls in which the genetic relationships between three previously identified SNPs, isolated via mass spectrometry, and CHB infection. Our data revealed that none of these three SNPs (rs174568, rs174601, and rs2727270) were significantly associated with susceptibility to CHB infection when compared to healthy controls. However, when we stratified our cohort by sex, male subjects with the TC genotype for FADS2 exhibited a decreased risk for CHB infection (OR = 0.62, 95%CI = 0.39-0.96; OR = 0.64, 95%CI = 0.41-1.00; OR = 0.57, 95%CI = 0.36-0.90). Furthermore, age stratification revealed that both the T allele and the TC genotypes for each of the three target SNPs were less common in Chinese CHB cases in people younger than 50 years old. Correlation analysis also revealed that there was no statistically significant relationship between these three SNPs and HBV-DNA replication or hepatitis B surface antigen (HBsAg) levels. Thus, our data suggests that rs174568, rs174601, and rs2727270 may affect the CHB outcomes in various age or sex subgroups, suggesting that they may be useful predictive or diagnostic biomarkers of CHB infection in some populations., (Copyright © 2022. Published by Elsevier B.V.)

Background and Aims: Hepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear., Approach and Results: RNF5 expression was significantly down-regulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression of cell lines were subjected to hypoxia-reoxygenation challenge. Results showed that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, whereas RNF5 overexpression had the opposite effect. Furthermore, hepatocyte-specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage and cell apoptosis and activated hepatic inflammatory responses, whereas hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with phosphoglycerate mutase family member 5 (PGAM5) and mediated the degradation of PGAM5 through K48-linked ubiquitination, thereby inhibiting the activation of apoptosis-regulating kinase 1 (ASK1) and its downstream c-Jun N-terminal kinase (JNK)/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR., Conclusions: We revealed that RNF5 protected against HIR through its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR., (© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

A novel bacterium, designated strain XHP0097 T , was isolated from the surface water of the Yellow Sea, China. The cells were Gram-stain-negative, aerobic, rod-shaped, yellow-colored, and non-motile on 2216E agar. Optimal growth of strain XHP0097 T occurs at 28 °C and pH 7.0 with the presence of NaCl concentration 2% (w/v). According to the analysis of comparative 16S rRNA gene sequence, strain XHP0097 T showed the highest 16S rRNA gene sequence similarity with Sphingopyxis panaciterrulae KCTC 22112 T (98.2%). Phylogenetic analysis based on 16S rRNA gene sequences as well as on 120 ubiquitous single-copy protein-coding genes supported that strain XHP0097 T formed a distinct phyletic lineage as a new species within the genus Sphingopyxis. Strain XHP0097 T showed an average nucleotide identity value and a digital DNA-DNA hybridization (dDDH) of 79.1-81.7% and 21.9-24.4% to the members of the genus Sphingopyxis, respectively. According to genome sequence, the DNA G + C content of XHP0097 T was 64.8%. The major fatty acids (>10%) were C 16:0 (17.5%), summed feature 3 (C 16:1 ω7c and/or C 16:1 ω6c) (15.1%), and summed feature 8 (C 18:1 ω7c and/or C 18:1 ω6c) (19.2%). The major polar lipids of strain XHP0097 T were phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), and sphingoglycolipid (SGL). Q-10 was the predominant respiratory quinone. Characteristics of physiological and biochemical, phylogenetic, and chemotaxonomic analysis demonstrated the isolate XHP0097 T represents a novel species of the genus Sphingopyxis, for which the name Sphingopyxis jiangsuensis sp. nov. is proposed. The type strain is XHP0097 T (=MCCC 1K05845 T  = GDMCC 1.2415 T  = JCM 34678 T )., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hair conditions, such as hair loss and graying, are prevalent human conditions. But they are often poorly controlled due to our insufficient understanding of human scalp hair follicle (hsHF) in health and disease. Here we describe a comprehensive single-cell RNA-seq (scRNA-seq) analysis on highly purified black and early-stage graying hsHFs. Based on these, a concise single-cell atlas for hsHF and its early graying changes is generated and verified using samples from multiple independent individuals. These data reveal the lineage trajectory of hsHF in unprecedented detail and uncover its multiple unexpected features not found in mouse HFs, including the presence of an innerbulge like compartment in the growing phase, lack of a discrete companion layer, and enrichment of EMT features in HF stem cells (HFSCs). Moreover, we demonstrate that besides melanocyte depletion, early-stage human hair graying is also associated with specific depletion of matrix hair progenitors but not HFSCs. The hair progenitors' depletion is accompanied by their P53 pathway activation whose pharmaceutical blockade can ameliorate hair graying in mice, enlightening a promising therapeutic avenue for this prevalent hair condition., (© 2022. The Author(s).)

Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated by cohesin and CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale and to what extent fine-scale regulatory interactions depend on loop extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, which has enabled us to generate the most detailed local interaction data to date (20 bp resolution) and precisely investigate the effects of cohesin and CTCF depletion on chromatin architecture. Our data reveal that cis-regulatory elements have distinct internal nano-scale structures, within which local insulation is dependent on CTCF, but which are independent of cohesin. In contrast, we find that depletion of cohesin causes a subtle reduction in longer-range enhancer-promoter interactions and that CTCF depletion can cause rewiring of regulatory contacts. Together, our data show that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression., (© 2022. The Author(s).)

The past five decades have seen significant progress in our understanding of human hematopoiesis. This has in part been due to the unprecedented development of advanced technologies, which have allowed the identification and characterization of rare subsets of human hematopoietic stem and progenitor cells and their lineage trajectories from embryonic through to adult life. Additionally, surrogate in vitro and in vivo models, although not fully recapitulating human hematopoiesis, have spurred on these scientific advances. These approaches have heightened our knowledge of hematological disorders and diseases and have led to their improved diagnosis and therapies. Here, we review human hematopoiesis at each end of the age spectrum, during embryonic and fetal development and on aging, providing exemplars of recent progress in deciphering the increasingly complex cellular and molecular hematopoietic landscapes in health and disease. This review concludes by highlighting links between chronic inflammation and metabolic and epigenetic changes associated with aging and in the development of clonal hematopoiesis.

