Morphological and functional characterization of circulating hemocytes in Tribolium castaneum larvae.

Hemocytes are pivotal in the immune response of insects against invasive pathogens. However, our knowledge of hemocyte types and their specific function in Tribolium castaneum, an increasingly important Coleoptera model insect in various research fields, remains limited. Presently, a combination of morphological criteria and dye-staining properties were used to characterize hemocyte types from T. castaneum larvae, and 4 distinct types were identified: granulocytes, oenocytoids, plasmatocytes and prohemocytes. Following different immune challenges, the total hemocyte counts declined rapidly in the initial phase (at 2 h), then increased over time (at 4 and 6 h) and eventually returned to the naive state by 24 h post-injection. Notably, the morphology of granulocytes underwent dramatic changes, characterized by an expansion of the surface area and an increased production of pseudopods, and with the number of granulocytes rising significantly through mitotic division. Granulocytes and plasmatocytes, the main hemocyte types in T. castaneum larvae, can phagocytose bacteria or latex beads injected into the larval hemolymph in vivo. Furthermore, these hemocytes participate in the encapsulation and melanization processes in vitro, forming capsules to encapsulate and melanize nickel-nitrilotriacetic acid (Ni-NTA) beads. This study provides the first comprehensive characterization of circulating hemocytes in T. castaneum larvae, offering valuable insights into cell-mediated immunity in response to bacterial infection and the injection of latex beads. These results deepen our understanding of the cellular response mechanisms in T. castaneum larvae and lay a solid foundation for subsequent investigations of the involvement of T. castaneum hemocytes in combating pathogens.

Novel regulation pathway of eclosion hormones in Tribolium castaneum by distinct transcription factors through the initiation of 20-Hydroxyecdysone.

Eclosion hormone (EH) is not only a key trigger of insect ecdysis, but is also involved in the regulation of important physiological processes such as development, diapause, metamorphosis and reproduction. EH is an ideal target for RNAi treatment and prevention of the Tribolium castaneum. However, two EH genes in Tribolium castaneum demonstrate distinct replication and functional conversion relationships, and the mechanisms of transcriptional regulation of eclosion hormone remain largely unexplored and poorly understood. In this study, the activity of highly active promoter fragments and potential transcription factors of TcEH and TcEHL were identified using the Dual-Luciferase reporter system and TANSFAC. TcSlbo and TcCAD were revealed to be important transcription factors for TcEH and TcEHL, respectively. Knockdown of TcSlbo failed to slough off the old epidermis of Tribolium castaneum and prevented them from developing into adults. Furthermore, we demonstrated for the first time that 20-hydroxyecdysone (20E) affects the expression of TcEH and TcEHL by regulating the transcriptional activities of TcSlbo and TcCAD. This study provides new insights into the transcription regulation of TcEH and TcEHL, their roles in insect growth and development, and the involvement of 20E in eclosion regulation, offering potential molecular targets for future pest management strategies.

Evaluation of transmission-blocking potential of PvPSOP25 using transgenic murine malaria parasite and clinical isolates.

BACKGROUND: Malaria transmission-blocking vaccines (TBVs) aim to inhibit malaria parasite development in mosquitoes and prevent further transmission to the human host. The putative-secreted ookinete protein 25 (PSOP25), highly conserved in Plasmodium spp., is a promising TBV target. Here, we investigated PvPSOP25 from P. vivax as a TBV candidate using transgenic murine parasite P. berghei and clinical P. vivax isolates. METHODS AND FINDINGS: A transgenic P. berghei line expressing PvPSOP25 (TrPvPSOP25Pb) was generated. Full-length PvPSOP25 was expressed in the yeast Pichia pastoris and used to immunize mice to obtain anti-rPvPSOP25 sera. The transmission-blocking activity of the anti-rPvPSOP25 sera was evaluated through in vitro assays and mosquito-feeding experiments. The antisera generated by immunization with rPvPSOP25 specifically recognized the native PvPSOP25 antigen expressed in TrPvPSOP25Pb ookinetes. In vitro assays showed that the immune sera significantly inhibited exflagellation and ookinete formation of the TrPvPSOP25Pb parasite. Mosquitoes feeding on mice infected with the transgenic parasite and passively transferred with the anti-rPvPSOP25 sera showed a 70.7% reduction in oocyst density compared to the control group. In a direct membrane feeding assay conducted with five clinical P. vivax isolates, the mouse anti-rPvPSOP25 antibodies significantly reduced the oocyst density while showing a negligible influence on mosquito infection prevalence. CONCLUSIONS: This study supported the feasibility of transgenic murine malaria parasites expressing P. vivax antigens as a useful tool for evaluating P. vivax TBV candidates. Meanwhile, the moderate transmission-reducing activity of the generated anti-rPvPSOP25 sera necessitates further research to optimize its efficacy.

Bone regeneration with hydroxyapatite particles loaded in photo-cross-linkable hydrogel: An experimental study.

