Search

Osteoradionecrosis (ORN) is described as a disease with exposed, nonviable bone that fails to heal spontaneously or by means of conservative treatment after radiotherapy in at least 3 months. Though traditional theories in the early stage including hypoxic-hypocellular-hypovascular and fibro-atrophic in addition to new findings such as ferroptosis were put forward to explain the mechanisms of the osteoradionecrosis, the etiology of ORN is still unclear. With the high rate of occurrence in the head and neck area, especially in the mandible, this disease can disrupt the shape and function of the irradiated area, leading to a clinical presentation ranging from stable small areas of asymptomatic exposed bone to severe progressive necrosis. In severe cases, patients may experience pain, xerostomia, dysphagia, facial fistulas, and even a jaw defect. Consequently, sequence therapy and sometimes extensive surgery and reconstructions are needed to manage these sequelae. Treatment options may include pain medication, antibiotics, the removal of sequesters, hyperbaric oxygen therapy, segmental resection of the mandible, and free flap reconstruction. Microanastomosed free-flaps are considered to be promising choice for ORN reconstruction in recent researches, and new methods including three-dimensional (3-D) printing, pentoxifylline, and amifostine are used nowadays in trying increase the success rates and improve quality of the reconstruction. This review summarizes the main research progress in osteoradionecrosis and reconstruction treatment of osteoradionecrosis with mandibular defect.

The anti-depressant effect of berberine (BBR) has been widely reported. However, the underlying mechanism remains unclear. The microbiota-gut-brain (MGB) axis plays a key role in the pathogenesis of depression. Therefore, we aimed to explore the anti-depressant mechanisms of BBR involving the association of the gut microbiota, neurotransmitters, BDNF, and SCFAs in chronic unpredictable mild stress (CUMS)-induced depressive rats.The antidepressant effects of BBR were detected by open-field test, 1 % sucrose preference test and body weight test in CUMS-induced depressive rats. 16S rDNA sequencing was performed to identify the change of gut microbiota. The concentrations of fecal SCFAs were analyzed by GC-MS targeted metabolomics. At the same time, neurotransmitters and BDNF expression were measured by enzyme linked immunosorbent assay (ELISA).BBR improved depression-like behaviors in CUMS rats by increasing the expression of serotonin (5-HT), norepinephrine (NE), dopamine (DA), and BDNF in the hippocampus. BBR regulates Firmicutes, Bacteroidetes, and Lachnospiraceae in depressive rats, resulting in the alteration of the synthesis and metabolism of SCFAs, including acetic, propanoic, and isovaleric acids.Direct evidence that BBR improves depressive behaviors via gut microbiota-SCFAs-brain axis is lacking, and only male rats were investigated in the present study.The anti-depressant mechanism of BBR is related to the regulation of the MGB axis via modulating the gut microbiota-SCFAs-monoamine neurotransmitters/BDNF.