Background: Myocardial infarction is one of the most common types of coronary heart disease. It is mainly caused by the rupture of coronary atherosclerotic plaque, which leads to platelet agglutination and thrombosis. The occlusion of coronary arteries and vessels leads to insufficient myocardial blood supply, subsequently causing cardiac interstitial fibrosis, gradual enlargement of ventricles, and heart failure, which affects the quality of life and safety of patients., Aim: To investigate the effects of emergency percutaneous interventional therapy (PCI) and delayed stenting in acute myocardial infarction with high thrombotic load and identify factors related to major adverse cardiovascular events (MACE)., Methods: A total of 164 patients with acute myocardial infarction and high thrombotic load who received PCI were included. Of them, 92 patients were treated with delayed stent implantation (delayed group) and 72 patients received emergency PCI (immediate group). Myocardial perfusion after stent implantation was compared between the two groups. Patients were followed up for 12 mo, and the occurrence of MACE was used as the endpoint. Univariate and multivariate models were used to analyze the factors affecting MACE occurrence., Results: After stent implantation, 66 (71.74%) patients in the delayed group and 40 (55.56%) patients in the immediate group had thrombolysis in myocardial infarction (TIMI) flow grade 3 ( P < 0.05), while 61 (66.30%) patients in the delayed group and 39 (54.17%) patients in the immediate group reached TIMI myocardial perfusion grade 3 ( P > 0.05). MACE occurred in 29 patients. There were statistically significant differences between the MACE and non-MACE groups in diabetes rate, TIMI grading, stent implantation timing, intraoperative use of tirofiban, and the levels of white blood cells (WBC), neutrophils, red blood cell distribution width (RDW), and uric acid, and high-sensitivity C-reactive protein (hs-CRP) at admission ( P < 0.05). Logistic regression analysis showed that TIMI grade 3 and intraoperative use of tirofiban effectively reduced the risk of MACE ( P < 0.05), while immediate stent implantation, increased WBC, hs-CRP and RDW on admission increased the risk of MACE ( P < 0.05)., Conclusion: Delayed stent implantation outweighs emergency PCI in improving postoperative myocardial perfusion in acute myocardial infarction with high thrombotic load, and effectively reduces MACE in these patients., Competing Interests: Conflict-of-interest statement: No conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ferroptosis is a newly discovered non-apoptotic cell death form but its therapeutic efficacy triggered by traditional iron-based nanomaterials or classic drug inducers has been far from satisfactory due to the high glutathione (GSH) level in cancer cells and insufficient lipid peroxide production. Here we reported a ferroptosis/apoptosis combinational therapy by depleting GSH and downregulating GPX4 to disrupt redox homeostasis and amplify ferroptosis-related oxidation effect. In this study, we developed reactive oxygen species (ROS)-responsive serum-resistant nanoparticles with thioketal-crosslinked fluorinated polyethyleneimine 1.8K ( TK PF) as the core, which were wrapped with hyaluronic acid (HA) as the shell ( TK PFH NP) to co-deliver shGPX4 and shMTHFD2 plasmids for cancer treatment. The highly efficient and tumor-selective gene carrier TK PFH NPs revealed outstanding transfection efficiency (∼100 %) and sustained the efficiency (∼50 %) even in media containing 90 % FBS. Mediated by HA, TK PFH NPs actively targeted CD44 receptors, thus enabling efficient uptake by tumor cells and experiencing surface charge conversion to induce subsequent lysosomal escape. Then the TK PF NPs were effectively disintegrated by the abundant ROS in cancer cells, which facilitated the release of plasmids and avoided the cytotoxicity of cationic polymers. shGPX4 plasmid induced ferroptosis by producing ROS and lipid peroxides via downregulating GPX4, while shMTHFD2 triggered apoptosis by modulating NADPH/NADP and depleting GSH of the cancer cells. Moreover, GSH consumption caused by shMTHFD2 indirectly suppressed GPX4 and further augmented ferroptosis, showing synergistic anticancer effect against B16-F10 cells. Taken together, the rationally designed dual-gene loaded TK PFH NPs provided a safe and high-performance platform for enhanced ferroptosis-apoptosis combined anticancer efficacy based on gene therapy. STATEMENT OF SIGNIFICANCE: The therapeutic efficacy of ferroptosis has been far from satisfactory due to high GSH level and insufficient lipid peroxide production in cancer cells. Herein, we reported a ferroptosis/apoptosis combinational therapy by depleting GSH and downregulating GPX4 to disrupt redox homeostasis and amplify ferroptosis-related oxidation effect. ROS-responsive serum-resistant nanoparticles were fabricated with thioketal-crosslinked fluorinated PEI 1.8K ( TK PF) as the core and hyaluronic acid (HA) as the shell ( TK PFH NP) to co-deliver shGPX4 and shMTHFD2 plasmids. The shGPX4 plasmid induced ferroptosis by producing ROS and lipid peroxides via downregulating GPX4, while shMTHFD2 triggered apoptosis by modulating NADPH/NADP and depleting GSH. The rationally designed dual-gene loaded TK PFH NPs provided a safe and high-performance platform aimed for enhanced ferroptosis-apoptosis combined anticancer efficacy., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Hospital logistics staff comprise a crucial, albeit easily overlooked, group in the prevention and control of hospital nosocomial infections, especially during the COVID-19 pandemic. From the perspective of hospital safety improvement, this paper describes the current situation and challenges in the prevention and control of nosocomial infections among hospital logistics staff. We also provide the following suggestions to improve nosocomial infections: (1) updating the learning system of nosocomial infections, (2) reinforcing the training of infections prevention, (3) properly arranging manpower and resources, and (4) improving the supervision and management system., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Zhang Honghui et al.)

