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Abstract The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial–immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial–immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.

Abstract A data‐driven Buck converter model identification method is proposed to deal with missing (incomplete) outputs, which is robust to the data length and percentage of missing data. A nuclear norm based convex optimization problem instead of linear interpolation, to guarantee the recovered missing data satisfying the potential model structured low‐rank character, is constructed to estimate missing outputs. The alternating direction method of multiplier strategy is used to solve the nuclear norm based convex optimization problem. In this way, the high‐quality missing data can be estimated, even for short data length and high percentage of missing data. Based on the recovered data, the subspace identification method provides accurate estimates of the structure and parameter of the Buck converter synchronously. By applying the proposed method to a Buck converter, experimental results demonstrate its effectiveness.

Abstract Background Human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined. Methods 57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR. Results This study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P

Abstract Objectives This study aimed to compare and evaluate different transverse width indices for diagnosing maxillary transverse deficiency (MTD), a common malocclusion characterized by uncoordinated dental arches, crossbites, and tooth crowding. Materials and methods Sixty patients aged 7–12 years were included in the study, with 20 patients diagnosed with MTD and 40 normal controls. Transverse width indices, including maxillary width at the buccal alveolar crest and lingual midroot level, as well as at the jugal process width, were measured. Differences between these indices and their corresponding mandibular indices were used as standardized transverse width indices. The reference range of these indices was determined and evaluated. Receiver operating characteristic (ROC) analysis was performed to evaluate their diagnostic ability. Results The transverse width indices and standardized transverse width indices of the MTD group were significantly smaller than those of the control group, except for the jugal process width. The evaluation of the reference range and ROC analysis revealed that the difference of the maxillomandibular width at buccal alveolar crest was the most accurate diagnostic method. Conclusions The jugal point analysis method may not be suitable for diagnosing MTD. Instead, measuring the difference in maxillomandibular width at the buccal alveolar crest proves to be a more reliable and accurate diagnostic method for MTD.

Abstract Unicystic ameloblastoma (UAM) of the jaw can be effectively reduced in volume through decompression, which promotes bone regeneration and restores jaw symmetry. This study quantitatively evaluated changes in mandible volume and symmetry following decompression of mandibular UAM. This study included 17 patients who underwent surgical decompression followed by second-stage curettage for mandibular UAM. Preoperative and postoperative three-dimensional computed tomography (CT) images were collected. Bone volume and the area of cortical perforation were measured to assess bone growth during decompression. Mandibular volumetric symmetry was analyzed by calculating the volumetric ratio of the two sides of the mandible. Twelve pairs of landmarks were identified on the surface of the lesion regions, and their coordinates were used to calculate the mean asymmetry index (AI) of the mandible. Paired t-tests and the Mann–Whitney U test were used for statistical analysis, with p

Objective: This study compared the reliabilities of three different methods used to calculate surgical deviations after mandibular reconstructions using free fibular flaps. Study design: This retrospective study involved 35 patients who underwent computer-assisted mandibular reconstructions using free fibula flaps. The deviations between the virtual surgical plans and the postoperative results were independently analyzed by two researchers using three distinct methods. In Method A, the fibular axis, the center of gravity, and the osteotomy plane served as landmarks when measuring surgical deviations. In Methods B and C, manually designated points were used to measure errors in the fibular length and intersegmental angle. The primary outcome variables were the intraclass correlation coefficients (ICCs) that revealed the inter-rater agreements for all three methods. Results: The use of Method A was associated with good agreement in terms of the fibular length deviation (ICC = 0.765) and intersegmental angle (ICC = 0.897); both were higher than those afforded by Methods B (ICC = 0.158 and 0.108) and C (ICC = 0.406 and 0.463). The measurements of the fibular transfer osteotomy deviation (ICC = 0.888), linear deviation (0.926), and angular deviation (0.958) were very reliable. Conclusions: Method A afforded the highest reliability in clinical practice when evaluating surgical deviations after mandibular reconstruction using fibular flaps.

Abstract Renal tubular epithelial cells (TECs) undergo an energy‐related metabolic shift from fatty acid oxidation to glycolysis during chronic kidney disease (CKD) progression. However, the mechanisms underlying this burst of glycolysis remain unclear. Herein, a new critical glycolysis regulator, the transcription factor forkhead box protein K1 (FOXK1) that is expressed in TECs during renal fibrosis and exhibits fibrogenic and metabolism‐rewiring capacities is reported. Genetic modification of the Foxk1 locus in TECs alters glycolytic metabolism and fibrotic lesions. A surge in the expression of a set of glycolysis‐related genes following FOXK1 protein activation contributes to the energy‐related metabolic shift. Nuclear‐translocated FOXK1 forms condensate through liquid‐liquid phase separation (LLPS) to drive the transcription of target genes. Core intrinsically disordered regions within FOXK1 protein are mapped and validated. A therapeutic strategy is explored by targeting the Foxk1 locus in a murine model of CKD by the renal subcapsular injection of a recombinant adeno‐associated virus 9 vector encoding Foxk1‐short hairpin RNA. In summary, the mechanism of a FOXK1‐mediated glycolytic burst in TECs, which involves the LLPS to enhance FOXK1 transcriptional activity is elucidated.

Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the intermediate and late stages of osseointegration, mesenchymal stem cells (MSCs) migrate and initiate their osteogenic functions, while macrophages support MSCs in osteogenesis. The utilization of ferroelectric P(VDF-TrFE) covered ITO planar microelectrodes facilitated the simulation of various surface charge to investigate their effects on MSCs’ osteogenic differentiation and macrophage polarization and the results indicated a parabolic increase in the promotional effect of both with the rise in piezoelectric coefficient. Furthermore, the surface charge with a piezoelectric coefficient of −18 exhibited the strongest influence on the promotion of M1 polarization of macrophages and the promotion of MSCs’ osteogenic differentiation. The impact of macrophage polarization and MSC osteogenesis following the interaction of macrophages affected by surface charge and MSC was ultimately investigated. It was observed that macrophages affected by the surface charge of −18 piezoelectric coefficient still exerted the most profound induced osteogenic effect, validating the essential role of M1-type macrophages in the osteogenic differentiation of MSCs.

