Recent Advances in Dopamine-Based Membrane Surface Modification and Its Membrane Distillation Applications.

Surface modification of membranes is essential for improving flux and resistance to contamination for membranes. This is of great significance for membrane distillation, which relies on the vapor pressure difference across the membrane as the driving force. In recent years, biomimetic mussel-inspired substances have become the research hotspots. Among them, dopamine serves as surface modifiers that would achieve highly desirable and effective membrane applications owing to their unique physicochemical properties, such as universal adhesion, enhanced hydrophilicity, tunable reducibility, and excellent thermal conductivity. The incorporation of a hydrophilic layer, along with the utilization of photothermal properties and post-functionalization capabilities in modified membranes, effectively addresses challenges such as low flux, contamination susceptibility, and temperature polarization during membrane distillation. However, to the best of our knowledge, there is still a lack of comprehensive and in-depth discussions. Therefore, this paper systematically compiles the modification method of dopamine on the membrane surface and summarizes its application and mechanism in membrane distillation for the first time. It is believed that this paper would provide a reference for dopamine-assisted membrane separation during production, and further promote its practical application.

Small extracellular vesicles derived from lipopolysaccharide-preconditioned dental follicle cells inhibit cell apoptosis and alveolar bone loss in periodontitis.

OBJECTIVE: This study aimed to explore the effects of small extracellular vesicles derived from lipopolysaccharide-preconditioned dental follicle cells (L-D-sEV) on periodontal ligament cells from periodontitis affected teeth (p-PDLCs) in vitro and experimental periodontitis in mice. DESIGN: In vitro, the biological function of p-PDLCs and the underlying molecular mechanism were investigated by flow cytometry, Western blot, and quantitative real-time PCR (qRT-PCR) analysis. Eighteen-eight-week-old male C57BL/6 mice were randomly divided into three groups: control (Con), periodontitis (Peri), and L-D-sEV groups. Mice periodontitis model was induced by placing the 5-0 silk thread (around the maxillary second molar) and P.gingivalis (1 ×107 CFUs per mouse). In vivo, the alveolar bone loss, osteoclast activity, and macrophage polarization were measured by micro-computed tomography and histological analysis. RESULTS: In vitro, the RANKL/OPG ratio and phosphorylation of JNK and P38 protein levels of p-PDLCs were significantly decreased after L-D-sEV administration. Besides, flow cytometry and qRT-PCR analysis showed that L-D-sEV reduced apoptosis of p-PDLCs, down-regulated apoptosis-related genes Caspase-3 and BCL-2-Associated X expression, and up-regulated B-cell lymphoma-2 gene levels. In vivo, L-D-sEV administration significantly reduced alveolar bone loss, inhibited osteoclast activity, and induced M2 polarization. The histological analysis showed that iNOS/CD206, RANKL/OPG, p-JNK/JNK, and p-P38/P38 ratios were significantly lower in the L-D-sEV group than in the Peri group. CONCLUSIONS: L-D-sEV administration alleviated alveolar bone loss by mediating RANKL/OPG-related osteoclast activity and M2 macrophage polarization, alleviating p-PDLCs apoptosis and proliferation via the JNK and P38 pathways.

Developing deep LSTMs with later temporal attention for predicting COVID-19 severity, clinical outcome, and antibody level by screening serological indicators over time.

OBJECTIVE: The clinical course of COVID-19, as well as the immunological reaction, is notable for its extreme variability. Identifying the main associated factors might help understand the disease progression and physiological status of COVID-19 patients. The dynamic changes of the antibody against Spike protein are crucial for understanding the immune response. This work explores a temporal attention (TA) mechanism of deep learning to predict COVID-19 disease severity, clinical outcomes, and Spike antibody levels by screening serological indicators over time. METHODS: We use feature selection techniques to filter feature subsets that are highly correlated with the target. The specific deep Long Short-Term Memory (LSTM) models are employed to capture the dynamic changes of disease severity, clinical outcome, and Spike antibody level. We also propose deep LSTMs with a TA mechanism to emphasize the later blood test records because later records often attract more attention from doctors. RESULTS: Risk factors highly correlated with COVID-19 are revealed. LSTM achieves the highest classification accuracy for disease severity prediction. Temporal Attention Long Short-Term Memory (TA-LSTM) achieves the best performance for clinical outcome prediction. For Spike antibody level prediction, LSTM achieves the best permanence. CONCLUSION: The experimental results demonstrate the effectiveness of the proposed models. The proposed models can provide a computer-aided medical diagnostics system by simply using time series of serological indicators.