Asthma is an important cause of subacute cough. The concentration of alveolar nitric oxide (CANO) is a sensitive inflammatory indicator in peripheral airways, and it has received much less attention than the fraction of exhaled nitric oxide (FeNO 50 ). The main objective of this study was to explore the correlation between CANO and clinical parameters in asthmatic and non-asthmatic subacute cough, which might promote understanding of the clinical utility of CANO in these special patient populations. 155 patients with subacute cough were included consecutively, of which 25 were diagnosed as asthmatic. Data for demographic characteristics, FeNO 50 , CANO, baseline spirometry, bronchial provocation test (or bronchodilation test) and response dose ratio (RDR) were collected. Differences between the asthmatic and non-asthmatic groups were analyzed. Spearman's correlation coefficient ( ρ ) was used to evaluate the correlation between FeNO 50 , CANO and other clinical parameters. In patients with subacute cough, baseline CANO values did not differ between asthmatic and non-asthmatic patients (4.4(1.3, 11.4) versus 4.0(2.1, 6.8) ppb, P > 0.05). Besides, CANO exhibited a stronger association with pulmonary function parameters when compared with FeNO 50 . For asthmatic subacute cough, CANO was inversely correlated with FEV 1 /FVC ( ρ = -0.69, P < 0.01) and small airway parameters including MEF25 ( ρ = -0.47, P < 0.05) and MMEF ( ρ = -0.45, P < 0.05). For non-asthmatic subacute cough, CANO was inversely correlated with MEF25 ( ρ = -0.19, P < 0.05) and RDR ( ρ = -0.21, P < 0.05). In subacute cough, asthmatic and non-asthmatic patients had similar values of baseline CANO. In both asthmatic and non-asthmatic subacute cough, CANO exhibited a stronger association with pulmonary function parameters when compared with FeNO 50 . A low CANO value in non-asthmatic subacute cough corresponded to a higher value of RDR, which implied a stronger tendency towards airway responsiveness., (© 2021 IOP Publishing Ltd.)

Self-trapped excitons (STEs) have recently been observed in several metal halide perovskites (MHPs), especially in low-dimensional ones. Despite studies that have shown that factors like dopant, chemical composition, lattice distortion, and structural and electronic dimensionality may all affect the self-trapping of excitons, a general understanding of their mechanism of formation in MHPs is lacking. Here, we study the intrinsic and defect-induced self-trapping of excitons in three-, two-, and one-dimensional MHPs. We find that whether the free excitons could be trapped is simply determined by the competition of the energy-gap decrease and deformation-energy increase along with the lattice distortion. Both introducing halogen defects into the lattice and decreasing the dimensionality can tip the balance between them and thus facilitate the self-trapping of free excitons. This general picture of the mechanism of formation of STEs provides important insights into the design and development of high-performance white-light devices and solar cells with MHPs.

The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) disease (COVID-19) pandemic has caused millions of deaths worldwide. Genome-wide association studies identified the 3p21.31 region as conferring a twofold increased risk of respiratory failure. Here, using a combined multiomics and machine learning approach, we identify the gain-of-function risk A allele of an SNP, rs17713054G>A, as a probable causative variant. We show with chromosome conformation capture and gene-expression analysis that the rs17713054-affected enhancer upregulates the interacting gene, leucine zipper transcription factor like 1 (LZTFL1). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID-19 shows the presence of signals associated with epithelial-mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1. We conclude that pulmonary epithelial cells undergoing EMT, rather than immune cells, are likely responsible for the 3p21.31-associated risk. Since the 3p21.31 effect is conferred by a gain-of-function, LZTFL1 may represent a therapeutic target., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: High intrarenal pressure (IRP) during flexible ureteroscopy (FURS) may lead to severe complications. Reported methods for measuring IRP are often inconvenient to use, expensive and involve instruments that occupy the narrow ureter., Methods: We proposed an irrigation system, which can noninvasively estimate IRP based on the principle of fluid mechanics. To determine the feasibility of our system, we conducted irrigation experiments on a kidney phantom and a porcine kidney. The estimated IRPs were compared with the ground truth IRPs., Results: When no surgical instrument was inserted into the flexible ureteroscope's working channel, our system can estimate IRP with high accuracy. When a surgical instrument was inserted, our system can approximately estimate the level of IRP., Conclusions: Our proposed irrigation system can noninvasively estimate IRP, presenting a new thought for clinical practice. In future studies, in vivo experiments are needed to further validate and improve the system., (© 2021 John Wiley & Sons Ltd.)