Autism spectrum disorders caused by both genetic and environmental factors are strongly male-biased neuropsychiatric conditions. However, the mechanism underlying the sex bias of autism spectrum disorders remains elusive. Here, we use a mouse model in which the autism-linked gene Cttnbp2 is mutated to explore the potential mechanism underlying the autism sex bias. Autism-like features of Cttnbp2 mutant mice were assessed via behavioural assays. C-FOS staining identified sex-biased brain regions critical to social interaction, with their roles and connectivity then validated by chemogenetic manipulation. Proteomic and bioinformatic analyses established sex-biased molecular deficits at synapses, prompting our hypothesis that male-biased nutrient demand magnifies Cttnbp2 deficiency. Accordingly, intakes of branched-chain amino acids (BCAA) and zinc were experimentally altered to assess their effect on autism-like behaviours. Both deletion and autism-linked mutation of Cttnbp2 result in male-biased social deficits. Seven brain regions, including the infralimbic area of the medial prefrontal cortex (ILA), exhibit reduced neural activity in male mutant mice but not in females upon social stimulation. ILA activation by chemogenetic manipulation is sufficient to activate four of those brain regions susceptible to Cttnbp2 deficiency and consequently to ameliorate social deficits in male mice, implying an ILA-regulated neural circuit is critical to male-biased social deficits. Proteomics analysis reveals male-specific downregulated proteins (including SHANK2 and PSD-95, two synaptic zinc-binding proteins) and female-specific upregulated proteins (including RRAGC) linked to neuropsychiatric disorders, which are likely relevant to male-biased deficits and a female protective effect observed in Cttnbp2 mutant mice. Notably, RRAGC is an upstream regulator of mTOR that senses BCAA, suggesting that mTOR exerts a beneficial effect on females. Indeed, increased BCAA intake activates the mTOR pathway and rescues neuronal responses and social behaviours of male Cttnbp2 mutant mice. Moreover, mutant males exhibit greatly increased zinc demand to display normal social behaviours. Mice carrying an autism-linked Cttnbp2 mutation exhibit male-biased social deficits linked to specific brain regions, differential synaptic proteomes and higher demand for BCAA and zinc. We postulate that lower demand for zinc and BCAA are relevant to the female protective effect. Our study reveals a mechanism underlying sex-biased social defects and also suggests a potential therapeutic approach for autism spectrum disorders.

Congenital CMV (cCMV) infection causes neurological sequelae in newborns. Recent studies of cCMV pathogenesis in animal models reveal ventriculomegaly and cortical atrophy associated with impaired neural progenitor cell (NPC) proliferation and migration.

Background Outdoor air pollution has been found to trigger systemic inflammatory responses and aggravate the activity of certain rheumatic diseases. However, few studies have explored the influence of air pollution on the activity of ankylosing spondylitis (AS). As patients with active AS in Taiwan can be reimbursed through the National Health Insurance programme for biological therapy, we investigated the association between air pollutants and the initiation of reimbursed biologics for active AS. Methods Since 2011, hourly concentrations of ambient air pollutants, including PM2.5, PM10, NO2, CO, SO2, and O3, have been estimated in Taiwan. Using Taiwanese National Health Insurance Research Database, we identified patients with newly diagnosed AS from 2003 to 2013. We selected 584 patients initiating biologics from 2012 to 2013 and 2336 gender-, age at biologic initiation-, year of AS diagnosis- and disease duration-matched controls. We examined the associations of biologics initiation with air pollutants exposure within 1 year prior to biologic use whilst adjusting for potential confounders, including disease duration, urbanisation level, monthly income, Charlson comorbidity index (CCI), uveitis, psoriasis and the use of medications for AS. Results are shown as adjusted odds ratio (aOR) with 95% confidence intervals (CIs). Results The initiation of biologics was associated with exposure to CO (per 1 ppm) (aOR, 8.57; 95% CI, 2.02–36.32) and NO2 (per 10 ppb) (aOR, 0.23; 95% CI, 0.11–0.50). Other independent predictors included disease duration (incremental year, aOR, 8.95), CCI (aOR, 1.31), psoriasis (aOR, 25.19), use of non-steroidal anti-inflammatory drugs (aOR, 23.66), methotrexate use (aOR, 4.50; 95% CI, 2.93–7.00), sulfasalazine use (aOR, 12.16; 95% CI, 8.98–15.45) and prednisolone equivalent dosages (mg/day, aOR, 1.12). Conclusions This nationwide, population-based study revealed the initiation of reimbursed biologics was positively associated with CO levels, but negatively associated with NO2 levels. Major limitations included lack of information on individual smoking status and multicollinearity amongst air pollutants.

