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For large amounts of transition metal oxides, sulfides and carbon groups (IVA), the pulverization of electrode materials in lithium-ion batteries (LIBs) is always a serious and common problem due to volume expansion and stress accumulation resulting from phase transformation or alloying during the charge–discharge process, which leads to capacity fading and thus limits the cycling performance of LIBs. To solve these problems, conventionally, the rational design of electrode materials is needed. Here in this work, we report the synthesis of a novel anode material, hexagonal H4.5Mo5.25O18·(H2O)1.36 microrods (HMs) via a simple hydrothermal method. During the lithium-ion insertion/desertion process of the HMs, it was found that the HMs are first drastically transformed into Li2MoO4 nanotubes and then Li2MoO4 nanowire clusters embedded in amorphous sphere cages with a Li2O matrix, Mo metal and SEI thin film. Surprisingly, we discovered that the HMs exhibited extraordinary long-life cyclability with an unusual phenomenon: the specific capacity first decreased and then increased. The outstanding electrochemical performance could be explained by the formation of intermediate phase Li2MoO4 nanowires and amorphous sphere cages, which can maintain the lithium-ion paths and electronic transport, and prohibit the mechanical and chemical degradation of the electrode materials. The results show that the pulverization of the HM anode materials induced by lithium-ion insertion–extraction played a trigger role in the formation of a continuous pulverization film. Accordingly, a “damage-reconstruction” model based on ex situ XRD and FESEM analyses combined with ex situ XPS, FTIR and TEM characterizations of the charge–discharge process was proposed to explain such an unusual and intriguing finding. Compared with the conventional method for protecting electrode materials from pulverization, the robust continuous gel-like pulverization film containing a unique combination of intermediate phase and amorphous sphere cages provides a new insight into the mechanism for the extraordinary long-term cyclability of electrode materials. [ABSTRACT FROM AUTHOR]

Variability of urban fog during the last 50 years in Anhui Province (China) and its possible underlying mechanisms are analyzed based on daily meteorological records from 78 stations. The effects of urban development and aerosols on fog formation are discussed through an analysis of trends in fog frequency and comparison with a number of meteorological parameters, coal consumption and vehicle usage as indicators of economic development and aerosol production, and visibility as an indicator of aerosol load. The impact of urbanization on fog is different at various stages of urban development. The number of annual fog days in most cities studied has increased since the 1960s but decreased after the mid 1980s in large, old cities. New cities, on the other hand, are characterized by still increasing fog frequency. During the last thirty years, fog dissipation time occurred later, average fog duration increased and visibility decreased at most urban stations. The annual total coal combustion of Anhui Province correlates negatively with the average visibility within fog and average annual fog frequency in old cities. The difference in minimum temperature between cities and towns is negatively (positively) correlated with fog frequency in old (new) cities. Our study therefore supports previous findings that the number of fog days in cities is influenced by increased (i) temperatures associated with urban development and (ii) aerosol concentration due to urban development and industrial activity. [Copyright &y& Elsevier]

Osteoarthritis (OA) is marked by cartilage deterioration, subchondral bone changes, and an inflammatory microenvironment. The study introduces the Microneedle-Delivered Polydopamine-Exosome (PDA@Exo MN), a therapeutic that not only preserves cartilage and promotes bone regeneration but also improves localized drug delivery through enhanced penetration capabilities. PDA@Exo MN shows strong reactive oxygen species (ROS) scavenging abilities and high biocompatibility, fostering osteogenesis and balancing anabolic and catabolic processes in cartilage. It directs macrophage polarization from M0 to the anti-inflammatory M2 phenotype. RNA sequencing of treated chondrocytes demonstrates restored cellular function and activated antioxidant responses, with modulated inflammatory pathways. The PI3K-AKT-mTOR pathway's activation, essential for PDA@Exo's effects, is confirmed via bioinformatics and Western blot. In vivo assessments robustly validate that PDA@Exo MN prevents cartilage degradation and OA progression, supported by histological assessments and micro-CT analysis, highlighting its disease-modifying impact. The excellent biocompatibility of PDA@Exo MN, verified through histological (H&E) and blood tests showing no organ damage, underscores its safety and efficacy for OA therapy, making it a novel and multifunctional nanomedical approach in orthopedics, characterized by organ-friendliness and biosecurity., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Osteosarcoma is one of the most dreadful bone neoplasms in young people, necessitating the development of innovative therapies that can effectively eliminate tumors while minimizing damage to limb function. An ideal therapeutic strategy should possess three essential capabilities: antitumor effects, tissue-protective properties, and the ability to enhance osteogenesis. In this study, self-assembled Ce-substituted molybdenum blue (CMB) nanowheel crystals are synthesized and loaded onto 3D-printed bioactive glass (CMB@BG) scaffolds to develop a unique three-in-one treatment approach for osteosarcoma. The CMB@BG scaffolds exhibit outstanding photothermally derived tumor ablation within the near-infrared-II window due to the surface plasmon resonance properties of the CMB nanowheel crystals. Furthermore, the photothermally synergistic catalytic effect of CMB promotes the rapid scavenging of reactive oxygen species caused by excessive heat, thereby suppressing inflammation and protecting surrounding tissues. The CMB@BG scaffolds possess pro-proliferation and pro-differentiation capabilities that efficiently accelerate bone regeneration within bone defects. Altogether, the CMB@BG scaffolds that combine highly efficient tumor ablation, tissue protection based on anti-inflammatory mechanisms, and enhanced osteogenic ability are likely to be a point-to-point solution for the comprehensive therapeutic needs of osteosarcoma., (© 2024 Wiley‐VCH GmbH.)