Hydroxyapatite-Coated Small Intestinal Submucosa Membranes Enhanced Periodontal Tissue Regeneration through Immunomodulation and Osteogenesis via BMP-2/Smad Signaling Pathway.

Periodontitis, a chronic infection causing periodontal tissue loss, may be effectively addressed with in situ tissue engineering. Small intestinal submucosa (SIS) offers exceptional biocompatibility and biodegradability but lacks sufficient osteoconductive and osteoinductive properties. This study develops and characterizes SIS coated with hydroxyapatite (SIS-HA) and gelatin methacrylate hydroxyapatite (SIS-Gel-HA) using biomineralization and chemical crosslinking. The impact on periodontal tissue regeneration is assessed by evaluating macrophage immune response and osteogenic differentiation potential of periodontal ligament stem cells (PDLSCs) in vitro and rat periodontal defects in vivo. The jejunum segment, with the highest collagen type I content, is optimal for SIS preparation. SIS retains collagen fiber structure and bioactive factors. Calcium content is 2.21% in SIS-HA and 2.45% in SIS-Gel-HA, with no significant differences in hydrophilicity, physicochemical properties, protein composition, or biocompatibility among SIS, SIS-HA, SIS-Gel, and SIS-Gel-HA. SIS is found to upregulate M2 marker expression, both SIS-HA and SIS-Gel-HA enhance the osteogenic differentiation of PDLSCs through the BMP-2/Smad signaling pathway, and SIS-HA demonstrates superior in vitro osteogenic activity. In vivo, SIS-HA and SIS-Gel-HA yield denser, more mature bones with the highest BMP-2 and Smad expression. SIS-HA and SIS-Gel-HA demonstrate enhanced immunity-osteogenesis coupling, representing a promising periodontal tissue regeneration approach.

Divergent patterns and drivers of leaf functional traits of Robinia pseudoacacia and Pinus tabulaeformis plantations along a precipitation gradient in the Loess plateau, China.

Changes in precipitation patterns in arid and semi-arid regions can reshape plant functional traits and significantly affect ecosystem functions. However, the synchronous responses of leaf economical, anatomical, photosynthetic, and biochemical traits to precipitation changes and their driving factors have rarely been investigated, which hinders our understanding of plants' ecological adaptation strategies to drought tolerance in arid areas. Therefore, the leaf traits of two typical plantations (Robinia pseudoacacia, RP and Pinus tabulaeformis, PT) along the precipitation gradient in the Loess Plateau, including economical, anatomical, photosynthetic, and biochemical traits, were investigated in this study. The results show that the leaf photosynthetic traits of RP and PT increase along the precipitation gradient, whereas leaf biochemical traits decrease. The anatomical traits of PT decrease with increasing precipitation, whereas no significant variation was observed for RP. Random Forest analysis show that LNC, LDMC, Chl, and PRO are leaf traits that significantly vary with the precipitation gradient in both plantations. Correlation analysis reveals that the traits coordination of RP is better than that of PT. The LMG model was used to determine driving factors. The results suggest that MAP explains the variation of PT leaf traits better (30.38%-36.78%), whereas SCH and SPH contribute more to the variation of RP leaf traits (20.88%-41.76%). In addition, the piecewise Structural Equation Model shows that the climate and soil physical and chemical properties directly affect the selected leaf functional traits of RP, whereas only the soil chemical properties directly affect the selected leaf functional traits of PT. The results of this study contribute to the understanding of the ecological adaptation of plants to environmental gradients and highlight that correlations among leaf traits should be considered when predicting plant adaptation strategies under future global change scenarios.