This study explores the use of in situ cross-linked hyaluronic acid methacryloyl (HAMA) and hydroxyapatite particles (HAP) for bone defect repair. Human periodontal ligament stem cells (PDLSCs) were isolated and co-cultured with the HAMA-HAP composite. Osteogenic differentiation was evaluated using Alizarin Red staining, alkaline phosphatase activity quantification, and polymerase chain reaction (PCR). A cranial defect was induced in Sprague-Dawley rats. This defect was then filled with the HAMA-HAP composite and cross-linked using UV light exposure. Bone formation was assessed through radiographic and histological analyses. The HAMA-HAP composite was found to promote cell viability similarly to pure HAP. It also enhanced gene expression of ALP, OPN, and Runx2, and increased ALP activity and mineralized nodule formation in vitro. Micro-CT scans showed defect restoration in the HAMA-HAP and HAP groups compared to the control group. The HAMA-HAP group exhibited higher Tb.N, Tb.Sp, Tb.Th, and BV/TV. Masson staining showed the HAMA-HAP composite restored the defect site, with new bone formation thicker than in the HAP group. The HAMA-HAP composite showed excellent biocompatibility and promoted osteogenic differentiation of PDLSCs. It effectively repaired cranial defects, indicating its potential for clinical use in bone defect repair.

Zwitterionic Copolymers for Anti-Scaling Applications in Simulated Spaceflight Wastewater Scenarios.

Water reclamation in spaceflight applications, such as those encountered on the International Space Station (ISS), requires complex engineering solutions to ensure maximum water recovery. Current vapor compression distillation (VCD) technologies are effective but produce highly concentrated brines and often cause scaling within a separation system. This work evaluates initial steps toward integrating pervaporation, a membrane separation process, as a brine management strategy for ISS wastewaters. Pervaporation performs separations driven by a chemical potential difference across the membrane created by either a sweep gas or a vacuum pull. Pervaporation membranes, as with most membrane processes, can be subject to scaling. Therefore, this work studies the anti-scaling properties of zwitterions (polymeric molecules with covalently tethered positive and negative ions) coated onto sulfonated pentablock terpolymer block polymer (Nexar) pervaporation membrane surfaces. We report a method for applying zwitterions to the surface of pervaporation membranes and the effect on performance parameters such as flux and scaling resistance. Membranes with zwitterions had up to 53% reduction in permeance but reduced scaling. The highest amount of scaling occurred in the samples exposed to calcium chloride, and uncoated membranes had weight percent increases as high as 1617 ± 241%, whereas zwitterion-coated membranes experienced only about 317 ± 87% weight increase in the presence of the same scalant.

Flattening the Curve after the Initial Outbreak of Coronavirus Disease 2019: A Data-Driven Modeling Analysis for the Omicron Pandemic in China.

China is relaxing COVID-19 measures from the "dynamic zero tolerance" (DZT) level. The "flatten-the-curve" (FTC) strategy, which decreases and maintains the low rate of infection to avoid overwhelming the healthcare system by adopting relaxed nonpharmaceutical interventions (NPIs) after the outbreak, has been perceived as the most appropriate and effective method in preventing the spread of the Omicron variant. Hence, we established an improved data-driven model of Omicron transmission based on the age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model constructed by Cai to deduce the overall prevention effect throughout China. At the current level of immunity without the application of any NPIs, more than 1.27 billion (including asymptomatic individuals) were infected within 90 days. Moreover, the Omicron outbreak would result in 1.49 million deaths within 180 days. The application of FTC could decrease the number of deaths by 36.91% within 360 days. The strict implementation of FTC policy combined with completed vaccination and drug use, which only resulted in 0.19 million deaths in an age-stratified model, will help end the pandemic within about 240 days. The pandemic would be successfully controlled within a shorter period of time without a high fatality rate; therefore, the FTC policy could be strictly implemented through enhancement of immunity and drug use.

Alterations in histology of the aging salivary gland and correlation with the glandular inflammatory microenvironment.

Aging-related salivary dysfunction typically causes reduced saliva volumes, which leads to debilitating consequences, even affecting patient quality of life. Understanding the respective clinicopathological characteristics and molecular mechanisms underlying salivary gland functioning during aging is vital for therapeutic purposes. Here, we provide a detailed atlas of the salivary gland microenvironment during aging, and we identified several phenotypes characteristic of aging salivary glands, including acini atrophy, increased inflammatory cells, altered immune responses, and accumulation of lysosomes and autophagosomes in aging cells, which may reflect progressive degeneration of salivary gland function. Furthermore, our analyses suggested significant enrichment of metabolic pathways in aging glands. Our results revealed complex cellular cross-talk among aging acinar cells, inflammatory factors, and immune responses. A natural aging animal model was established to verify these findings. This study provides mechanistic insights into age-related clinicopathogenesis, important implications for early diagnosis, and identification of new targets for improving salivary gland dysfunction.

Pollen allergens sensitization characteristics and risk factors among allergy rhinitis of children in mainland China: A multicenter study.