Osteosarcoma, recognized for its aggressiveness and resistance to chemotherapy, notably doxorubicin, poses significant treatment challenges. This comprehensive study investigated the CXCR4-CARM1-YAP signaling axis and its pivotal function in controlling aerobic glycolysis, which plays a crucial role in doxorubicin resistance. Detailed analysis of Dox-resistant 143b/MG63-DoxR cells has uncovered the overexpression of CXCR4. Utilizing a combination of molecular biology techniques including gene silencing, aerobic glycolysis assays such as Seahorse experiments, RNA sequencing, and immunofluorescence staining. The study provides insight into the mechanistic pathways involved. Results demonstrated that disrupting CXCR4 expression sensitizes cells to doxorubicin-induced apoptosis and alters glycolytic activity. Further RNA sequencing revealed that CARM1 modulated this effect through its influence on glycolysis, with immunofluorescence of clinical samples confirming the overexpression of CXCR4 and CARM1 in drug-resistant tumors. Chromatin immunoprecipitation studies further highlighted the role of CARM1, showing it to be regulated by methylation at the H3R17 site, which in turn affected YAP expression. Crucially, in vivo experiments illustrated that CARM1 overexpression could counteract the tumor growth suppression that resulted from CXCR4 inhibition. These insights revealed the intricate mechanisms at play in osteosarcoma resistance to doxorubicin and pointed toward potential new therapeutic strategies that could target this metabolic and signaling network to overcome drug resistance and improve patient outcomes., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Alveolar echinococcosis is considered to be one of the most potentially lethal parasitic zoonotic diseases. However, the molecular mechanisms by which Echinococcus multilocularis interacts with hosts are poorly understood, hindering the prevention and treatment of this disease. Due to the great advantages of cell culture systems for molecular research, numerous attempts have been made to establish primary cell cultures for E. multilocularis. In this study we developed a simple, rapid, and economical method that allows E. multilocularis metacestode tissue blocks to generate daughter vesicles without the continuous presence of host feeder cells in a regular medium. We performed anaerobic, hypoxic (1% O2), normoxic, and semi-anaerobic (in sealed tubes) cultures and found that E. multilocularis metacestode tissues can produce daughter vesicles only in the sealed tubes after 4 wk of incubation. The daughter vesicles cultivated in this system were remarkably enlarged under anaerobic conditions after 8 days of culture, whereas vesicles cultured under hypoxic (1% O2) and normoxic conditions showed only a mild increase in volume. Our in vitro cultivated vesicles showed strong viability and could be used to test antiparasitic drugs, isolate primary cells, and infect animals., (© American Society of Parasitologists 2024.)

Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by infection with the larval stage of Echinococcus multilocularis and a major challenge to human public health. Vaccines are the most effective way to prevent and control infectious diseases. We previously revealed that the Echinocuccus granulosus recombinant protein P29 is a good vaccine candidate against E . granulosus . However, the protective and immunological mechanism of rEg.P29 against E . multilocularis remain unclear. In this study, CD4 + T cell-deficient mice are transferred with spleen CD4 + T cells isolated from wild-type mice and subjected to rEg.P29 immunization, and then these immunized mice are infected with E . multilocularis . The cyst inhibition rate is calculated by weighing the body and cyst weights. The level of antibody is detected by ELISA. Flow cytometry is used to detect the level of IFN-γ production by CD4 + T and CD8 + T cells. The cytokines in culture supernatant are detected by ELISA. The expressions of CD44 and CD62L on memory T cells are determined by flow cytometry. The results show the cyst inhibition rate is 41.52% after adoptive transfer of CD4 + T cells. Furthermore, the levels of IgG, IgM, IgA and IgE in serum are significantly increased compared with those in the PBS group. The IFN-γ-secretion by CD8 + T cells and the level of IFN-γ in culture supernatant are obviously increased; and the number of CD4 + T cells is increased, but the number of IFN-γ producing CD4 + T cells has no significant difference compared with PBS group. In addition, the number of CD44 + CD62L ‒ CD8 + memory T cells in the spleen is significantly increased, while the number of CD44 ‒ CD62L + CD8 + memory T cells is not significantly altered. Collectively, rEg.P29 can alleviate E . multilocularis infection by inducing humoral immune responses and CD8 + T cell responses.

Flexible and stretchable triboelectric nanogenerators (TENGs) have been rapidly advanced owing to the demand for portable and wearable electronic devices that can work under universal or motional circumstances. While versatile materials can be applied in a TENG as dielectric materials, flexible and cost-effective electrodes are crucially important for the output performance of TENGs. Herein, we developed a poly(vinyl alcohol) (PVA) hydrogel TENG doped with a novel two-dimensional material, graphitic carbon nitride (g-C 3 N 4 ), which could act as both a cost-effective flexible electrode and a positive dielectric for TENG with different morphologies. The measured peak-to-peak open-circuit voltage of the TENG reached 80 V at a dopant concentration of 2.7 wt % in single-electrode mode, which is far higher than that of the pristine PVA hydrogel TENG. As a demonstration of the application, the g-C 3 N 4 /PVA hydrogel TENG can be adopted as electronic skin to monitor the movement of the human body. Low-frequency mechanical energy-harvesting devices in different morphologies including discoid flake shape, tube shape, and spiral shape in the single-electrode mode or contact-separation mode have been designed, fabricated, and evaluated. All of these merits of the proposed hydrogel TENG after doping two-dimensional (2D) material g-C 3 N 4 have demonstrated their promising potential for versatile applications in biomechanical energy harvesting and self-powered sensing.