PurposeThoracolumbar fascia injury is often associated with poor early pain relief after percutaneous vertebroplasty (PVP). This study will evaluate the effects of thoracolumbar fascia injury on early pain relief and time to get out of bed after PVP.MethodsA total of 132 patients treated with PVP for osteoporotic vertebral compression fractures (OVCF) were included and divided into injured group (52 cases) and non-injured group (80 cases) according to the existence of thoracolumbar fascia injury. Before surgery, 1 day, 3 days, 1 week, 1 month, and 3 months after surgery, and at the last follow-up, the primary patient-reported outcome measures (PROMs) were the visual analogue scale (VAS) of pain while rolling over and standing, and the secondary PROMs was the Oswestry disability index (ODI). Meanwhile, the achieved rate of minimal clinically important differences (MCID) and patient acceptable symptom states (PASS) of the above measures in both groups was evaluated at the last follow-up.ResultsExcept for the postoperative 3 months and the last follow-up, there were statistically significant differences in VAS-standing and ODI between the two groups at other time points after surgery (P 0.05). In addition, the proportion of patients who got out of bed 1 and 3 days after surgery in the non-injury group was significantly higher than that in the injury group (P = 0.000 for both).ConclusionThoracolumbar fascia injury significantly affected early pain relief and extended time of getting out of bed after PVP. Attention should be paid to preoperative evaluation of thoracolumbar fascial injury in order to better predict the postoperative efficacy of PVP.

Abstract Dental implants are widely used to replace missing teeth, providing patients with unparalleled levels of effectiveness, convenience, and affordability. The biological basis for the clinical success of dental implants is osseointegration. Bone aging is a high-risk factor for the reduced osseointegration and survival rates of dental implants. In aged individuals, mesenchymal stem cells (MSCs) in the bone marrow show imbalanced differentiation with a reduction in osteogenesis and an increase in adipogenesis. This leads to impaired osseointegration and implant failure. This review focuses on the molecular mechanisms underlying the dysfunctional differentiation of aged MSCs, which primarily include autophagy, transcription factors, extracellular vesicle secretion, signaling pathways, epigenetic modifications, microRNAs, and oxidative stress. Furthermore, this review addresses the pathological changes in MSCs that affect osseointegration and discusses potential therapeutic interventions to enhance osseointegration by manipulating the mechanisms underlying MSC aging.

Abstract. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by progressive lung fibrogenesis and histological features of usual interstitial pneumonia. IPF has a poor prognosis and presents a spectrum of disease courses ranging from slow evolving disease to rapid deterioration; thus, a differential diagnosis remains challenging. Several biomarkers have been identified to achieve a differential diagnosis; however, comprehensive reviews are lacking. This review summarizes over 100 biomarkers which can be divided into six categories according to their functions: differentially expressed biomarkers in the IPF compared to healthy controls; biomarkers distinguishing IPF from other types of interstitial lung disease; biomarkers differentiating acute exacerbation of IPF from stable disease; biomarkers predicting disease progression; biomarkers related to disease severity; and biomarkers related to treatment. Specimen used for the diagnosis of IPF included serum, bronchoalveolar lavage fluid, lung tissue, and sputum. IPF-specific biomarkers are of great clinical value for the differential diagnosis of IPF. Currently, the physiological measurements used to evaluate the occurrence of acute exacerbation, disease progression, and disease severity have limitations. Combining physiological measurements with biomarkers may increase the accuracy and sensitivity of diagnosis and disease evaluation of IPF. Most biomarkers described in this review are not routinely used in clinical practice. Future large-scale multicenter studies are required to design and validate suitable biomarker panels that have diagnostic utility for IPF.

In order to investigate the impact of different modeling methods of interface transition zone on the mechanical properties, damage and failure process of steel fiber reinforced concrete in numerical simulation, based on the unified phase-field theory and the cohesive zone model, two methods were used to establish a numerical calculation model of the interface transition zone of steel fiber reinforced concrete for the tensile test of concrete specimens containing a single steel fiber to compare and analyze the effects of different modeling methods on the mechanical properties and failure modes of steel fiber reinforced concrete, and the effects of different factors on the ultimate tensile strength of concrete containing a single steel fiber were investigated. The results show that the phase-field theory model for the matrix part and the cohesive zone model for the interface transition zone have good accuracy and reliability in both the calculation results and mesoscopic failure morphology; the tensile strength of steel fiber reinforced concrete with the initial crack location of 30 mm and 35 mm is 308% and 757% higher than that of 25 mm, respectively; the tensile strength of steel fiber reinforced concrete with the steel fiber embedding angle of 15°, 30°, and 45° is 122%, 308%, and 489% lower than that of 0°, respectively; the reinforcement effect of steel fiber is greatly influenced by the initial crack location and the embedding angle of steel fiber, and is relatively less influenced by the diameter of steel fiber. Adopting the unified phase-field theory can lower the analysis difficulty while guarantee higher computational accuracy, which provides theoretical reference for the study of the damage and fracture process of steel fiber reinforced concrete.

Background: With the acceleration of the aging process of the population, the number of edentulous patients continuously increased. Edentulism induces the loss of occlusal relationship and cause adverse effects on the stomatognathic system. Temporomandibular joint (TMJ), as a significant component of this system, may also be affected by edentulism in the process of supporting mandibular movement. Purpose: Provide a comprehensive review of the structure and function of TMJ in the edentulous population, as well as the prevalence of temporomandibular joint disorder (TMD) in edentulous group. Study selection: An electronic search was conducted on articles prior to December 2022 to filter all papers relevant to the structure and function of TMJ in edentulous population. The internet databases (PubMed, Cochrane Library, Embase) were searched using various combinations of keywords for “edentulism” or “edentulous” and “TMJ” or “TMD”. Results: Firstly, 522 articles were selected from the internet database, and finally, a total of 44 articles met the inclusion and exclusion criteria. The research content of these articles mainly focuses on the structure and function of TMJ in edentulous patients, as well as the clinical signs and symptoms of TMD. Conclusions: Edentulous arch induces the loss of occlusal relationship, which may lead to degenerative changes of TMJ components consisting of changes in morphology and bone mass density of condyle, articular fossa, and articular eminence. In addition, the condyle could be shifted backward and upward, and displacement of the articular disc may occur after dentition loss. And the condyle and the articular disc may be guided back to the normal position after effective prosthodontic treatment. But the conclusions of the study on the function of TMJ and the prevalence of TMD in edentulous people are inconsistent. The condition of TMJ, especially the position of condyle-fossa and the symptoms and signs of TMD should not be ignored. If necessary, radiographic examinations should be performed.