A Novel Magnetic Manipulation Promotes Directional Growth of Periodontal Ligament Stem Cells.

Periodontium is the rally of soft and hard tissues, which will be devastated continuously by the compromise of periodontitis. Current periodontal therapeutic methods cannot effectively reconstruct periodontal ligament (PDL), which is oriented at an angle with tooth root and combined hard tissues to form cementum-PDL-alveolar bone complex. Hence, it is urgent to find new techniques for PDL reconstruction to achieve functional regeneration of periodontium. Herein, we developed a novel method to manipulate the distribution and growth of periodontal ligament stem cells (PDLSCs) by utilizing highly paralleled static magnetic field (SMF) and magnetic nanoparticles (MNPs). PDLSCs were incubated with MNPs in vitro to label with them. Meanwhile, CCK8 and live/dead cell staining assay were used to detect the impact of SMF and MNPs on cell viability. The directional migration and growth of PDLSCs were visualized under microscope. Furthermore, real-time quantitative PCR and western blot were utilized to calculate the expression level of PDL-related genes. The results showed that PDLSCs could rapidly take up MNPs without compromising cell proliferation and viability, consequently endowed with the ability to respond via magnetic force. The cell migration analysis indicated that PDLSCs could move along the magnetic induction line, testifying that SMF exerted forces on PDLSCs that labeled with MNPs. It was demonstrated that collective application of SMF and MNPs not only induced PDLSCs organized and grew directionally, but also initiated elongation of cells and nucleus. Furthermore, the morphological alteration of the nucleus could also effectively enhance the gene and protein expression of Collagen Ⅰα2, Collagen Ⅲ, and Periostin, suggesting the capability of PDLSCs to differentiate into PDL. In conclusion, this study exhibits a new approach for directional reconstruction of PDL to obtain physiological and functional regeneration of periodontium. The Clinical Trial Registration number: WCHSIRB-D-2022-458.

CRISPR-based diagnostics of different biomolecules from nucleic acids, proteins, and small molecules to exosomes.

CRISPR-based detection technologies have been widely explored for molecular diagnostics. However, the challenge lies in converting the signal of different biomolecules, such as nucleic acids, proteins, small molecules, exosomes, and ions, into a CRISPR-based nucleic acid detection signal. Understanding the detection of different biomolecules using CRISPR technology can aid in the development of practical and promising detection approaches. Unfortunately, existing reviews rarely provide an overview of CRISPR-based molecular diagnostics from the perspective of different biomolecules. Herein, we first introduce the principles and characteristics of various CRISPR nucleases for molecular diagnostics. Then, we focus on summarizing and evaluating the latest advancements in CRISPR-based detection of different biomolecules. Through a comparison of different methods of amplification and signal readout, we discuss how general detection methods can be integrated with CRISPR. Finally, we conclude by identifying opportunities for the improvement of CRISPR in quantitative, amplification-free, multiplex, all-in-one, and point-of-care testing (POCT) purposes.

Periostin plays a key role in maintaining the osteogenic abilities of dental follicle stem cells in the inflammatory microenvironment.