Photochromic materials with rapid color-switching, long color retention times, and rewritability are crucial for meeting the requirements of future rewritable ink-free media. However, these requirements are challenging to satisfy simultaneously due to the inherent constraints among these features. Herein, a novel photochromic nanofiber nonwoven fabric was designed and constructed based on a conjugated organic-inorganic hybrid structure through electrospinning and hot-pressing techniques. The as-prepared fabric can change color in merely 5 s under UV irradiation and can reach saturation within 2 min. In addition, upon the introduction of a potent metal chelator, its color retention time exceeds 14 days under ambient conditions, significantly longer than that of most rewritable materials recently reported (several hours to 5 days). Moreover, the fabric exhibits high writing resolution and can be photoprinted and heat-erased for over 100 cycles while still retaining 96% of its initial reflectivity. Hydrophobic thermoplastic polyurethane provides the fabric with excellent waterproof and antifouling properties, thus preventing the composite from swelling or collecting graffiti due to moisture or dust. This work exploits a competitive approach for designing flexible, rewritable, and superior functional wearables with practical applications.

Achieving flexible electronics with comfort and durability comparable to traditional textiles is one of the ultimate pursuits of smart wearables. Ink printing is desirable for e-textile development using a simple and inexpensive process. However, fabricating high-performance atop textiles with good dispersity, stability, biocompatibility, and wearability for high-resolution, large-scale manufacturing, and practical applications has remained challenging. Here, water-based multi-walled carbon nanotubes (MWCNTs)-decorated liquid metal (LM) inks are proposed with carbonaceous gallium-indium micro-nanostructure. With the assistance of biopolymers, the sodium alginate-encapsulated LM droplets contain high carboxyl groups which non-covalently crosslink with silk sericin-mediated MWCNTs. E-textile can be prepared subsequently via printing technique and natural waterproof triboelectric coating, enabling good flexibility, hydrophilicity, breathability, wearability, biocompatibility, conductivity, stability, and excellent versatility, without any artificial chemicals. The obtained e-textile can be used in various applications with designable patterns and circuits. Multi-sensing applications of recognizing complex human motions, breathing, phonation, and pressure distribution are demonstrated with repeatable and reliable signals. Self-powered and energy-harvesting capabilities are also presented by driving electronic devices and lighting LEDs. As proof of concept, this work provides new opportunities in a scalable and sustainable way to develop novel wearable electronics and smart clothing for future commercial applications., (© 2024. The Author(s).)

Background: Osteoarthritis (OA) is a degenerative joint disease that affects millions worldwide. Synovitis and macrophage polarization are important factors in the development of OA. However, the specific components of synovial fluid (SF) responsible for promoting macrophage polarization remain unclear., Methods: Semi-quantitative antibody arrays were used to outline the proteome of SF. Differential expression analysis and GO/KEGG were performed on the obtained data. Immunohistochemistry and ELISA were used to investigate the relationship between SF S100A12 levels and synovitis levels in clinalclinical samples. In vitro cell experiments were conducted to investigate the effect of S100A12 on macrophage polarization. Public databases were utilized to predict and construct an S100A12-centered lncRNA-miRNA-mRNA competing endogenous RNA network, which was preliminarily validated using GEO datasets., Results: The study outlines the protein profile in OA and non-OA SF. The results showed that the S100A12 level was significantly increased in OA SF and inflammatory chondrocytes. The OA synovium had more severe synovitis and higher levels of S100A12 than non-OA synovium. Exogenous S100A12 upregulated the levels of M1 markers and phosphorylated p65 and promoted p65 nuclear translocation, while pretreatment with BAY 11-7082 reversed these changes. It was also discovered that LINC00894 was upregulated in OA and significantly correlated with S100A12, potentially regulating S100A12 expression by acting as a miRNA sponge., Conclusions: This study demonstrated that S100A12 promotes M1 macrophage polarization through the NF-κB pathway, and found that LINC00894 has the potential to regulate the expression of S100A12 as a therapeutic approach.

Background: To investigate whether accurate placement of sustentaculum tali screws have the impacts on the clinical efficacy of calcaneal fractures., Methods: A retrospective analysis of 72 cases (73 feet) of calcaneal fractures from September 2015 to September 2019 treated with open reduction and internal fixation with sustentaculum tali screws was conducted. Patients were divided into the sustentaculum tali fixation group (ST group) and the sustentaculum fragment fixation group (STF group) according to the location of the sustentaculum tali screw placement. The functional outcomes at preoperative, 7 days and 1 year postoperative were collected and analyzed., Results: In the ST group (40 feet), the Gissane's angle altered from (109.89 ± 12.13)° to (121.23 ± 9.34)° and (119.08 ± 8.31)° at 7 days and 1 year postoperative, respectively. For Böhler's angles altered from (11.44 ± 5.94)°, to (31.39 ± 7.54)°, and (30.61 ± 7.94)° at 7 days and 1 year postoperative, respectively. In the STF group (33 feet), Gissane's angle altered from (110.47 ± 14.45)°, to (122.08 ± 8.84)°, and (120.67 ± 9.07)° and Böhler's angle altered from (11.32 ± 6.77)°, to (28.82 ± 8.52)°, and (28.25 ± 9.13)° (P < 0.001). However, there was no statistically significant difference in functional outcomes at 1 week after surgery and 1 year after surgery (P > 0.05). The AOFAS scores at the final follow-up of the two groups: ST group (88.95 ± 6.16) and STF group (89.78 ± 8.76); VAS scores, ST group (0.83 ± 0.98) and STF group (1.03 ± 1.59), all differences were not statistically significant (P > 0.05)., Conclusion: The position of sustentaculum tali screws has no significant difference on the short-term clinical outcome in patients with calcaneal fractures, while reliable fixation of screws to sustentaculum tali fragment can achieve similar clinical outcome., (© 2024. The Author(s).)