Artificial molecular machines have captured the imagination of researchers, given their clear potential to mimic and influence human life. Key to behavior simulation is to reproduce the specific properties of physical or abstract systems. Dice throwing, as a stochastic model, is commonly used for result judgment or plan decision in real life. In this perspective we utilize DNA cube framework for the design of a dice device at the nanoscale to reproduce probabilistic events in different situations: equal probability, high probability, and low probability. We first discuss the randomness of DNA cube, or dice, adsorbing on graphene oxide, or table, and then explore a series of events that change the probability through the way in which the energy released from entropy-driven strand displacement reactions or changes in intermolecular forces. As such, the DNA nano-dice system provides guideline and possibilities for the design, engineering, and quantification of behavioral probability simulation, a currently emerging area of molecular simulation research.

BackgroundProteus mirabilis is one of the pathogens commonly causing urinary tract infections (UTIs). The molybdate-binding protein ModA encoded by modA binds molybdate with high affinity and transports it. Increasing evidence shows that ModA promotes the survival of bacteria in anaerobic environments and participates in bacterial virulence by obtaining molybdenum. However, the role of ModA in the pathogenesis of P. mirabilis remains unknown.ResultsIn this study, a series of phenotypic assays and transcriptomic analyses were used to study the role of ModA in the UTIs induced by P. mirabilis. Our data showed that ModA absorbed molybdate with high affinity and incorporated it into molybdopterin, thus affecting the anaerobic growth of P. mirabilis. Loss of ModA enhanced bacterial swarming and swimming and up-regulated the expression of multiple genes in flagellar assembly pathway. The loss of ModA also resulted in decreased biofilm formation under anaerobic growth conditions. The modA mutant significantly inhibited bacterial adhesion and invasion to urinary tract epithelial cells and down-regulated the expression of multiple genes associated with pilus assembly. Those alterations were not due to anaerobic growth defects. In addition, the decreased bacteria in the bladder tissue, the weakened inflammatory damage, the low level of IL-6, and minor weight change was observed in the UTI mouse model infected with modA mutant.ConclusionHere, we reported that in P. mirabilis, ModA mediated the transport of molybdate, thereby affecting the activity of nitrate reductase and thus affecting the growth of bacteria under anaerobic conditions. Overall, this study clarified the indirect role of ModA in the anaerobic growth, motility, biofilm formation, and pathogenicity of P. mirabilis and its possible pathway, and emphasized the importance of the molybdate-binding protein ModA to P. mirabilis in mediating molybdate uptake, allowing the bacterium to adapt to complex environmental conditions and cause UTIs. Our results provided valuable information on the pathogenesis of ModA-induced P. mirabilis UTIs and may facilitate the development of new treatment strategies.

Wild animals may encounter multiple challenges especially food shortage and altered diet composition in their suboptimal ranges. Yet, how the gut microbiome responds to dietary changes remains poorly understood. Prior studies on wild animal microbiomes have typically leaned upon relatively coarse dietary records and individually unresolved fecal samples. Here, we conducted a longitudinal study integrating 514 time-series individually recognized fecal samples with parallel fine-grained dietary data from two Skywalker hoolock gibbon (Hoolock tianxing) groups populating high-altitude mountainous forests in western Yunnan Province, China. 16S rRNA gene amplicon sequencing showed a remarkable seasonal fluctuation in the gibbons’ gut microbial community structure both across individuals and between the social groups, especially driven by the relative abundances of Lanchnospiraceae and Oscillospiraceae associated with fluctuating consumption of leaf. Metagenomic functional profiling revealed that diverse metabolisms associated with cellulose degradation and short-chain fatty acids (SCFAs) production were enriched in the high-leaf periods possibly to compensate for energy intake. Genome-resolved metagenomics further enabled the resolving metabolic capacities associated with carbohydrate breakdown among community members which exhibited a high degree of functional redundancy. Our results highlight a taxonomically and functionally sensitive gut microbiome actively responding to the seasonally shifting diet, facilitating the survival and reproduction of the endangered gibbon species in their suboptimal habitats.