OBJECTIVE: This study aimed to explore the effect of periostin in the osteogenic abilities of dental follicle stem cells (DFSCs) and DFSC sheets in the inflammatory microenvironment. DESIGN: DFSCs were isolated from dental follicles and identified. A lentiviral vector was used to knock down periostin in DFSCs. 250 ng/ml lipopolysaccharide from Porphyromonas gingivalis (P.g-LPS) was used to construct the inflammatory microenvironment. Osteogenic differentiation was evaluated by alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot. The formation of extracellular matrix was assessed by qRT-PCR and immunofluorescence. The expressions of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) were measured by western blot. RESULTS: Knockdown of periostin inhibited osteogenic differentiation and promoted adipogenic differentiation of DFSCs. In an inflammatory microenvironment, knockdown of periostin attenuated the proliferation and osteogenic differentiation of DFSCs. Knockdown of periostin inhibited the formation of extracellular matrix collagen I (COL-I), fibronectin, and laminin in DFSC sheets, but did not affect the expression of osteogenesis-related markers alkaline phosphatase (ALP) and osteocalcin (OCN). In the inflammatory microenvironment, knocking down periostin inhibited the expression of OCN and OPG in DFSC sheets, and promoted the expression of RANKL. CONCLUSION: Periostin played a key role in maintaining the osteogenic abilities of DFSCs and DFSC sheets in the inflammatory microenvironment and might be an important molecule in the process of DFSCs coping with inflammatory microenvironment and promoting periodontal tissues regeneration.

Circular RNA hsa_circ_0084054 promotes the progression of periodontitis with diabetes via the miR-508-3p/PTEN axis.

BACKGROUND AND OBJECTIVE: Diabetes is an important risk factor for periodontitis, and circular RNA (circRNA) may play an important role in aggravating inflammation and accelerating disease progression by regulating miRNA/mRNA. This study aimed to investigate the role and mechanism of the hsa_circ_0084054/miR-508-3p/PTEN axis in the progression of periodontitis with diabetes. METHODS: First, circRNA sequencing was used to screen the differentially expressed circRNAs of periodontal ligament cells (PDLCs) treated with high glucose and/or Porphyromonas gingivalis lipopolysaccharide (LPS) in vitro, and the overtly differentially expressed hsa_circ_0084054 was selected and was also verified in periodontal ligament (PDL) tissue from periodontitis patients with diabetes. Then, its ring structure was tested by Sanger sequencing, RNase R, and actinomycin D assays. The bioinformatics analysis, dual luciferase reporter assay, and RIP assay were used to explore the interaction of hsa_circ_0084054/miR-508-3p/PTEN axis, whose effects on inflammation, oxidative stress, and apoptosis of PDLCs were evaluated through the measurement of inflammatory factors, reactive oxygen species (ROS), total superoxide dismutase (SOD), malondialdehyde (MDA), and Annexin V/PI assay. RESULTS: By high-throughput sequencing, it was found that hsa_circ_0084054 was significantly increased in HG + LPS group compared with control group and LPS group, which was also verified in periodontal ligament (PDL) tissue from periodontitis patients with diabetes. Silencing hsa_circ_0084054 in PDLCs decreased the expression of inflammatory factors (IL-1ß, IL-6, TNF-α), the levels of ROS and MDA, and the proportion of apoptotic cells; conversely, SOD activity was enhanced. In addition, we found that hsa_circ_0084054 could up-regulate the expression of PTEN through sponge miR-508-3p to inhibit AKT phosphorylation, finally trigger the aggravation of oxidative stress and inflammation in periodontitis patients with diabetes. CONCLUSION: hsa_circ_0084054 can aggravate inflammation and promote the progression of periodontitis with diabetes by regulating miR-508-3p/PTEN signaling axis, which may serve as a new target for the intervention of periodontitis with diabetes.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

Rapid and Accurate Detection of SARS-CoV-2 Using an iPad-Controlled, High-Throughput, Portable, and Multiplex Hive-Chip Platform (HiCube).

Rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the most effective measures to control the coronavirus disease 2019 (COVID-19) pandemic. However, there is still lack of an ideal detection platform capable of high sample throughput, portability, and multiplicity. Herein, by combining Hive-Chip (capillary microarray) and reverse transcriptional loop-mediated isothermal amplification (RT-LAMP), we developed an iPad-controlled, high-throughput (48 samples at one run), portable (smaller than a backpack), multiplex (monitoring 8 gene fragments in one reaction), and real-time detection platform for SARS-CoV-2 detection. This platform is composed of a portable Hive-Chip device (HiCube; 32.7 × 29.7 × 20 cm, 5 kg), custom-designed software, and optimized Hive-Chips. RT-LAMP primers targeting seven SARS-CoV-2 genes (S, E, M, N, ORF1ab, ORF3a, and ORF7a) and one positive control (human RNase P) were designed and prefixed in the Hive-Chip. On-chip RT-LAMP showed that the limit of detection (LOD) of SARS-CoV-2 synthetic RNAs is 1 copy/µL, and there is no cross-reaction among different target genes. The platform was validated by 100 clinical samples of SARS-CoV-2, and the results were highly consistent with those of the traditional real-time PCR assay. In addition, on-chip detection of 6 other respiratory pathogens showed no cross-reactivity. Overall, our platform has great potential for fast, accurate, and on-site detection of SARS-CoV-2.

Dental Follicle Stem Cells Promote Periodontal Regeneration through Periostin-Mediated Macrophage Infiltration and Reprogramming in an Inflammatory Microenvironment.

Dental follicle stem cells (DFSCs) have been verified to promote periodontal regeneration in an inflammatory microenvironment. When coping with inflammatory stimulation, DFSCs highly express periostin, a bioactive molecule closely related to periodontal homeostasis. It is worth exploring whether and how periostin plays a role in the promotion of periodontal regeneration by DFSCs. By tracking the fate of DFSCs, it was found that DFSCs significantly contributed to periodontal regeneration in rat periodontal defects while they had a low survival rate. They highly expressed periostin and improved the immune microenvironment in the defect area, especially via the recruitment and reprogramming of macrophages. Silencing periostin attenuated the effects of DFSCs in promoting periodontal regeneration and regulating macrophages. Recombinant human periostin (rhPeriostin) could not only directly promote macrophage reprogramming through the integrin αM/phosphorylated extracellular signal-regulated kinase (p-Erk)/Erk signaling pathway, but it also exhibited the potential to promote periodontal regeneration in rats when loaded in a collagen matrix. These results indicated that periostin is actively involved in the process by which DFSCs promote periodontal regeneration through the regulation of macrophages and is a promising molecular agent to promote periodontal regeneration. This study provides new insight into the mechanism by which DFSCs promote periodontal regeneration and suggests a new approach for periodontal regeneration therapy.

Mechanisms and clinical application potential of mesenchymal stem cells-derived extracellular vesicles in periodontal regeneration.

Periodontitis is a high prevalence oral disease which damages both the hard and soft tissue of the periodontium, resulting in tooth mobility and even loss. Existing clinical treatment methods cannot fully achieve periodontal tissue regeneration; thus, due to the unique characteristics of mesenchymal stem cells (MSCs), they have become the focus of attention and may be the most promising new therapy for periodontitis. Accumulating evidence supports the view that the role of MSCs in regenerative medicine is mainly achieved by the paracrine pathway rather than direct proliferation and differentiation at the injured site. Various cells release lipid-enclosed particles known as extracellular vesicles (EVs), which are rich in bioactive substances. In periodontitis, EVs play a pivotal role in regulating the biological functions of both periodontal tissue cells and immune cells, as well as the local microenvironment, thereby promoting periodontal injury repair and tissue regeneration. As a cell-free therapy, MSCs-derived extracellular vesicles (MSC-EVs) have some preponderance on stability, immune rejection, ethical supervision, and other problems; therefore, they may have a broad clinical application prospect. Herein, we gave a brief introduction to MSC-EVs and focused on their mechanisms and clinical application in periodontal regeneration.

Dental follicle cells-derived small extracellular vesicles inhibit pathogenicity of Porphyromonas gingivalis.