Background: Alveolar echinococcosis (AE) can cause severe liver injury and be fatal if left untreated. Currently, there are no effective therapeutic options for AE-induced liver injury. Therefore, by exploring the changes of gene proteins in mice with damaged liver, we attempted to identify the key molecules of liver damage, and provide data that will enable the development of drugs targeting hepatic AE., Methods: BALB/c mice were inoculated with protoscoleces via the hepatic portal vein. Three months later, B-ultrasound examination and Hematoxylin-eosin (H&E) staining were used to confirm liver damage in mice. RNA sequencing and Liquid chromatography-mass spectrometry (LC-MS) were used to screen differentially expressed molecules associated with liver damage through bioinformatics, and Quantitative Real-Time PCR (qRT-PCR) was used to verify their expression., Results: B-ultrasound examination showed liver lesions in the infected group, and H&E staining showed liver inflammation, fibrosis and liver necrosis. RNA sequencing and LC-MS results showed changes in the levels of more than 1000 genes and proteins, with upregulation of immune and inflammation pathways. By contrast, the downregulated genes and proteins were mostly involved in various metabolic reactions. Correlation analysis was conducted between the transcriptome data and proteome data. The results revealed 240 differentially expressed genes, of which 192 were upregulated, and 48 were downregulated. Many of these genes were involved in metabolic reactions, such as Catalase (Cat), fatty acid synthase (Fasn), and IL-16 genes, which may have relevance to liver injury. The results of qRT-PCR were consistent with those of bioinformatics analysis., Conclusions: The mechanisms of liver injury in mice infected with Echinococcus multilocularis are complex, involving abnormal metabolism, oxidative stress, inflammatory response, and many other factors. This study provides the data for preliminary exploration for the development of targeted therapies against AE., Competing Interests: Declaration of Competing Interest 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The role of follicular T helper (Tfh) cells in humoral response has been considered essential in recent years. Understanding how Tfh cells control complex humoral immunity is critical to developing strategies to improve the efficacy of vaccines against SARS-CoV-2 and other emerging pathogens. However, the immunologic mechanism of Tfh cells in SARS-CoV-2 receptor binding domain (RBD) vaccine strategy is limited. In this study, we expressed and purified recombinant SARS-CoV-2 RBD protein in Drosophila S2 cells for the first time and explored the mechanism of Tfh cells induced by RBD vaccine in humoral immune response. We mapped the dynamic of Tfh cell in lymph node and spleen following RBD vaccination and revealed the relationship between Tfh cells and humoral immune response induced by SARS-CoV-2 RBD vaccine through correlation analysis, blocking of IL-21 signaling pathway, and co-culture of Tfh with memory B cells. Recombinant RBD protein elicited a predominant Tfh1 and Tfh1-17 subset response and strong GC responses in spleen and lymph nodes, especially to enhanced vaccination. IL-21 secreted by Tfh cells affected the development and differentiation of B cells and played a key role in the humoral immune response. These observations will help us further understand the mechanism of protective immune response induced by COVID-19 vaccine and has guiding significance for the development of vaccines against newly emerging mutants., (© 2023. Sichuan International Medical Exchange & Promotion Association.)

Purpose: Arthroscopic superior capsule reconstruction (SCR) with the long head of the biceps (LHBT) was performed to restore structural stability, force couple balance, and shoulder joint function. This study aimed to evaluate the functional outcomes of SCR using the LHBT over at least 24 months of follow-up., Method: This retrospective study included 89 patients with massive rotator cuff tears who underwent SCR using the LHBT, met the inclusion criteria and underwent follow up for at least 24 months. The preoperative and postoperative shoulder range of motion (forward flexion, external rotation, and abduction), acromiohumeral interval (AHI), visual analog scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score and Constant-Murley score were obtained, and the tear size, and Goutallier and Hamada grades were also investigated., Results: Compared with those measured preoperatively, the range of motion, AHI, and VAS, Constant-Murley, and ASES scores were significantly improved immediately postoperatively (P < 0.001) and at the 6-month, 12-month, and final follow-ups (P < 0.001). At the last follow-up, the postoperative ASES score and Constant-Murley score increased from 42.8 ± 7.6 to 87.4 ± 6.1, and 42.3 ± 8.9 to 84.9 ± 10.7, respectively; with improvements of 51 ± 21.7 in forward flexion, 21.0 ± 8.1 in external rotation, and 58.5 ± 22.5 in abduction. The AHI increased 2.1 ± 0.8 mm and the VAS score significantly changed from 6.0 (5.0, 7.0) to 1.0 (0.0, 1.0), at the final follow-up. Eleven of the 89 patients experienced retears, and one patient needed reoperation., Conclusion: In this study with at least 24-months of follow-up, SCR using the LHBT for massive rotator cuff tears could effectively relieve shoulder pain, restore shoulder function and increase shoulder mobility to some extent., Level of Evidence: IV., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Background: Different subtypes of dendritic cells (DCs) can induce different types of immune responses. Our previous study found that Echinococcus granulosus (E. granulosus) antigens (Eg.ferritin, Eg.mMDH and Eg.10) stimulated DC differentiation to different subtypes and produced different immune responses., Objective: To further understand whether Eg.ferritin, Eg.mMDH and Eg.10 affect the DC-mediated immune response by promoting the differentiation of monocytes to DCs., Methods: Bone marrow-derived monocytes were exposed to three antigens of E. granulosus on days 0, 3, 5, and 7. The percentage of monocyte-derived DCs (moDCs), DCs subsets, and the expression of surface molecules of DCs at different time points in different groups were assessed by flow cytometry. The levels of cytokines of IL-1β, IL-4, IL-6, IL-10, IL-13, IFN-γ, TNF-α, IL-12p70, IL-18, IL-23, and IL-27 in the cell culture supernatant were detected by multi-factorial detection technology., Results: The percentage of moDCs revealed that none of the three antigens blocked monocyte differentiation to DCs. The monocytes of 7-day-old cultures showed increased sensitivity to these antigens. The Eg.ferritin induced more mature DCs, which expressed high levels of MHC II and costimulatory molecules, and secreted Th1 cytokines. Eg10 and Eg.mMDH induced lower degrees of DC maturation, however differentiated DCs were in a semi-mature state due to low expression of MHC II and costimulatory molecules and secretion of higher Th2 and lower Th1 cytokines., Conclusion: Eg.ferritin promotes full maturation of DCs and induces Th1 immune response, whereas Eg.10 and Eg.mMDH induce semi-mature DCs producing higher levels of Th2 cytokines.