Acute myeloid leukemia (AML) is a fast-growing and highly fatal blood cancer, and recent research has shown that targeting metabolism may be a promising therapeutic approach for treating AML. One promising target is the human mitochondrial NAD(P)+-dependent malic enzyme (ME2), which is involved in the production of pyruvate and NAD(P)H and the regulation of the NAD+/NADH redox balance. Inhibition of ME2 via silencing ME2 or utilizing its allosteric inhibitor disodium embonate (Na2EA) causes a decrease in pyruvate and NADH, leading to a decrease in producing ATP via cellular respiration and oxidative phosphorylation. ME2 inhibition also decreases NADPH levels, resulting in an increase in reactive oxygen species (ROS) and oxidative stress, which ultimately leads to cellular apoptosis. Additionally, ME2 inhibition reduces pyruvate metabolism and the biosynthetic pathway. ME2 silencing inhibits the growth of xenotransplanted human AML cells, and the allosteric ME2 inhibitor Na2EA demonstrates antileukemic activity against immune-deficient mice with disseminated AML. Both of these effects are a result of impaired energy metabolism in mitochondria. These findings suggest that the targeting ME2 may be an effective strategy for treating AML. Overall, ME2 plays an essential role in energy metabolism of AML cells, and its inhibition may offer a promising approach for AML treatment.

Context Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4+ T cells in the early stage of kidney tubular injury remains unknown. Objective To evaluate the role of PDHA1 in the regulation of tubular cells and CD4+ T cells and further to study its interaction in tubular cell injury in T1DM. Methods Plasma and total RNA were collected from T cells of T1DM patients (n = 35) and healthy donors (n = 33) and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, PDHA1, and biomarkers of CD4+ T cells including T helper 1 cells (Th1) and regulatory T cells (Treg) markers. HK-2 cells cocultured with CD4+ T cells from T1DM patients or healthy donors (HDs) to evaluate the interaction with CD4+ T cells. Results Increased PDHA1 gene expression levels in CD4+ T cells were positively associated with the plasma level of NGAL in T1DM patients and HDs. Our data demonstrated that the Th1/Treg subsets skewed Th1 in T1DM. Knockdown of PDHA1 in kidney tubular cells decreased ATP/ROS production, NAD/NADH ratio, mitochondrial respiration, and cell apoptosis. Furthermore, PDHA1 depletion induced impaired autophagic flux. Coculture of tubular cells and T1DM T cells showed impaired CPT1A, upregulated FASN, and induced kidney injury. Conclusion Our findings indicate that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, thereby indicating a new therapeutic approach for kidney tubular injury in T1DM.

Probing the adlayer structures on an electrode/electrolyte interface is one of the most important tasks in modern electrochemistry for clarifying the electrochemical processes. Herein, we have combined cyclic voltammetry and electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy techniques to explore the potential-dependent adlayer structures on Au(111) in a room-temperature ionic liquid of 1-butyl-3-methylimidazolium hexafluorophosphate (BMIPF

Three-dimensional (3D) porous boron-doped diamond (BDD) film is an attractive electrode material but tough to synthesize. Herein, the 3D porous BDD films were constructed in a facile and template-free way. The BDD/non-diamond carbon (NDC) composite films were firstly fabricated by hot filament chemical vapor deposition (HFCVD) technique, and then the porous BDD films with 3D interconnected porous microstructure, different pore size and NDC-free diamond were achieved by selective removal of NDC. It is manifested that higher electrochemical response, large double layer capacitance (17.54 mF/cm2) in diamond electrodes, wide electrochemical window of 2.6 V and superior long-term stability were achieved for 3D porous BDD film. This derives from the synergistic effect of microstructure and phase composition of the porous films. 3D interconnected structure possesses prominent improvement of effective surface area and accessible porous channel, significantly enhancing the species adsorption and mass transfer. The 3D porous BDD films, composed of NDC-free diamond, exhibit excellent structural stability and corrosion resistance, which favor the enhancement of long-term stability and water splitting overpotential. The facile fabricating approach and excellent structure/electrochemical character demonstrate the appealing application in many electrochemical fields for 3D porous BDD films, such as energy storage and conversion, wastewater treatment and purification.