With the development of modern medicine, the research methods of occurrence, development and treatment of orthopedic diseases are developing rapidly. The microenvironment provided by traditional orthopedic research methods differ considerably from the human body, resulting in poor or inconsistent conclusions in previous studies. Microfluidic technology has shown its advantages in the field of orthopedic research, especially in providing bionic mechanical stimulation environment. The microfluidic device can simulate the complex internal environment through the fine and complex structure and perfusion control system, and provide a stable, controllable and efficient culture system. Moreover, it can serve as a manufacturing device, which can produce bone grafts or bone like organs for tissue engineering with bionic structure. It can also simultaneously act as a detection device, which can realize high-throughput detection of small samples at low cost. In addition, we can establish in vitro physiological or pathological models on microfluidic systems to assist in the diagnosis and treatment of orthopedic diseases. This paper reviews the medical application of microfluidic devices in orthopedics.

Motor Imagery (MI) based on Electroencephalography (EEG), a typical Brain-Computer Interface (BCI) paradigm, can communicate with external devices according to the brain’s intentions. Convolutional Neural Networks (CNN) are gradually used for EEG classification tasks and have achieved satisfactory performance. However, most CNN-based methods employ a single convolution mode and a convolution kernel size, which cannot extract multi-scale advanced temporal and spatial features efficiently. What’s more, they hinder the further improvement of the classification accuracy of MI-EEG signals. This paper proposes a novel Multi-Scale Hybrid Convolutional Neural Network (MSHCNN) for MI-EEG signal decoding to improve classification performance. The two-dimensional convolution is used to extract temporal and spatial features of EEG signals and the one-dimensional convolution is used to extract advanced temporal features of EEG signals. In addition, a channel coding method is proposed to improve the expression capacity of the spatiotemporal characteristics of EEG signals. We evaluate the performance of the proposed method on the dataset collected in the laboratory and BCI competition IV 2b, 2a, and the average accuracy is at 96.87%, 85.25%, and 84.86%, respectively. Compared with other advanced methods, our proposed method achieves higher classification accuracy. Then we use the proposed method for an online experiment and design an intelligent artificial limb control system. The proposed method effectively extracts EEG signals’ advanced temporal and spatial features. Additionally, we design an online recognition system, which contributes to the further development of the BCI system.

Abstract Objectives Pulmonary lesion is frequently seen in ANCA-associated vasculitis (AAV) patients primarily due to AAV lung involvement or infection, which are hard to differentiate due to their high similarity in clinical manifestations. We aimed to analyze the clinical features of pulmonary lesions consequent to AAV involvement or infection in AAV patients and further identify the markers for differential diagnosis. Methods 140 AAV patients who admitted to the Renmin Hospital of Wuhan University from January 2016 to July 2021 were included in this study. According to the nature of lung conditions, these patients were divided into the non-pulmonary lesion group, the lung infection group and the non-pulmonary infection group, and their demographics, clinical symptoms, imaging features, as well as laboratory findings were compared. A receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of single biomarker and composite biomarkers on pulmonary infection was then evaluated. Results The patients in the lung infection group were significantly older than those in the no lesion group (63.19 ± 14.55 vs 54.82 ± 15.08, p = 0.022). Patients in the lung infection group presented more frequent symptoms and more obvious pulmonary image findings. Compared with patients in the non-pulmonary infection group, patients in the lung infection group showed a higher symptom incidence of fever, chest tightness, cough and expectoration, and hemoptysis (52.94% vs 16.00%, 61.76% vs 40.00%, 72.06% vs 46.00%, 27.94% vs 8.00%, p

Fat deposition is an economically important trait in pigs. Ningxiang pig, one of the four famous indigenous breeds in China, is characterized by high fat content. The underlying gene expression pattern in different developmental periods of backfat tissue remains unclear, and the purpose of this investigation is to explore the potential molecular regulators of backfat tissue development in Ningxiang pigs. Backfat tissue (three samples for each stage) was initially collected from different developmental stages (60, 120, 180, 240, 300, and 360 days after birth), and histological analysis and RNA sequencing (RNA-seq) were then conducted. Fragments per kilobase of transcript per million (FPKM) method was used to qualify gene expressions, and differentially expressed genes (DEGs) were identified. Furthermore, strongly co-expressed genes in modules, which were named by color, were clustered by Weighted gene co-expression network analysis (WGCNA) based on dynamic tree cutting algorithm. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment were subsequently implemented, and hub genes were described in each module. Finally, QPCR analysis was employed to validate RNA-seq data. The results showed that adipocyte area increased and adipocyte number decreased with development of backfat tissue. A total of 1,024 DEGs were identified in five comparison groups (120 days vs. 60 days, 180 days vs. 120 days, 240 days vs. 180 days, 300 days vs. 240 days, and 360 days vs. 300 days). The turquoise, red, pink, paleturquoise, darkorange, and darkgreen module had the highest correlation coefficient with 60, 120, 180, 240, 300, and 360 days developmental stage, while the tan, black and turquoise module had strong relationship with backfat thickness, adipocyte area, and adipocyte number, respectively. Thirteen hub genes (ACSL1, ACOX1, FN1, DCN, CHST13, COL1A1, COL1A2, COL6A3, COL5A1, COL14A1, OAZ3, DNM1, and SELP) were recognized. ACSL1 and ACOX1 might perform function in the early developmental stage of backfat tissue (60 days), and FN1, DCN, COL1A1, COL1A2, COL5A1, COL6A3, and COL14A1 have unignorable position in backfat tissue around 120 days developmental stage. Besides, hub genes SELP and DNM1 in modules significantly associated with backfat thickness and adipocyte area might be involved in the process of backfat tissue development. These findings contribute to understand the integrated mechanism underlying backfat tissue development and promote the progress of genetic improvement in Ningxiang pigs.

Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury (PNI), not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell (SC) cords migration and axons elongation. Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects, systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce. This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration, and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them, encompassing (1) in vitro prevascularization, (2) in vivo prevascularization, and (3) stimulation of neurovascularization in situ. Furthermore, we emphasize that the lack of accuracy for structure and spatiotemporal regulation, as well as the operational inconvenience and delayed connection to the host’s nerve stumps, have stuck the existing neurovascularization technology in the preclinical stage. The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.

Optical vortices in a topological defect of cosmic space-time.

Introduction: The decoding of the motor imaging electroencephalogram (MI-EEG) is the most critical part of the brain-computer interface (BCI) system. However, the inherent complexity of EEG signals makes it challenging to analyze and model them.Methods: In order to effectively extract and classify the features of EEG signals, a classification algorithm of motor imagery EEG signals based on dynamic pruning equal-variant group convolutional network is proposed. Group convolutional networks can learn powerful representations based on symmetric patterns, but they lack clear methods to learn meaningful relationships between them. The dynamic pruning equivariant group convolution proposed in this paper is used to enhance meaningful symmetric combinations and suppress unreasonable and misleading symmetric combinations. At the same time, a new dynamic pruning method is proposed to dynamically evaluate the importance of parameters, which can restore the pruned connections.Results and Discussion: The experimental results show that the pruning group equivariant convolution network is superior to the traditional benchmark method in the benchmark motor imagery EEG data set. This research can also be transferred to other research areas.

The nature of the Mesolithic in China has not been studied much due to the few well-context sites discovered and excavated during this period. The situation also restricts the understanding of human subsistence in the Mesolithic period in China, especially in the arid region. The present paper reports the flotation results at Locality 10 of the Pigeon Mountain site in Northwest China. Ten species of plants belonging to six families were identified, dominated by Agriophyllum squarrosum and Artemisia sieversiana. No firm evidence proves the domestication. Combined with the lithic artefacts in QG10, ancient people could utilize plant resources by constructing or expanding the food spectrum. It is the first systematic archaeobotany work in the Paleolithic site of Northwest China. The result reminds us that the enhanced utilization of wild plant resources is a vital subsistence for Mesolithic people in arid regions.

Summary: Renal tubular epithelial cells (TECs) undergoing partial epithelial-mesenchymal transition (pEMT) during renal fibrosis has been recognized as a featuring and detrimental event. However, the mechanism for redirecting the cell fate of pEMT remains unclear. Here we mapped the temporal expression trajectories of a series of EMT-related molecules in renal fibrosis. It revealed a unique expression profile of N-cadherin of initial rising and late dropdown, which is distinct from that of other mesenchymal markers. The transcription factor Foxk1, which serves as a negative regulator of the N-cadherin gene, was induced by TGF-β1 but was tightly regulated in the presence of JNK-associated leucine zipper protein (JLP). The loss of JLP resulted in Foxk1 induction, leading to N-cadherin downregulation and compromised cell viability. We propose a novel axis consisting of JLP/Foxk1/N-cadherin in shaping the EMT program and suggest JLP as the checkpoint of the EMT continuum during renal fibrosis progression.

Abstract Mandibular defects caused by injuries, tumors, and infections are common and can severely affect mandibular function and the patient’s appearance. However, mandible reconstruction with a mandibular bionic structure remains challenging. Inspired by the process of intramembranous ossification in mandibular development, a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced. Moreover, the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible. The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function. According to the results of in vivo experiments, the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics. The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone, indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development. Thus, hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction. Moreover, the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.

In this paper, the sieve bootstrap test for multiple change points in the mean of long memory sequence is studied. Firstly, the ANOVA test statistics for change points detection is obtained. Secondly, sieve bootstrap statistics is constructed and the consistency under the Mallows measure is proved. Finally, the effectiveness of the method was illustrated by simulation and example analysis. Simulation results show that our method can not only control the empirical size well but also have reasonable good power.

Background: Peritoneal dialysis-related peritoneal fibrosis is the leading cause of peritoneal ultrafiltration failure. Multitude factors and pathological processes have been implicated in peritoneal fibrosis development and progression, whereas the intrinsic anti-fibrotic mechanism has rarely been explored. JNK-associated leucine zipper protein (JLP) has been recently found possessing powerful anti-fibrotic merits of overall antagonizing TGF-β-induced profibrotic effects. Objectives: We wondered whether JLP is expressed in the peritoneum, and if so, whether it exerts the anti-fibrotic effects similar to those in the kidney. Method: Here, we examined and confirmed JLP expression in peritoneum tissue of mice. Then, we established a peritoneal fibrosis model in Jlp wild-type and Jlp global deficient mice and observed the different effects of Jlp on peritoneal fibrosis progression. In vitro studies were performed on peritoneal mesothelial HMrSV5 cells with or without Jlp knockdown to investigate the underlying mechanism by which Jlp exerts anti-fibrotic effects. Results: We found that the expression of JLP decreased in a high-glucose peritoneal dialysis solution (HGPDS)-induced peritoneal fibrosis mouse model and in HGPDS-treated peritoneal mesothelial cell HMrSV5. JLP deletion exacerbated HGPDS-induced peritoneal fibrosis in peritoneal fibrosis mice, and knockdown of JLP resulted in an increased profibrotic response to HGPDS stimulation in HMrSV5 cells, which was associated with epithelial-to-mesenchymal transition, elevated autophagy, and apoptosis, as well as enhanced TGF-β1/Smad signaling activation. Conclusions: Our findings revealed a new anti-fibrotic factor of Jlp involved in peritoneal fibrosis induction and shed light on novel therapeutic targets in peritoneal ultrafiltration failure.