Human hematopoiesis is a dynamic process that starts in utero 18-21 days post-conception. Understanding the site- and stage-specific variation in hematopoiesis is important if we are to understand the origin of hematological disorders, many of which occur at specific points in the human lifespan. To unravel how the hematopoietic stem/progenitor cell (HSPC) compartment changes during human ontogeny and the underlying gene regulatory mechanisms, we compare 57,489 HSPCs from 5 different tissues spanning 4 developmental stages through the human lifetime. Single-cell transcriptomic analysis identifies significant site- and developmental stage-specific transitions in cellular architecture and gene regulatory networks. Hematopoietic stem cells show progression from cycling to quiescence and increased inflammatory signaling during ontogeny. We demonstrate the utility of this dataset for understanding aberrant hematopoiesis through comparison to two cancers that present at distinct time points in postnatal life-juvenile myelomonocytic leukemia, a childhood cancer, and myelofibrosis, which classically presents in older adults., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Regressive changes in epithelial stem cells underlie mammalian skin aging, but the driving mechanisms are not well understood. Here, we report that mouse skin hair follicle stem cell (HFSC) aging is initiated by their intrinsic upregulation of miR-31, a microRNA that can be induced by physical injury or genotoxic stress and is also strongly upregulated in aged human skin epithelium. Using transgenic and conditional knockout mouse models plus a lineage-tracing technique, we show that miR-31 acts as a key driver of HFSC aging by directly targeting Clock, a core circadian clock gene whose deregulation activates a MAPK/ERK cascade to induce HFSC depletion via transepidermal elimination. Notably, blocking this pathway by either conditional miR-31 ablation or clinically approved MAPK/ERK inhibitors provides safe and effective protection against skin aging, enlightening a promising therapeutic avenue for treating skin aging and other genotoxic stress-induced skin conditions such as radiodermatitis., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, the most common single gene disorders. Here, we address mechanisms regulating the embryonically expressed α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, the ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) of open, acetylated chromatin and interacts with the α-globin super-enhancer. By contrast, in adult erythroid cells, the ζ-gene is packaged within a small (~10 kb) sub-domain of hypoacetylated, facultative heterochromatin within the acetylated sub-TAD and that it no longer interacts with its enhancers. The ζ-gene can be partially re-activated by acetylation and inhibition of histone de-acetylases. In addition to suggesting therapies for severe α-thalassemia, these findings illustrate the general principles by which reactivation of developmental genes may rescue abnormalities arising from mutations in their adult paralogues., (© 2021. The Author(s).)

In higher eukaryotes, many genes are regulated by enhancers that are 10 4 -10 6  base pairs (bp) away from the promoter. Enhancers contain transcription-factor-binding sites (which are typically around 7-22 bp), and physical contact between the promoters and enhancers is thought to be required to modulate gene expression. Although chromatin architecture has been mapped extensively at resolutions of 1 kilobase and above; it has not been possible to define physical contacts at the scale of the proteins that determine gene expression. Here we define these interactions in detail using a chromosome conformation capture method (Micro-Capture-C) that enables the physical contacts between different classes of regulatory elements to be determined at base-pair resolution. We find that highly punctate contacts occur between enhancers, promoters and CCCTC-binding factor (CTCF) sites and we show that transcription factors have an important role in the maintenance of the contacts between enhancers and promoters. Our data show that interactions between CTCF sites are increased when active promoters and enhancers are located within the intervening chromatin. This supports a model in which chromatin loop extrusion 1 is dependent on cohesin loading at active promoters and enhancers, which explains the formation of tissue-specific chromatin domains without changes in CTCF binding.

A Gram-stain-negative, aerobic, orange-pigmented bacterial strain, designated HHU K3-1  T , was isolated from the surface water of the Yellow Sea. The strain was observed to grow on 2216E agar medium, and growth occurred at pH 6.0-8.0 (optimum 7.0), 28-37 °C (optimum 28 °C), and in the presence of 0.5-5% (w/v) NaCl (optimum 1-3%). The major fatty acids (> 10%) were summed feature 3 (C 16:1 ω6c/C 16:1 ω7c), C 17:1 ω6c and summed feature 8 (C 18:1 ω6c/C 18:1 ω7c). Strain HHU K3-1  T was found to contain ubiquinone-10 as the predominant quinone and the major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG) and sphingoglycolipid (SGL). The 16S rRNA gene sequence analysis indicated that strain HHU K3-1  T shared highest similarities with Pelagerythrobacter marensis KCTC 22370  T (97.7%) and Qipengyuania oceanensis MCCC 1A09965 T (96.9%). However, a phylogenetic tree based on 288 orthologous clusters (OCs) indicated that HHU K3-1  T was close related to Parapontixanthobacter aurantiacus MCCC 1A09962 T . The pairwise AAI and evolutionary distance between HHU K3-1  T and Parapontixanthobacter aurantiacus MCCC 1A09962 T are 67.1% and 0.43, respectively, which meet the recently proposed standard to differentiate genera in the family Erythrobacteraceae. On the basis of the result obtained by the polyphasic taxonomic study, strain HHU K3-1  T can be considered to represent a novel genus in the family Erythrobacteraceae, for which the name Actirhodobacter atriluteus gen. nov., sp. nov. is proposed. The type strain is HHU K3-1  T (= MCCC 1K04225 T  = KCTC 72834  T  = CGMCC 1.17395  T ).