Background: Artemisia argyi Lévl. et Van., Artemisia princeps Pamp., and Artemisia montana Pamp., which are the sources of mugwort, have been popular across East Asian countries for nearly 2000 years now. Essential oils are the major chemical component obtained from them, exhibiting a variety of biological activities. Objective: This review mainly focuses on the chemical composition and biological activities of A. argyi essential oil (AAEO), A. princeps essential oil (APEO), and A. montana essential oil (AMEO), with a special focus on their common and specific characteristics. The traditional use, distribution, and botany of A. argyi, A. princeps, and A. montana have also been summarized. In addition, the pharmacokinetics of AAEO was involved. Methods: We collected literature from online and offline databases by entering the following keywords: mugwort, wormwood, A. argyi, A. princeps, A. montana, essential oil, and volatile oil. No language limitation was present in our search. Results: A. argyi, A. princeps, and A. montana were used as traditional medicine, food, and health care products for a long time in Asia. They are widely distributed in most parts of China, Korea, and Japan. AAEO, APEO, and AMEO were all composed of monoterpenes, sesquiterpenes and their derivatives, alkanes olefins, etc. Most of the specific compounds of AAEO were monoterpenoids, nearly half of the specific compounds of APEO were aliphatic hydrocarbons, and the sesquiterpenes were the typical specific compounds of AMEO. The mugwort essential oil showed multiple biological activities, such as anti-microbial, anti-inflammatory, antioxidant, antitumor, anticoagulation, sedative, and insecticide. Conclusion: The present review provided insight into the chemical composition and biological activity of AAEO, APEO, and AMEO. The comprehensive literature showed that they possessed wide application prospects in various fields. However, they should be studied in more depth. The underlying bioactive mechanisms should be elucidated and their toxicity and quality control should be determined.

Background: Outdoor air pollution has been found to trigger systemic inflammatory responses and aggravate the activity of certain rheumatic diseases. However, few studies have explored the influence of air pollution on the activity of ankylosing spondylitis (AS). As patients with active AS in Taiwan can be reimbursed through the National Health Insurance program for biological therapy, we investigated the association between air pollutants and the initiation of biologics for active disease in patients with AS. Methods: Since 2011, hourly concentrations of ambient air pollutants, including PM2.5, PM10, NO2, CO, SO2 and O3 have been estimated in Taiwan. Using Taiwanese National Health Insurance Research Database, we identified patients with newly diagnosed AS from 2003 to 2013. We selected 584 patients initiating biologics from 2012 to 2013 and 2,336 gender-, age at biologic initiation-, year of AS diagnosis- and disease duration-matched controls. We examined the associations of biologics initiation with air pollutants exposure within one year prior to biologic use while adjusting for potential confounders, including disease duration, urbanisation level, monthly income, Charlson comorbidity index (CCI), uveitis, psoriasis, inflammatory bowel disease and the use of medications for AS. Results are shown as adjusted odds ratio (aOR) with 95% confidence intervals (CIs). Results: The initiation of biologics was associated with exposure to CO (per 1 ppm) (aOR, 8.58; 95% CI, 2.02–36.35), and NO2 (per 10 ppb) (aOR, 0.23; 95% CI, 0.11–0.50). Other independent predictors included disease duration (incremental year, aOR, 8.97), CCI (aOR, 1.31), psoriasis (aOR, 25.06), use of non-steroidal anti-inflammatory drugs (aOR, 23.66), methotrexate use (aOR, 4.53; 95% CI, 2.93–7.00), sulfasalazine use (aOR, 12.15; 95% CI, 8.98–15.45) and prednisolone equivalent dosages (mg/day, aOR, 1.11). Conclusions: This nationwide, population-based study revealed that the initiation of biologics was positively associated with CO levels, but negatively associated with NO2 levels.