BackgroundOsteoblastoma is quite rare in the oromaxillo-facial region, while the mandible is always the predilection. However, in our case, the lesion was located in the left temporal articular tubercle, involving the adjacent skull base, which is extremely rare in the literature.Case reportsIt had been diagnosed as the most common temporomandibular joint disorder in the local hospital before the patient came to our department, mainly due to the primary symptom, that was, the patient got pain in the left temporomandibular joint area while opening the mouth. However, we found a mass of bone lesions at the left temporal articular tubercle in MRI and cone beam CT, and it turned out to be an osteoblastoma after surgery. The patient's primary symptom disappeared after recovering from the surgery, and there have been no indications of complication or recurrence up to now.ConclusionOsteoblastoma is very rare in the temporomandibular joint region. It could easily miss the possibility of a benign tumor due to its unusual location and confusing chief complaint in this case. Our report provides experience in the identification of osteoblastoma in rare sites.

Abstract Background The association between low birth weight (LBW) and dental caries is currently unclear. The aim of this study was to investigate the association of LBW with dental caries in permanent teeth in children of Ningbo city. Methods A total of 1975 children aged 11-to-13 years in Ningbo, China were enrolled in this cross-sectional study. LBW was defined as a birthweight

Background: Dog bite wounds usually have severe local soft tissue damage and the wounds are likely to be contaminated by a large number of bacteria or even a series of rare pathogenic bacteria, leading to repeated infection and delayed wound healing. Recombinant human basic fibroblast growth factor (rh-bFGF) has excellent ability to promote wound repair and widely used in various complicated wounds. Objective: Observe the clinical efficacy of Recombinant human basic Fibroblast growth factor (rh-bFGF) applicated in the treatment of dog bite wounds. Methods: A total of 31 patients (16 adult and 15 aged) with rabies exposure grade Ⅲ dog bite wounds treated in the department of emergency surgery in our hospital from February 2020 to February 2022 were reviewed. Rh-bFGF was applied in the wounds after debridement and the patients were treated with preventive anti-inflammatory therapy. Observe the wound healing rules, infection rate, related complications and application time of antibiotics. Results: Eventually, all the wound were well healed and the healing time needed for most patients were about 2–3 weeks. The wound infection rate of aged patients was much higher, therefore application time of intravenous antibiotics injection in the aged patients was significantly higher than it in the adults (P < 0.05), but the difference of the time reach the intermittent wound dressing change was not statistically significant (P > 0.05). Conclusion: Rh-bFGF is safe and reliable for severe dog bite wounds in both the elderly and adults, it may help improve the early stage healing speed of aged patients, but the specific treatment needs to be individualized and accurate depends on different personal physique and wound conditions.

Biomedical image registration refers to aligning corresponding anatomical structures among different images, which is critical to many tasks, such as brain atlas building, tumor growth monitoring, and image fusion-based medical diagnosis. However, high-throughput biomedical image registration remains challenging due to inherent variations in the intensity, texture, and anatomy resulting from different imaging modalities, different sample preparation methods, or different developmental stages of the imaged subject. Recently, Generative Adversarial Networks (GAN) have attracted increasing interest in both mono- and cross-modal biomedical image registrations due to their special ability to eliminate the modal variance and their adversarial training strategy. This paper provides a comprehensive survey of the GAN-based mono- and cross-modal biomedical image registration methods. According to the different implementation strategies, we organize the GAN-based mono- and cross-modal biomedical image registration methods into four categories: modality translation, symmetric learning, adversarial strategies, and joint training. The key concepts, the main contributions, and the advantages and disadvantages of the different strategies are summarized and discussed. Finally, we analyze the statistics of all the cited works from different points of view and reveal future trends for GAN-based biomedical image registration studies.

Ophiostomatoid fungi exhibit a complex relationship with bark beetles; exhausting of host tree defenses is traditionally regarded as one of the key benefits provided to beetle vectors. Ophiostoma bicolor is one of the dominant species of the mycobiota associated with Ips genus bark beetles which infect the spruce trees across the Eurasian continent. Host spruce trees resist fungal invasion through structural and inducible defenses, but the underlying mechanisms at the molecular level, particularly with respect to the interaction between bark beetle-associated fungi and host trees, remain unclear. The aim of this study was to observe the pathological physiology and molecular changes in Picea koraiensis seedlings after artificial inoculation with O. bicolor strains (TS, BH, QH, MX, and LWQ). This study showed that O. bicolor was a weakly virulent pathogen of spruce, and that the virulent of the five O. bicolor strains showed differentiation. All O. bicolor strains could induce monoterpenoid release. A positive correlation between fungal virulence and release of monoterpenoids was observed. Furthermore, the release rate of monoterpenoids peaked at 4 days post-inoculation (dpi) and then decreased from 4 to 90 dpi. Transcriptomic analysis at 4 dpi showed that many plant-pathogen interaction processes and mitogen-activated protein kinase (MAPK) metabolic processes were activated. The expression of monoterpenoid precursor synthesis genes and diterpenoid synthesis genes was upregulated, indicating that gene expression regulated the release rate of monoterpenoids at 4 dpi. The enriched pathways may reveal the immune response mechanism of spruce to ophiostomatoid fungi. The dominant O. bicolor possibly induces the host defense rather than defense depletion, which is likely the pattern conducted by the pioneers of beetle-associated mycobiota, such as Endoconidiophora spp.. Overall, these results facilitate a better understanding of the interaction mechanism between the dominant association of beetles and the host at the molecular level.

Autophagy is an immune homeostasis process induced by multiple intracellular and extracellular signals. Inflammation is a protective response to harmful stimuli such as pathogen microbial infection and body tissue damage. Porphyromonas gingivalis infection elicits both autophagy and inflammation, and dysregulation of autophagy and inflammation promotes pathology. This review focuses on the interaction between autophagy and inflammation caused by Porphyromonas gingivalis infection, aiming to elaborate on the possible mechanism involved in the interaction.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to acute kidney injury. The authors describe that SARS-COV-2 can directly infect human kidney, possibly mediating tubular pathogenesis.