Background: Normothermic machine perfusion (NMP) could be beneficial for organ retrieval from donors after cardiac death (DCD). Activating transcription factor 6 (ATF6) was recently shown to mitigate liver ischemia/reperfusion injury and confer protection. The aims of this study were to assess the implication of ATF6 in liver retrieval from DCD rat livers with NMP and explore the effect of pharmacologic ATF-6 activation on liver retrieval. Methods: The livers from DCD rats were exposed to 30 min of warm ischemia and 8 h cold preservation followed by 2 h NMP with or without an ATF6 activator in the perfusate. Perfusates and livers were harvested to detect ATF6 expression, liver function, and inflammation. Results: DCD livers with NMP were associated with ATF6 overexpression and activation based on IHC and WB ( P < 0.05). The ATF6 activator downregulated perfusate aminotransferases, decreased the Suzuki score, downregulated CD68 and MPO based on IHC, induced the expression of cytochrome c in mitochondria and inhibited the expression of cytochrome c in cytoplasm based on WB, reduced TNFα and IL-6 levels based on ELISA, decreased levels of MDA, GSSG and ATP, and increased SOD activity and GSH levels in the perfused livers ( P < 0.05). Conclusion: ATF6 is important for liver retrieval, and an exogenous ATF6 activator accelerates liver retrieval from DCD rats in an ex vivo NMP model., 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 © 2021 Cheng, Shi, Jin, Shi, Liu, Zhang, Cao, Yang, Guo and Zhang.)

Maintaining a suitable level of sensitivity to environmental cues is crucial for proper function of adult stem cells. Here, we explore how the intrinsic sensitivity of skin hair follicle (HF) progenitors to growth stimuli is dynamically regulated. We discover miR-24 is an miRNA whose expression in HF progenitors inversely correlates with their growth potency in vivo. We show that its upregulation in adult skin epithelium leads to blunted responses of HF progenitors to growth cues and retards hair regeneration, while its conditional ablation leads to hyper-sensitized growth responsiveness of HF progenitors and precocious hair regeneration. Mechanistically, we find that miR-24 limits the intrinsic growth competence of HF progenitor by directly targeting Plk3, whose downregulation leads to reduced expression of CCNE1, a key cyclin for cell-cycle entry. These findings reveal an miRNA-mediated dynamic and cell-intrinsic mechanism used by HF progenitors to adapt their regenerative competence for different physiological conditions., Competing Interests: Declaration of interests A patent related to this work has been filed to China National Intellectual Property Administration with application number 202011112587.7. The authors declare no other competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Many established, but also potential future applications of NiTi-based shape memory alloys (SMA) in biomedical devices and solid-state refrigeration require long fatigue life with 10 7 -10 9 duty cycles 1,2 . However, improving the fatigue resistance of NiTi often compromises other mechanical and functional properties 3,4 . Existing efforts to improve the fatigue resistance of SMA include composition control for coherent phase boundaries 5-7 and microstructure control such as precipitation 8,9 and grain-size reduction 3,4 . Here, we extend the strategy to the nanoscale and improve fatigue resistance of NiTi via a hybrid heterogenous nanostructure. We produced a superelastic NiTi nanocomposite with crystalline and amorphous phases via severe plastic deformation and low-temperature annealing. The as-produced nanocomposite possesses a recoverable strain of 4.3% and a yield strength of 2.3 GPa. In cyclic compression experiments, the nanostructured NiTi micropillars endure over 10 8 reversible-phase-transition cycles under a stress of 1.8 GPa. We attribute the enhanced properties to the mutual strengthening of nanosized amorphous and crystalline phases where the amorphous phase suppresses dislocation slip in the crystalline phase while the crystalline phase hinders shear band propagation in the amorphous phase. The synergy of the properties of crystalline and amorphous phases at the nanoscale could be an effective method to improve fatigue resistance and strength of SMA.