Blood contact materials require strong anti-fouling capabilities to avoid thrombus formation. Recently, TiO2-based photocatalytic antithrombotic treatment has gained focus. Nevertheless, this method is restricted to titanium materials with photocatalytic abilities. This study offers an alternative solution that can be applied to a broader range of materials: piranha solution treatment. Our findings revealed that the free radicals generated by the treatment effectively altered the surface physicochemical properties of various inorganic materials, enhancing their surface hydrophilicity and oxidizing organic contaminants, thus improving their antithrombotic properties. Additionally, the treatment resulted in contrasting effects on the cellular affinity of SS and TiO2. While it significantly reduced the adhesion and proliferation of SMCs on SS surfaces, it significantly enhanced these on TiO2 surfaces. These observations suggested that the impact of the piranha solution treatment on the cellular affinity of biomaterials was closely tied to the intrinsic properties of the materials. Thus, materials suitable for piranha solution treatment could be selected based on the functional requirements of implantable medical devices. In conclusion, the broad applicability of piranha solution surface modification technology in both blood-contact and bone implant materials highlights its promising prospects.

BackgroundHyperuricemia and gout are risk factors of nephrolithiasis. However, it is unclear whether the ABCG2 gene contributes to the development of nephrolithiasis. We aimed to investigate the interaction between the ABCG2 rs2231142 variant and incident nephrolithiasis in the Taiwanese population.MethodsA total of 120,267 adults aged 30–70 years were enrolled from the Taiwan Biobank data-base in this retrospective case–control study and genotyped for rs2231142. The primary outcome was the prevalence of self-reported nephrolithiasis. The odds ratio (OR) of incident nephrolithiasis was analyzed by multivariable logistic regression models with adjustment for multifactorial confounding factors. Associations of the ABCG2 rs2231142 variant with serum uric acid levels, and the incident nephrolithiasis were explored.ResultsThe frequency of rs2231142 T allele was 53%, and 8,410 participants had nephrolithiasis. The multivariable-adjusted OR (95% confidence interval) of nephrolithiasis was 1.18 (1.09–1.28) and 1.12 (1.06–1.18) for TT and GT genotypes, respectively, compared with the GG genotype (pConclusionsABCG2 genetic variation is a significant risk of nephrolithiasis, independent of serum uric acid levels. For rs2231142 T allele carriers, our result provides evidence for precision healthcare to tackle hyperuricemia, comorbidities, smoking, and overweight, and recommend regular physical exercise for the prevention of nephrolithiasis.

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p p = 0.073), especially among patients whose with an inactive disease activity was p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.

Pig producers have suffered serious economic losses from porcine epidemic diarrhea virus (PEDV) infection. Development of PEDV antibodies for detection or treatment has become an important research direction.The S1/S2 junction (S1S2J) cleavage site of S protein of PEDV is one of the major determinants of coronavirus infection success. In this study, we specifically selected the S1S2J protein of PEDV-AJ1102 (a representative strain of the G2 type) as target protein to immunise mice and generated monoclonal antibodies (mAbs) using hybridoma technology. Three mAbs showed high-binding activity to the S1S2J protein were further analysed. To reveal the characterisation of mAbs, variable region genes of antibodies were studied by using DNA sequencing, which revealed differences in their CDR3 amino acid sequences. We then developed a new method to identify the isotypes of these three mAbs. Results showed that these three antibodies were of the IgM type. As for the functions of these three mAbs, indirect immunofluorescence assay confirmed their good binding ability to Vero E6 cells infected with PEDV-SP-C strain (G1 type). Epitope analysis showed linear epitopes for all three mAbs. These antibodies were also used to detect infected cells via flow cytometry analysis. In summary, we have prepared and examined three mAbs against PEDV-S1S2J. The focal antibodies can be employed as detection antibodies for diagnostic reagents and further developed for other applications. We also designed a novel technique for easy and cost-saving identification of isotypes of mouse mAbs. Our results lay a good foundation for the development of research for PEDV.