Background This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. Methods In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. Results In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14–1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p

Introduction Acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients is associated with poor prognosis. Early prediction and intervention of AKI are vital for improving clinical outcome of COVID-19 patients. As lack of tools for early AKI detection in COVID-19 patients, this study aimed to validate the USCD-Mayo risk score in predicting hospital-acquired AKI in an extended multi-center COVID-19 cohort. Methods Five hundred seventy-two COVID-19 patients from Wuhan Tongji Hospital Guanggu Branch, Wuhan Leishenshan Hospital, and Wuhan No. Ninth Hospital was enrolled for this study. Patients who developed AKI or reached an outcome of recovery or death during the study period were included. Predictors were evaluated according to data extracted from medical records. Results Of all patients, a total of 44 (8%) developed AKI. The UCSD-Mayo risk score achieved excellent discrimination in predicting AKI with the C-statistic of 0.88 (95%CI: 0.84–0.91). Next, we determined the UCSD-Mayo risk score had good overall performance (Nagelkerke R2 = 0.32) and calibration in our cohort. Further analysis showed that the UCSD-Mayo risk score performed well in subgroups defined by gender, age, and several chronic comorbidities. However, the discrimination of the UCSD-Mayo risk score in ICU patients and patients with mechanical ventilation was not good which might be resulted from different risk factors of these patients. Conclusions We validated the performance of UCSD-Mayo risk score in predicting hospital-acquired AKI in COVID-19 patients was excellent except for patients from ICU or patients with mechanical ventilation.

Abstract Mechanical cues are widely used for regulating cell behavior because of their overarching, extensive, and non‐invasive advantages. However, unlike chemical cues, mechanical cues are not efficient enough to determine cell fate independently and improving the mechanosensitivity of cells is rather challenging. In this study, the combined effect of chemical and mechanical cues on the osteogenic differentiation of human mesenchymal stem cells is examined. These results show that chemical cues such as the presence of an osteogenic medium, induce cells to secrete more collagen, and induce integrin for recruiting focal adhesion proteins that mature and cascade a series of events with the help of the mechanical force of the scaffold material. High‐resolution, highly ordered hollow‐micro‐frustum‐arrays using double‐layer lithography, combined with modified methacrylate gelatin loaded with pre‐defined soluble chemicals to provide both chemical and mechanical cues to cells. This approach ultimately facilitates the achievement of cellular osteodifferentiation and enhances bone repair efficiency in a model of femoral fracture in vivo in mice. Moreover, the results also reveal these pivotal roles of Integrin α2/Focal adhesion kinase/Ras homolog gene family member A/Large Tumor Suppressor 1/Yes‐associated protein in human mesenchymal stem cells osteogenic differentiation both in vitro and in vivo. Overall, these results show that chemical cues enhance the microtopographical sensitivity of cells.

Abstract Background The SARS-CoV-2 RNA was detected positive again after discharged from hospital in some COVID-19 patients, with or without clinical symptoms such as fever or dry cough. Methods 1008 severe COVID-19 patients, with SARS-CoV-2 RNA positive detected with the mixed specimen of nasopharyngeal swab and oropharyngeal swab by real-time fluorescence quantitative PCR (RT-qPCR), were selected to monitor SARS-CoV-2 RNA with the 12 types of specimens by RT-qPCR during hospitalization. All of 20 discharged cases with COVID-19 were selected to detect SARS-CoV-2 RNA in isolation period with 7 types of specimens by RT-qPCR before releasing the isolation period. Results Of the enrolled 1008 severe patients, the nasopharyngeal swab specimens showed the highest positive rate of SARS-CoV-2 RNA (71.06%), followed by alveolar lavage fluid (66.67%), oropharyngeal swab (30.77%), sputum (28.53%), urine (16.30%), blood (12.5%), stool (12.21%), anal swab (11.22%) and corneal secretion (2.99%), and SARS-CoV-2 RNA couldn’t be detected in other types of specimen in this study. Of the 20 discharged cases during the isolation period, the positive rate of SARS-CoV-2 RNA was 30% (6/20): 2 cases were positive in sputum at the eighth and ninth day after discharge, respectively, 1 case was positive in nasopharynx swab at the sixth day after discharge, 1 case was positive in anal swab at the eighth day after discharge, and 1 case was positive in 3 specimens (nasopharynx swab, oropharynx swab and sputum) simultaneously at the fourth day after discharge, and no positive SARS-CoV-2 RNA was detected in other specimens including stool, urine and blood at the discharged patients. Conclusions SARS-CoV-2 RNA should be detected in multiple specimens, such as nasopharynx swab, oropharynx swab, sputum, and if necessary, stool and anal swab specimens should be performed simultaneously at discharge when the patients were considered for clinical cure and before releasing the isolation period.

Three-dimensional (3D) hydrogel printing enables production of volumetric architectures but achieving good resolutions for miniaturized features remains challenging. Here the authors demonstrate shrinking of a printed structure by immersing a 3D-printed patterned hydrogel consisting of a hydrophilic polyionic polymer network in a solution of polyions of the opposite net charge.

This work presents a robust finite-time output feedback control method for a number of nonlinear systems that suffer unpredictable time-varying disturbances. The developed method takes advantage of control techniques based on a finite-time state observer used to estimate the lumped disturbance, where the estimator plays an important role in online compensation after being transmitted to a corresponding controller. Besides, with the state estimation provided by the finite-time state observer, the finite-time output feedback controller can guarantee the finite-time stability of the closed-loop system. The experimental results validate the effectiveness of the developed method on the trajectory tracking control of a robot manipulator.

Summary: Carbon materials have attracted extensive attention in the past decades due to the rich configurations and outstanding properties. Numerous efforts have been dedicated to obtaining two-dimensional (2D) materials inheriting the properties of graphene. Herein, from first-principles calculations, we report a novel 2D carbon allotrope with a hybridized sp2-sp3 network, i.e., “grapheneplus (graphene+)”. Both the Dirac properties of graphene and the negative Poisson’s ratio (NPR) of penta-graphene are inherited in graphene+. The NPR behavior manifests itself along the out-of-plane direction only when it is stretched, namely, out-of-plane half-auxeticity, which is different from the already known NPR behavior. Besides, the Dirac nodes form a nodal loop that remains robust regardless of the application of uniaxial/biaxial strain and electric field. In addition, graphene+ is found to be energetically more stable than penta-graphene, which promises a potentially easier synthesis. In short, graphene+ could act as a strong competitor to graphene.