OBJECTIVE: It aims to explore the effect of dental follicle cells-derived small extracellular vesicles (D-sEVs) with or without lipopolysaccharides (LPS) pretreating on the pathogenicity of Porphyromonas gingivalis (P. gingivalis). METHODS: The antibacterial effects of D-sEV were evaluated by measuring the growth, biofilm formation, gingipains, and type IX secretion system (T9SS) expression of P. gingivalis. And the influence of D-sEV on P. gingivalis adhesion, invasion, cytotoxicity, and host immune response was examined in gingival epithelial cells (GECs). Then P. gingivalis treated with D-sEV was applied to investigate the pathogenicity in experimental periodontitis of mice. RESULTS: It showed that both D-sEV and P. gingivalis LPS-pretreated D-sEV (L-D-sEV) could target P. gingivalis, inhibit their growth and biofilm formation, and hinder the attachment and invasion in GECs, therefore remarkably decreasing P. gingivalis cytotoxicity and the expression of IL-1ß and IL-6 in GECs. In addition, they significantly reduced the expression of P. gingivalis virulence factors (gingipains and T9SS). In vivo, it showed that the bacteria in the gingiva were significantly decreased after sEV treatment. Meanwhile, less bone loss and fewer inflammatory cells infiltration and osteoclast formation in D-sEV and L-D-sEV groups. CONCLUSION: Both D-sEV and L-D-sEV were proven to inhibit the pathogenicity of P. gingivalis and thus prevented the development of periodontitis.

Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats.

To investigate the effects of growth hormone (GH) on pubertal obese male rats, a rat model of high-fat diet-induced obesity was established in juvenile male rats. The model rats were divided into the treatment group (GH) and the non-treatment group (physiological saline). After 4 weeks, we measured the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), estrogen (E2), testosterone (T), and insulin-like growth factor (IGF-1). The morphological changes of the liver and testis were assessed, and the expression of aromatase was detected. The levels of ALT, AST, TC, TG, LDL-C, E2, and IGF-1 in the treatment group were significantly lower than in the non-treated model rats (P < 0.001). The levels of HDL-C and T of GH-treated rats were significantly higher than those of the non-treatment group (P < 0.001). Compared with non-treated model rats, GH-treated model rats showed reduced liver steatosis, improved morphological structure of the testicular seminiferous tubules, and an increased number of spermatogenic cells. The treatment group also showed lower expression of aromatase in the liver and testis compared with the non-treatment group. GH partially protected pubertal male rats from obesity-induced lipid metabolic disorder and sexual retardation.

Assessment of early wound healing, pain intensity, quality of life and related influencing factors during periodontal surgery: a cross-sectional study.

BACKGROUND: This cross-sectional study assessed early wound healing, pain intensity, quality of life, surgical satisfaction, and related factors during periodontal surgery. METHODS: A total of 369 patients completed the questionnaire before undergoing periodontal surgery (baseline), immediately after the operation (phase I), on the day of suture removal (phase II), and one month later (phase III). The Early Wound Healing Score (EHS) was assessed, and the short-form McGill Pain Questionnaire (SF-MPQ), tooth hypersensitivity visual analog scale (VAS), oral health-related quality of life measure (OHQoL-UK), and surgical satisfaction VAS were administered and analysed. RESULTS: The EHS was 8.41 ± 2.74 and was influenced by disease severity and surgical factors. Scores on the SF-MPQ, pain intensity scores, and OHQoL-UK scores were significantly increased in phase I and decreased later. Tooth sensitivity decreased significantly one month after periodontal surgery. Psychological factors were positively related to SF-MPQ, pain intensity, OHQoL-UK and tooth sensitivity VAS scores in all phases, while disease severity and surgical factors were only related to these scores at baseline or in phases I/II/III. Surgical acceptance and reoperation willingness continuously decreased after surgery, and all these scores were related to surgical satisfaction. CONCLUSIONS: EHS, pain intensity and quality of life were closely related to disease severity, psychological factors and surgical factors in phase I (i.e., immediately after surgery). The findings suggest that surgical details should be enhanced and that behavioural and psychological interventions measures should be implemented to improve outcomes during periodontal operation and during the early postoperative period as well as to improve patient-oriented periodontal surgery experiences. Trial registration This cross-sectional study did not include interventions with human participants, and all the experimental procedures involving humans in this study were approved by the Ethics Committee of West China College of Stomatology, Sichuan University (WCHSIRB-D-2020-284).