Targeting histone deacetylase 6 (HDAC6) has emerged as a promising therapeutic approach for anti-inflammation and related biological pathways, including inflammatory events associated with the brain. In this study, in order to develop brain-permeable HDAC6 inhibitors for anti-neuroinflammation, we report here the design, synthesis, and characterization of a number of N-heterobicyclic analogues that can inhibit HDAC6 with high specificity and strong potency. Among our analogues, PB131 exhibits potent binding affinity and selectivity against HDAC6, with an IC 50 value of 1.8 nM and more than 116-fold selectivity over other HDAC isoforms. In addition, PB131 shows good brain penetration, binding specificity, and reasonable biodistribution through our positron emission tomography (PET) imaging studies of [ 18 F]PB131 in mice. Furthermore, we characterized the efficacy of PB131 on regulating neuroinflammation using the mouse microglia model BV2 cells in vitro and the LPS-induced inflammation mouse model in vivo. These data not only indicate the anti-inflammatory activity of our novel HDAC6 inhibitor PB131, but also strengthen the biological functions of HDAC6 and further extend the therapeutic approach inhibiting HDAC6. Our findings show that PB131 displays good brain permeability, high specificity, and strong potency toward inhibiting HDAC6 and is a potential HDAC6 inhibitor for inflammation-related disease treatment, especially neuroinflammation., 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 Masson SAS. All rights reserved.)

3-Hydroxybutyrate (3HB) is a small ketone body molecule produced endogenously by the body in the liver. Previous studies have shown that 3HB can reduce blood glucose level in type 2 diabetic (T2D) patients. However, there is no systematic study and clear mechanism to evaluate and explain the hypoglycemic effect of 3HB. Here we demonstrate that 3HB reduces fasting blood glucose level, improves glucose tolerance, and ameliorates insulin resistance in type 2 diabetic mice through hydroxycarboxylic acid receptor 2 (HCAR2). Mechanistically, 3HB increases intracellular calcium ion (Ca 2+ ) levels by activating HCAR2, thereby stimulating adenylate cyclase (AC) to increase cyclic adenosine monophosphate (cAMP) concentration, and then activating protein kinase A (PKA). Activated PKA inhibits Raf1 proto-oncogene serine/threonine-protein kinase (Raf1) activity, resulting in a decrease in extracellular signal-regulated kinases 1/2 (ERK1/2) activity and ultimately inhibiting peroxisome proliferator-activated receptor γ (PPARγ) Ser273 phosphorylation in adipocytes. Inhibition of PPARγ Ser273 phosphorylation by 3HB altered the expression of PPARγ regulated genes and reduced insulin resistance. Collectively, 3HB ameliorates insulin resistance in type 2 diabetic mice through a pathway of HCAR2/Ca 2+ /cAMP/PKA/Raf1/ERK1/2/PPARγ., (© 2023. The Author(s).)

Background: Long non-coding RNAs (lncRNAs) have been reported to have a crucial impact on the pathogenesis of acute myeloid leukemia (AML). Cuproptosis, a copper-triggered modality of mitochondrial cell death, might serve as a promising therapeutic target for cancer treatment and clinical outcome prediction. Nevertheless, the role of cuproptosis-related lncRNAs in AML is not fully understood., Methods: The RNA sequencing data and demographic characteristics of AML patients were downloaded from The Cancer Genome Atlas database. Pearson correlation analysis, the least absolute shrinkage and selection operator algorithm, and univariable and multivariable Cox regression analyses were applied to identify the cuproptosis-related lncRNA signature and determine its feasibility for AML prognosis prediction. The performance of the proposed signature was evaluated via Kaplan-Meier survival analysis, receiver operating characteristic curves, and principal component analysis. Functional analysis was implemented to uncover the potential prognostic mechanisms. Additionally, quantitative real-time PCR (qRT-PCR) was employed to validate the expression of the prognostic lncRNAs in AML samples., Results: A signature consisting of seven cuproptosis-related lncRNAs (namely NFE4, LINC00989, LINC02062, AC006460.2, AL353796.1, PSMB8-AS1, and AC000120.1) was proposed. Multivariable cox regression analysis revealed that the proposed signature was an independent prognostic factor for AML. Notably, the nomogram based on this signature showed excellent accuracy in predicting the 1-, 3-, and 5-year survival (area under curve = 0.846, 0.801, and 0.895, respectively). Functional analysis results suggested the existence of a significant association between the prognostic signature and immune-related pathways. The expression pattern of the lncRNAs was validated in AML samples., Conclusion: Collectively, we constructed a prediction model based on seven cuproptosis-related lncRNAs for AML prognosis. The obtained risk score may reveal the immunotherapy response in patients with this disease., (© 2023. The Author(s).)