We report multifunctional tendon-mimetic hydrogels constructed from anisotropic assembly of aramid nanofiber composites. The stiff nanofibers and soft polyvinyl alcohol in these anisotropic composite hydrogels (ACHs) mimic the structural interplay between aligned collagen fibers and proteoglycans in tendons. The ACHs exhibit a high modulus of ~1.1 GPa, strength of ~72 MPa, fracture toughness of 7333 J/m 2 , and many additional characteristics matching those of natural tendons, which was not achieved with previous synthetic hydrogels. The surfaces of ACHs were functionalized with bioactive molecules to present biophysical cues for the modulation of morphology, phenotypes, and other behaviors of attached cells. Moreover, soft bioelectronic components can be integrated on ACHs, enabling in situ sensing of various physiological parameters. The outstanding mechanics and functionality of these tendon mimetics suggest their further applications in advanced tissue engineering, implantable prosthetics, human-machine interactions, and other technologies.

BackgroundThe high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient.MethodsWe retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months.ResultsThe HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1–2, 20.3% based on SPSP 1–3, and 20.8% based on SPSPII 1–3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months.ConclusionThe HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis.Trial registrationClinicalTrial.gov, identifier: NCT04516577.

Patients with castration-resistant prostate cancer (CRPC) often develop drug resistance after treatment with enzalutamide. The goal of our study was to identify the key genes related to enzalutamide resistance in CRPC and to provide new gene targets for future research on improving the efficacy of enzalutamide. Differential expression genes (DEGs) associated with enzalutamide were obtained from the GSE151083 and GSE150807 datasets. We used R software, the DAVID database, protein–protein interaction networks, the Cytoscape program, and Gene Set Cancer Analysis for data analysis. The effect of RAD51 knockdown on prostate cancer (PCa) cell lines was demonstrated using Cell Counting Kit-8, clone formation, and transwell migration experiments. Six hub genes with prognostic values were screened (RAD51, BLM, DTL, RFC2, APOE, and EXO1), which were significantly associated with immune cell infiltration in PCa. High RAD51, BLM, EXO1, and RFC2 expression was associated with androgen receptor signaling pathway activation. Except for APOE, high expression of hub genes showed a significant negative correlation with the IC50 of Navitoclax and NPK76-II-72-1. RAD51 knockdown inhibited the proliferation and migration of PC3 and DU145 cell lines and promoted apoptosis. Additionally, 22Rv1 cell proliferation was more significantly inhibited with RAD51 knockdown than without RAD51 knockdown under enzalutamide treatment. Overall, six key genes associated with enzalutamide resistance were screened (RAD51, BLM, DTL, RFC2, APOE, and EXO1), which are potential therapeutic targets for enzalutamide-resistant PCa in the future.

Incorporating two-dimensional (2D) diamond nanosheets with fluorescent color centers exhibits great potential in the application of quantum sensing. However, color centers always show poor optical emission in chemical-vapor-deposited (CVD) diamond nanomaterials. To address this issue, Si doped diamond/graphite hybrid films were successfully fabricated in microwave-plasma CVD device. The films consist of diamond-core/graphite-shell nanosheets with high amount of diamond nanocrystalline particles. Two post treatments of acid oxidation and annealing in air were used to tailor photoluminescence (PL) of silicon-vacancy (SiV) centers. The SiV centers in the oxidized samples exhibit small PL increase compared with the as-deposited samples with SiV PL quenching. It is found that the graphite phase is selectively etched away with the presence of nanocrystalline diamond particles during the treatment of acid oxidation while the nanocrystalline diamond particles are efficiently removed with the presence of graphite using the air annealing method. Based on this result, a two-step approach of acid oxidation followed by air annealing was conducted to etch the non-diamond phase, forming diamond nanosheets. The SiV centers exhibit significant PL enhancement with a maximum value of 28 folds, compared with the single-step oxidized samples. The Raman and XPS results reveal that such PL increase originates from direct bonding of oxygen on the sp3 carbon. Therefore, our work provides a feasible approach to prepare 2D diamond nanosheets with high-brightness color centers.