ObjectiveAnti-epidemic work against coronavirus disease (COVID) has become routine work in China. Our study was intended to investigate the emotional and psychological state of healthcare workers and look for the association between sociodemographic factors/profession-related condition and emotional state.MethodsA cross-sectional survey was conducted online among healthcare workers from various backgrounds. Symptoms of anxiety and depression were assessed by the Chinese versions of the seven-item Generalized Anxiety Disorder (GAD-7) and the nine-item Patient Health Questionnaire (PHQ-9), respectively. Supplementary questions (Supplementary Material) were recorded to describe the participants’ information about workplace violence, profession, and attitude related to the COVID pandemic. Wherever suitable, independent t-test, and one-way ANOVA were performed to detect group differences of GAD-7 and PHQ-9 total scores after grouping by sociodemographic variables, respectively, such as age, gender, marital status, educational level, after-tax income, department category, job title, experience of workplace violence, and anti-epidemic participation. Multiple linear regression analyses (stepwise method) were utilized in order to look for the potential associated factors of GAD-7 and PHQ-9 total scores.ResultsA total of 2,139 questionnaires with valid response were completed. Approximately 86.44% of participants had minimal symptoms of anxiety, 11.08% mild, 1.59% moderate, and 0.89% severe. Meanwhile, 81.34% had minimal symptoms of depression, 14.07% mild, 2.90% moderate, 1.17% moderately severe, and 0.51% severe. Student’s t-test showed that participants with female gender, with experience of workplace violence scored higher on both GAD-7 and PHQ-9, and participants with experience of anti-epidemic front-line work during pandemic scored lower on both GAD-7 and PHQ-9. ANOVA showed that participants aging from 31 to 40, with higher educational level, with middle level of annual after-tax income, with department of internal medicine or surgery, or with middle level of job title scored higher on both GAD-7 and PHQ-9. Regression analyses showed that female gender, high job title, and the experience of workplace violence positively were associated with anxiety or depression. Doctoral education, department (other vs. psychiatry), job enthusiasm, and professional self-identity were negatively associated with anxiety or depression. Additionally, psychological support was negatively associated with depression.ConclusionAs the epidemic prevention and control against COVID-19 become normalized in China, emotional state of healthcare workers deserves extensive attention. Our study revealed that gender, educational level, department category, job title, the experience of workplace violence, job enthusiasm, and professional self-identity are the most important influencing factors of physician’s anxiety and depression. Self-tailored psychological intervention should be based on the predisposing factors above to mentally prepare healthcare workers for this long-lasting battle against COVID-19.

Contrasting with the predominance of blade-based assemblages in the Eurasian Upper Paleolithic, the large-scale persistence of a core-and-flake technology remains one of the defining features of Late Pleistocene lithic technology in East Asia. In North China, Shuidonggou is an exceptional site where both technologies are documented, therefore, it is an important archaeological sequence to understand regional technological evolution during the Marine Isotopic Stage 3. Blade technology first occurred at Shuidonggou Locality 1 and 2 around 41 ka cal BP while core-and-flake assemblages were widespread in North China. However, systematic technological studies on assemblages postdating 34 ka cal BP have not been conducted to examine whether the blade technology appeared and disappeared over a short yet abrupt episode, or persists and integrates into other forms in the region. Here, we conducted qualitative and quantitative analyses to reconstruct lithic productions on the assemblages at Shuidonggou Locality 2, dated after 34 ka cal BP. Our results show that there is a total absence of laminar elements in stone artifacts dated to 34–28 ka cal BP at Shuidonggou. Instead, we observe a dominance of an expedient production of flakes in the younger assemblages, illustrating a rapid return to flake-based technology after a relatively brief episode of stone blade production. Combining archaeological, environmental, and genetic evidence, we suggest that this technological ‘reversal’ from blades back to core and flake technology reflect population dynamics and adaptive strategies at an ecological interface between East Asian winter and summer monsoon.

Interface has a significant effect on mechanical properties of graphene reinforced metal composites. Taking graphene nanosheet reinforced iron composite (Gr/Fe) as an example, the interfacial characteristics of Gr/Fe (110), (111), (112¯), and (001) interfaces have been studied using molecular dynamics (MD) simulations. Two types of interfacial bonding have been examined: physical and chemical bonding. The results show that when the graphene and iron form a physical adsorption (weak-bonded) interface, the interactive energy of the graphene and Fe (110), (111), (112¯), and (001) interface is −1.00 J/m2, −0.73 J/m2, −0.82 J/m2, and −0.81 J/m2, respectively. The lengths of the Fe-C bonding are distributed in the range of 2.20–3.00 Å without carbide formation, and no distinct patterns of atomic structure are identified. When the graphene and iron form a chemical (strong-bonded) interface, the corresponding interactive energy is −5.63 J/m2, −4.32 J/m2, −4.39 J/m2, and −4.52 J/m2, respectively. The lengths of the Fe-C bonding are mainly distributed in the ranges of 1.80–2.00 Å and 2.30–2.50 Å, which the carbides such as Fe3C and Fe7C3 are formed at the interface. Moiré patterns are observed at different-oriented interfaces, because of the lattice geometrical mismatch between graphene and different-oriented iron crystal structures. The pattern of diamond stripe is at the (110) interface, which is in good accordance with the experiment. Other patterns are the hexagonal pattern at the (111) interface, the wavy stripe pattern at the (112¯) interface, and the chain pattern at the (001) interface. These moiré patterns are formed through the competition and coordination of the three binding sites (Hollow, Bridge, and Top) of graphene with Fe atoms.