Existing detection methods for pathogen nucleic acid detection, such as polymerase chain reaction (PCR), are complicated and expensive to perform. Here, we report a simple and versatile strategy for highly sensitive detection of pathogen nucleic acid based on toehold-mediated strand displacement initiated primer exchange amplification (t-PER). In the presence of the target, the blocked hairpin substrate is released by toehold-mediated strand displacement, which triggers the primer exchange reaction amplification. Then, multiple long tandem-repeat single-strands generated by PER open the molecular beacon to recover the fluorescence signal. The t-PER protocol also successfully directly detected human papilloma virus from clinical cervical swab samples, with consistent results compared to real time-polymerase chain reaction (RT-PCR). Moreover, the versatility and clinical feasibility of this method was further confirmed by measuring Epstein-Barr virus, hepatitis B virus, and Ureaplasma urealyticum from different clinical samples (serum samples and urine samples). This simple platform enabled specific and sensitive detection of pathogen nucleic acid in a format that might hold great potential for point-of-care infection diagnosis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Muscle atrophy is an increasingly global health problem affecting millions, there is a lack of clinical drugs or effective therapy. Excessive loss of muscle mass is the typical characteristic of muscle atrophy, manifesting as muscle weakness accompanied by impaired metabolism of protein and nucleotide. (D)-3-hydroxybutyrate (3HB), one of the main components of the ketone body, has been reported to be effective for the obvious hemodynamic effects in atrophic cardiomyocytes and exerts beneficial metabolic reprogramming effects in healthy muscle. This study aims to exploit how the 3HB exerts therapeutic effects for treating muscle atrophy induced by hindlimb unloaded mice., Results: Anabolism/catabolism balance of muscle protein was maintained with 3HB via the Akt/FoxO3a and the mTOR/4E-BP1 pathways; protein homeostasis of 3HB regulation includes pathways of ubiquitin-proteasomal, autophagic-lysosomal, responses of unfolded-proteins, heat shock and anti-oxidation. Metabolomic analysis revealed the effect of 3HB decreased purine degradation and reduced the uric acid in atrophied muscles; enhanced utilization from glutamine to glutamate also provides evidence for the promotion of 3HB during the synthesis of proteins and nucleotides., Conclusions: 3HB significantly inhibits the loss of muscle weights, myofiber sizes and myofiber diameters in hindlimb unloaded mouse model; it facilitates positive balance of proteins and nucleotides with enhanced accumulation of glutamate and decreased uric acid in wasting muscles, revealing effectiveness for treating muscle atrophy., (© 2022. The Author(s).)

Human body can obtain energy from either carbohydrate or fat digestion. Although glucose metabolism derived from carbohydrate-based diets has long been utilized for energy supply, it has been recently discovered that shifting from glucose to fatty acid metabolism may become a novel way for improving human health especially when carbohydrate is deprived. In recent years, intermittent fasting and ketogenic diets have received a lot of attention in respect to favoring fatty acid metabolism. In all cases, fatty acid metabolism produces D-β-hydroxybutyrate (D3HB), which is a natural ketone body, as well as, a monomer of microbial poly-D-β-hydroxybutyrate (PHB). D3HB can be utilized by different cells of the body as an alternative energy fuel or an intracellular signaling molecule with multiple downstream signaling pathways. Usually, the serum level of D3HB is increased during ketogenic diets, however, requires a very long period of adaptation (over 3-months) and exhibits unwanted adverse effects. Hence, exogenous ketone supplements using D3HB have become a more effective approach to induce and maintain nutritional ketosis for subsequent functional effects. This review describes how D3HB is produced and metabolized within the body, the functional roles played by D3HB, and a detailed summary of the different applications of exogenous ketones that have been explored to date in both nutritional and therapeutical context.

Corynebacterium glutamicum is a versatile chassis which has been widely used to produce various amino acids and organic acids. In this study, we report the development of an efficient C. glutamicum strain to produce 1,3-propanediol (1,3-PDO) from glucose and xylose by systems metabolic engineering approaches, including (1) construction and optimization of two different glycerol synthesis modules; (2) combining glycerol and 1,3-PDO synthesis modules; (3) reducing 3-hydroxypropionate accumulation by clarifying a mechanism involving 1,3-PDO re-consumption; (4) reducing the accumulation of toxic 3-hydroxypropionaldehyde by pathway engineering; (5) engineering NADPH generation pathway and anaplerotic pathway. The final engineered strain can efficiently produce 1,3-PDO from glucose with a titer of 110.4 g/L, a yield of 0.42 g/g glucose, and a productivity of 2.30 g/L/h in fed-batch fermentation. By further introducing an optimized xylose metabolism module, the engineered strain can simultaneously utilize glucose and xylose to produce 1,3-PDO with a titer of 98.2 g/L and a yield of 0.38 g/g sugars. This result demonstrates that C. glutamicum is a potential chassis for the industrial production of 1,3-PDO from abundant lignocellulosic feedstocks., (Copyright © 2022 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Inadequate immune response remains a critical cause of immunotherapy failure in various tumor treatments. Herein, we offer a new approach to achieve a cross-talk between innate and adaptive immune responses based on a new nanoplatform for photothermal therapeutics. The nanoplatform was formed by linking titanium carbide MXene with Mn 2+ -contained ovalbumin (OVA), where it can trigger efficient mt-DNA presentation and the release of OVA and Mn 2+ upon the irradiation of near-infrared laser. More importantly, the released mt-DNA and Mn 2+ synergistically activate innate immunity via the cGAS-stimulator of the interferon genes signaling pathway, and the OVA and protein antigens from tumor cells enhance adaptive immunity. Furthermore, in an osteosarcoma model, we observed that the proposed nanoplatform leads to the effective presentation of tumor antigens, which boost the maturation of dendritic cells (DCs) to the hilt and thus improve the infiltration of cytotoxic T lymphocyte in primary and distant tumors. Collectively, our work not only demonstrates a method for constructing a new nanoplatform for photothermal therapeutics but also provides a general strategy for synchronously activating innate and adaptive immunities to promote the maturation of DCs for antimetastasis tumor therapy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: To validate a competency-based assessment scale for students majoring in clinical medicine, ASK-SEAT. Students' competency growth across grade years was also examined for trends and gaps., Methods: Questionnaires were distributed online from May through August in 2018 to Year-2 to Year-6 students who majored in clinical medicine at the Shantou University Medical College (China). Cronbach alpha values were calculated for reliability of the scale, and exploratory factor analysis employed for structural validity. Predictive validity was explored by correlating Year-4 students' self-assessed competency ratings with their licensing examination scores (based on Kendall's tau-b values). All students' competency development over time was examined using the Mann-Whitney U test., Results: A total of 760 questionnaires meeting the inclusion criteria were analyzed. The overall Cronbach's alpha value was 0.964, and the item-total correlations were all greater than 0.520. The overall KMO measure was 0.966 and the KMO measure for each item was greater than 0.930 (P < 0.001). The eigenvalues of the top 3 components extracted were all greater than 1, explaining 55.351, 7.382, and 5.316% of data variance respectively, and 68.048% cumulatively. These components were aligned with the competency dimensions of skills (S), knowledge (K), and attitude (A). Significant and positive correlations (0.135 < Kendall's tau-b < 0.276, p < 0.05) were found between Year-4 students' self-rated competency levels and their scores for the licensing examination. Steady competency growth was associated with almost all indicators, with the most pronounced growth in the domain of skills. A lack of steady growth was seen in the indicators of "applying the English language" and "conducting scientific research & innovating"., Conclusions: The ASK-SEAT, a competency-based assessment scale developed to measure medical students' competency development shows good reliability and structural validity. For predictive validity, weak-to-moderate correlations are found between Year-4 students' self-assessment and their performance at the national licensing examination (Year-4 students start their clinical clerkship during the 2nd semester of their 4th year of study). Year-2 to Year-6 students demonstrate steady improvement in the great majority of clinical competency indicators, except in the indicators of "applying the English language" and "conducting scientific research & innovating"., (© 2022. The Author(s).)