Age- and Severity-Associated Humoral Immunity Response in COVID-19 Patients: A Cohort Study from Wuhan, China.

Age has been found to be the single most significant factor in COVID-19 severity and outcome. However, the age-related severity factors of COVID-19 have not been definitively established. In this study, we detected SARS-CoV-2-specific antibody responses and infectious disease-related blood indicators in 2360 sera from 783 COVID-19 patients, with an age range of 1−92 years. In addition, we recorded the individual information and clinical symptoms of the patients. We found that the IgG responses for S1, N, and ORF3a and the IgM for NSP7 were associated with severe COVID-19 at different ages. The IgM responses for the S-protein peptides S1-113 (aa 673−684) and S2-97 (aa 1262−1273) were associated with severe COVID-19 in patients aged <60. Furthermore, we found that the IgM for S1-113 and NSP7 may play a protective role in patients aged <60 and >80, respectively. Regarding clinical parameters, we analyzed the diagnostic ability of five clinical parameters for severe COVID-19 in six age groups and identified three-target panel, glucose, IL-6, myoglobin, IL-6, and NT proBNP as the appropriate diagnostic markers for severe COVID-19 in patients aged <41, 41−50, 51−60, 61−70, 71−80, and >80, respectively. The age-associated severity factors revealed here will facilitate our understanding of COVID-19 immunity and diagnosis, and eventually provide meaningful information for combating the pandemic.

Advances of Hydrogel Therapy in Periodontal Regeneration-A Materials Perspective Review.

Hydrogel, a functional polymer material, has emerged as a promising technology for therapies for periodontal diseases. It has the potential to mimic the extracellular matrix and provide suitable attachment sites and growth environments for periodontal cells, with high biocompatibility, water retention, and slow release. In this paper, we have summarized the main components of hydrogel in periodontal tissue regeneration and have discussed the primary construction strategies of hydrogels as a reference for future work. Hydrogels provide an ideal microenvironment for cells and play a significant role in periodontal tissue engineering. The development of intelligent and multifunctional hydrogels for periodontal tissue regeneration is essential for future research.

Identification of sitagliptin binding proteins by affinity purification mass spectrometry.

Type 2 diabetes mellitus (T2DM) is recognized as a serious public health concern with increasing incidence. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin has been used for the treatment of T2DM worldwide. Although sitagliptin has excellent therapeutic outcome, adverse effects are observed. In addition, previous studies have suggested that sitagliptin may have pleiotropic effects other than treating T2DM. These pieces of evidence point to the importance of further investigation of the molecular mechanisms of sitagliptin, starting from the identification of sitagliptin-binding proteins. In this study, by combining affinity purification mass spectrometry (AP-MS) and stable isotope labeling by amino acids in cell culture (SILAC), we discover seven high-confidence targets that can interact with sitagliptin. Surface plasmon resonance (SPR) assay confirms the binding of sitagliptin to three proteins, i. e., LYPLAL1, TCP1, and CCAR2, with binding affinities (K D) ranging from 50.1 µM to 1490 µM. Molecular docking followed by molecular dynamic (MD) simulation reveals hydrogen binding between sitagliptin and the catalytic triad of LYPLAL1, and also between sitagliptin and the P-loop of ATP-binding pocket of TCP1. Molecular mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis indicates that sitagliptin can stably bind to LYPLAL1 and TCP1 in active sites, which may have an impact on the functions of these proteins. SPR analysis validates the binding affinity of sitagliptin to TCP1 mutant D88A is ~10 times lower than that to the wild-type TCP1. Our findings provide insights into the sitagliptin-targets interplay and demonstrate the potential of sitagliptin in regulating gluconeogenesis and in anti-tumor drug development.