Carcinoma of the mandibular gingiva is common and can more easily invade the mandibular bone compared with other head and neck cancers. Tumours that approach or involve the mandible usually require marginal resection or segmental resection of the mandible. Marginal mandibulectomy was not associated with worse prognosis than segmental mandibulectomy. However, these two conventional surgical methods lead to significant disability including loss of hard and soft tissues, impaired function of speech, swallowing and mastication. Rehabilitation can be difficult or impossible due to the distorted postsurgical anatomy. There are rare clinical studies on the surgical method for the mandibular gingival carcinoma in situ. In this study we introduce a modified surgical method, buccal partial mandibulectomy, focusing on how to keep the alveolar bone crest and lingual gingiva of the lesion in the largest extent for patients with mandibular gingival carcinoma in situ. Being more appropriate than traditional marginal or segmental mandibulectomy, the modified surgical method can not only ablate the whole tumour with negative margin in soft tissue, but also achieve higher quality of postoperative life without tumour recurrence during the longest followup time of more than 40 months. Buccal partial mandibulectomy can maintain the jaw continuity and make it possible to achieve an adequate prosthetic rehabilitation such as implant-fixed prothesis. [ABSTRACT FROM AUTHOR]

Abstract Natural extracellular matrices (ECMs) are three-dimensional (3D) and multi-scale hierarchical structure. However, coatings used as ECM-mimicking structures for osteogenesis are typically two-dimensional or single-scaled. Here, we design a distinct quasi-three-dimensional hierarchical topography integrated of density-controlled titania nanodots and nanorods. We find cellular pseudopods preferred to anchor deeply across the distinct 3D topography, dependently of the relative density of nanorods, which promote the osteogenic differentiation of osteoblast but not the viability of fibroblast. The in vivo experimental results further indicate that the new bone formation, the relative bone-implant contact as well as the push-put strength, are significantly enhanced on the 3D hierarchical topography. We also show that the exposures of HFN7.1 and mAb1937 critical functional motifs of fibronectin for cellular anchorage are up-regulated on the 3D hierarchical topography, which might synergistically promote the osteogenesis. Our findings suggest the multi-dimensions and multi-scales as vital characteristic of cell-ECM interactions and as an important design parameter for bone implant coatings.

A comprehensive performance analysis of artificial noise (AN) assisted secure transmission in multiple-input single-output (MISO) wiretap channels was presented.It was shown that the AN scheme did not always improve the security,and provided an exact signal-to-noise ratio (SNR) threshold below which AN did not work.An explicit result of the optimal power allocation (OPA) using the lower bound to the ergodic secrecy rate (ESR) was presented and the OPA for the worst case without the knowledge of the eavesdropper’s relative distance was also provided.Simulations demonstrate that the proposed power allocation result achieves a higher ESR than the equal one.

Objective: The purpose of this study was to explore the clinical applications of high-throughput sequencing (HTS) in the identification of pathogens in patients with urinary tract infection (UTI), peritoneal dialysis-associated peritonitis (PDAP), central venous catheter related blood infections (CRBIs), and lung infections in the nephrology department. Methods: Midstream urine samples from 112 patients with UTI, peritoneal fluid samples from 67 patients with PDAP, blood samples from 15 patients with CRBI, and sputum specimens from 53 patients with lung infection were collected. The HTS and ordinary culture methods were carried out in parallel to identify the pathogens in each sample. Pathogen detection positive rate and efficacy were compared between the two methods. Results: The pathogen positive detection rates of HTS in UTI, PDAP, CRBI, and lung infection were strikingly higher than those of the culture method (84.8% vs. 35.7, 71.6% vs. 23.9%, 75% vs. 46.7%, 84.9% vs. 5.7%, p < 0.05, respectively). HTS was superior to the culture method in the sensitivity of detecting bacteria, fungi, atypical pathogens, and mixed microorganisms in those infections. In patients who had empirically used antibiotics before the test being conducted, HTS still exhibited a considerably higher positive rate than the culture method (81.6% vs. 39.0%, 68.1% vs. 14.9%, 72.7% vs. 36.4%, 83.3% vs. 4.2%, p < 0.05, respectively). Conclusions: HTS is remarkably more efficient than the culture method in detecting pathogens in diverse infectious diseases in nephrology, and is particularly potential in identifying the pathogens that are unable to be identified by the common culture method, such as in cases of complex infection with specific pathogens or subclinical infection due to preemptive use of antibiotics.

A 3D cell culture has developed rapidly in recent years, as cells growing on a flat substrate in a static environment are far from achieving an in vivo status. Currently, researchers have also gradually realized that to achieve cell morphology, structure, and physiological functions in vitro, 3D cell culture should be capable of simulating key features of an in vivo environment, including the interaction of cell–cell, cell–extracellular matrix (ECM), and cell–organ interactions. Herein, the development of the 3D cell culture system related to the following three perspectives is outlined: 1) biomaterial systems with a hydrogel system as the core; 2) biomanufacturing technology with bioprinting as the main means; and 3) culture device systems supported by microfluidic chips and bioreactors. The question is whether 3D cell culture will be as popular as 2D culture in the future. The key may lie in the development of simple and standard protocols for 3D culture.

While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases. In situ hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of Il6, Il8 and Il1b genes in infected primary macrophages and DCs in vitro, and SARS-CoV-2-NP+ macrophages and DCs also manifested high levels of IL-6 and IL-1β, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia in vivo. Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.

Dental caries is one of the most common infectious diseases affecting 6-8-year-old children, especially their first permanent molars (FPMs). This study explored the prevalence of dental caries on FPMs by analyzing the oral health status of 1,423,720 children aged 6-8 years in Zhejiang Province, China. The data were extracted from the dental electronic records of the schoolchildren attending the Oral Health Promotion Project (OHPP), conducted during 2013-2017 in Zhejiang Province. Multiple logistic regression models were used to determine the factors affecting dental caries. Boys and girls accounted for 53.2% and 46.8% of the subjects, respectively. From 2013 to 2017, the prevalence of dental caries on FPMs increased: 2013: 20.4%; 2014: 25.3%; 2015: 24.5%; 2016: 27.0%; and 2017: 29.0%, despite the OHPP conducted. Based on multiple logistic regression model, girls had a significantly higher risk of FPM caries compared to boys (OR = 1.38, 95% CI: 1.37-1.39, p < 0.0001); compared with the caries rates in urban areas, the caries risk was significantly higher in rural areas (OR = 1.15, 95% CI: 1.14-1.16, p < 0.0001). In terms of geographic location in Zhejiang Province, the odds ratios of the caries risk of the east, south, west, and north were 1.35 (1.33-1.36), 1.3 (1.28-1.31), 0.81 (0.8-0.83), and 0.82 (0.81-0.84), respectively (p < 0.0001), by considering the central region as a reference. The caries prevalence of FPMs was high, with an increasing tendency and gender, social, cultural, and environmental factors affecting the caries prevalence.