D-β-hydroxybutyrate (D-3HB), a monomer of microbial polyhydroxybutyrate (PHB), is also a natural ketone body produced during carbohydrate deprivation to provide energy to the body cells, heart, and brain. In recent years, increasing evidence demonstrates that D-3HB can induce pleiotropic effects on the human body which are highly beneficial for improving physical and metabolic health. Conventional ketogenic diet (KD) or exogenous ketone salts (KS) and esters (KE) have been used to increase serum D-3HB level. However, strict adaptation to the KD was often associated with poor patient compliance, while the ingestion of KS caused gastrointestinal distresses due to excessive consumption of minerals. As for ingestion of KE, subsequent degradation is required before releasing D-3HB for absorption, making these methods somewhat inferior. This review provides novel insights into a biologically synthesized D-3HB (D-3-hydroxybutyric acid) which can induce a faster increase in plasma D-3HB compared to the use of KD, KS, or KE. It also emphasizes on the most recent applications of D-3HB in different fields, including its use in improving exercise performance and in treating metabolic or age-related diseases. Ketones may become a fourth micro-nutrient that is necessary to the human body along with carbohydrates, proteins, and fats. Indeed, D-3HB being a small molecule with multiple signaling pathways within the body exhibits paramount importance in mitigating metabolic and age-related diseases. Nevertheless, specific dose-response relationships and safety margins of using D-3HB remain to be elucidated with more research. KEY POINTS: • D-3HB induces pleiotropic effects on physical and metabolic health. • Exogenous ketone supplements are more effective than ketogenic diet. • d-3HB as a ketone supplement has long-term healthy impact., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Acute respiratory infections (ARI) cause considerable morbidity and mortality worldwide, especially in children. Unfortunately, there are limited multi-center data on common viral respiratory infections in south China., Methods: A total of 4403 nasal swabs were collected from children in 10 cities in Guangdong, China in 2019. Seven respiratory viruses, influenza A virus (IFA), influenza B virus (IFB), respiratory syncytial virus (RSV), adenoviruses (ADV) and parainfluenza virus types 1-3 (PIV1, PIV2 and PIV3), were detected by direct immunofluorescence antibody assay. The personal information and clinical characteristics were recorded and analyzed., Results: The results showed that at least one virus was detected in 1099 (24.96 %) samples. The detection rates of RSV, IFA, ADV, PIV3, PIV1 and PIV2 were 7.13 % (314/4403), 5.31 % (234/4403), 4.02 % (177/4403), 3.04 % (134/4403), 1.70 % (75/4403) and 1.16 % (51/4403), respectively. The detection rate of RSV was highest in 0-6-month-old children at 18.18 % (106/583), while the detection rate of IFA was highest in 12-18-year-old children at 20.48 % (17/83). The total detection rates in winter and spring were 35.67 % (219/614) and 34.56 % (403/1166), higher than those in summer, 17.41 % (284/1631), and autumn, 19.46 % (193/992)., Conclusions: RSV and IFA were the main respiratory viruses in children. With increasing age the detection rate of RSV decreased in children, but the trends for the detection rates of IFA and IFB were the opposite. This study provided the viral etiology and epidemiology of pediatric patients with ARI in Guangdong, China.

The economic viability of current bio-production systems is often limited by its low productivity due to slow cell growth and low substrate uptake rate. The fastest-growing bacterium Vibrio natriegens is a highly promising next-generation workhorse of the biotechnology industry which can utilize various industrially relevant carbon sources with high substrate uptake rates. Here, we demonstrate the first systematic engineering example of V. natriegens for the heterologous production of 1,3-propanediol (1,3-PDO) from glycerol. Systems metabolic engineering strategies have been applied in this study to develop a superior 1,3-PDO producer, including: (1) heterologous pathway construction and optimization; (2) engineering cellular transcriptional regulators and global transcriptomic analysis; (3) enhancing intracellular reducing power by cofactor engineering; (4) reducing the accumulation of toxic intermediate by pathway engineering; (5) systematic engineering of glycerol oxidation pathway to eliminate byproduct formation. A final engineered strain can efficiently produce 1,3-PDO with a titer of 56.2 g/L, a yield of 0.61 mol/mol, and an average productivity of 2.36 g/L/h. The strategies described in this study would be useful for engineering V. natriegens as a potential chassis for the production of other useful chemicals and biofuels., (Copyright © 2021 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Background: Extensile lateral approach had been recognized as the gold standard technique for displaced intra-articular calcaneus fractures (DIACFs) while sinus tarsi approach had been increasingly valued by surgeons and comparative clinical outcome was shown in both techniques. Appropriate decisions could be made by the clinicians with the help of cost-utility analysis (CUA) about optimal healthcare for type II/III calcaneus fracture., Method: A single-center, retrospective study was conducted in which basic characteristics, clinical outcomes, and health care costs of 109 patients had been obtained and analyzed. Changes in health-related quality of life (HRQoL) scores, validated by EuroQol five-dimensional-three levels (EQ-5D-3L), were used to enumerate quality-adjusted life years (QALYs). Cost-effectiveness was determined by the incremental cost per QALY., Results: One hundred nine patients were enrolled in our study including 62 in the ELA group and 47 in the STA group. There were no significant differences between these two groups in mean total cost, laboratory, and radiographic evaluation expense, surgery, anesthesia, and antibiotic expense. The expense of internal fixation materials ($3289.0 ± 543.9) versus ($2630.6 ± 763.7) and analgesia ($145.8 ± 85.6) versus ($102.9 ± 62.7) in ELA group were significantly higher than in the STA group (P < .001, P = .008, respectively). Visual Analogue Scale (VAS) scores showed significant difference at postoperative 3 and 5 days (P < .001). American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and the Bohlers' and Gissane angle showed no significant differences between the two groups before and after the operation. The cost-effectiveness ratios of ELA and STA were $8766.8 ± 2835.2/QALY and $7914.9 ± 1822.0/QALY respectively, and incremental cost-effectiveness ratio (ICERs) of ELA over STA was $32110.00/QALY, but both showed no significant difference., Conclusion: Both ELA and STA techniques are effective operative procedures for the patients with calcaneus fracture. Moreover, STA seems to be more reasonable for its merits including less postoperative pain, and less expense of analgesia as well as internal fixation materials., Level of Evidence: 5.

Indole, an important signal molecule in both intraspecies and interspecies, regulates a variety of bacterial behaviors, but its regulatory mechanism is still unknown. Pantoea agglomerans YS19, a preponderant endophytic bacterium isolated from rice, does not produce indole, yet it senses exogenous indole. In this study, a mutant of YS19-Rp r whose target gene expression was downregulated by indole was selected through mTn5 transposon mutagenesis. Using the TAIL-PCR technique, the mutation gene was identified as a cytR homologue, which encodes a cytidine repressor (CytR) protein, a bacterial transcription factor involved in a complex regulation scheme. The negative regulation of indole in cytR, which is equivalent to the mutation in cytR, promotes the expression of a downstream gene deoC, which encodes the key enzyme deoxyribose-phosphate aldolase in participating in pentose metabolism. We found that DeoC is one of the regulatory proteins of P. agglomerans that is involved in counteracting starvation. Furthermore, the expression of deoC was induced by starvation conditions, accompanied by a decrease in cytR expression. This finding suggests that the indole signal and the mutation of cytR relieve inhibition of CytR in the transcription of deoC, facilitating better adaptation of the bacterium to the adverse conditions of the environment., (Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Objective: To analyze the incidence and treatment of Clostridium difficile infection (CDI) in pediatric patients with antibiotic-associated diarrhea (AAD)., Method: Clinical data of totally 577 pediatric patients with AAD seen from January 2012 to January 2014 were collected; those children were divided according to age into 4 groups, 0.25 -1 year, >1 -4 years, >4 -12 years and >12 -18 years old groups, and 220 healthy children were enrolled as controls. CDI was tested by C. Diff Quik Chek Complete (QCC) and BD GeneOhm™ C. Diff Assay (BD-PCR) in all children, and the CDI incidence of four groups was added up. All pediatric patients with AAD were divided into mild, general and severe type according to different symptoms of diarrhea, and grading treatment, the general type and severe type of CDI children were treated with metronidazole and (or) vancomycin, afterwards, the results of grading treatment were analyzed., Result: The number of pediatric patients with AAD were 178, 177, 132 and 90 in 0. 25 - 1 year, > 1 -4 years, > 4 - 12 years and > 12 - 18 years old group, respectively. The positive rate of CDI (22. 0% (39/177)) in > 1 -4 years old AAD patients was very significantly higher compared to the controls (4% (4/91), P < 0. 001), the rate of CDI (21. 2% (28/132)) in > 4 - 12 years old AAD pediatric patients was significantly higher compared to the controls (4% (2/53), P = 0. 004), the rates of CDI in 0. 25 - 1 year and > 12 - 18years old AAD groups were not significantly different from that of the controls (P >0. 05). There were 285 mild type AAD children (no CDI children), 176 general type AAD children (including 47 CDI children), and 116 severe type AAD children (including 81 CDI children). After grading and symptomatic treatment, there were 16 recurrent diarrhea in 128 CDI patients (severe type AAD), and the rest recovered. Two cases were transferred for referral treatment, 2 cases died, and the rest 12 recurrent diarrhea children fully recovered after administration of metronidazole, vancomycin, probiotics and symptomatic treatment., Conclusion: The > 1 -12 years old AAD children had higher CDI rate than healthy children; administration of metronidazole and (or) vancomycin was effective for CD infection.