Background: No comprehensive multicenter study of sensitization patterns among patients with allergic rhinitis (AR) to various common pollen allergens was available nationwide, and risks factors of pollen-induced allergic rhinitis (PiAR) in mainland China was unclear. This study aimed to fill this gap. Methods: A multicenter study was performed on 736 AR patients aged below 18 from four regions of mainland China. Patients completed a standardized questionnaire asking for the environmental risk factors and AR severity, and undertook skin prick tests (SPT) with 14 common pollen allergens. Findings: Among the 736 patients, 341 patients (46.33%) suffered at least one positive pollen allergen sensitization. The positive rate of pollen allergens was significantly higher in the high-age group (Damato et al., 2007; Wang et al., 2018; Luo et al., 2016; Demoly et al., 2011; Sampson and Albergo, 1984; Li et al., 2009; Luo et al., 2021; Ziska and Beggs, 2011; Melén et al., 2020; Jensen-Jarolim, 2017; Rönmark et al., 2017; Ge et al., 2017) [6-17] than the low-age group ( ≤ 5), while no significant difference was found between the sexes. The sensitizations to pollen allergens varied widely among four geographical areas. The positive rate was higher in north China and west China than in east China, and south China had the lowest positive rate. The region of residence, ages, ethnic minorities, history of pollen exposure, the material of living room floor and material of pillow were statistically significant risks of PiAR. Interpretation: This study provides new insights into the pollen allergens sensitization characteristics in AR and the factors affecting PiAR in mainland China.

Oxidative stress: The nexus of obesity and cognitive dysfunction in diabetes.

Obesity has been associated with oxidative stress. Obese patients are at increased risk for diabetic cognitive dysfunction, indicating a pathological link between obesity, oxidative stress, and diabetic cognitive dysfunction. Obesity can induce the biological process of oxidative stress by disrupting the adipose microenvironment (adipocytes, macrophages), mediating low-grade chronic inflammation, and mitochondrial dysfunction (mitochondrial division, fusion). Furthermore, oxidative stress can be implicated in insulin resistance, inflammation in neural tissues, and lipid metabolism disorders, affecting cognitive dysfunction in diabetics.

Is antenatal or early-life vitamin D associated with eczema or food allergy in childhood? A systematic review.

OBJECTIVE: To summarise the associations between antenatal or early-life blood vitamin D and the development of eczema/food allergy in childhood. DESIGN: A systematic review and meta-analyses were conducted to synthesize the published literature. Two reviewers independently performed the study selection and data extraction on Covidence. We assessed the risk of bias for observational studies by using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool for clinical trials. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). DATA SOURCES: We systematically searched PubMed and Embase from inception and April 2022. ELIGIBILITY CRITERIA: Human studies that investigated prospective associations between antenatal or early-life blood vitamin D levels, dietary intake or supplementation and childhood eczema/food allergy. RESULTS: Forty-three articles including six randomised controlled trials (RCTs) were included. Four RCTs of vitamin D supplementation during pregnancy showed no evidence of an effect on the incidence of eczema (pooled odds ratio [OR] = 0.85; 0.67-1.08, I2  = 6.7%, n = 2074). Three RCTs reported null associations between supplementation in pregnancy/infancy and food allergy. From six cohort studies, increasing cord blood vitamin D levels were associated with reduced prevalence of eczema at/close to age one (OR per 10 nmol/L increase = 0.89; 0.84-0.94, I2  = 0%, 2025 participants). We found no evidence of an association between maternal antenatal or infant vitamin D level or dietary intake and the development of food allergy or eczema in offspring. CONCLUSIONS: We found an association between higher vitamin D levels in cord blood and reduced risk of eczema in cohort studies. Further trials with maternal and infant supplementation are needed to confirm if vitamin D supplementation can effectively prevent eczema or food allergy in childhood. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, No. CRD42013005559.

Investigation of zeolite H-ß effect on pyrolysis of polystyrene by multiple kinetic analysis methods.

For studying the effects of H-ß zeolite on the pyrolysis of polystyrene (PS), non-isothermal thermogravimetric measurements were conducted in N2 under 5, 10, 15, and 20 K/min. The results show that the addition of 10 ~ 30 wt.% H-ß zeolite can significantly decrease the initial pyrolysis temperature of PS, indicative of the catalytic effect of zeolite used. Through kinetic analysis of the pyrolysis of PS blends, the isoconversional activation energies are calculated to be 121.8 ~ 191.9, 92.1 ~ 173.8, and 116.7 ~ 192.4 kJ/mol for the PS blends with zeolite loading of 10, 20, and 30 wt.%, respectively. Meanwhile, the pyrolysis degradation functions are determined through the Master-plots method integrated with a recently developed compensation-effect method to follow chemical reaction mechanism with the reaction order of 0.9, 1.0, and 0.6 for PS/zeolite blends of 10, 20, and 30 wt.% loading, and their pre-exponential factors are respectively calculated to be 6.18 × 108 ~ 5.71 × 1011, 2.36 × 106 ~ 9.23 × 1011, and 8.38 × 107 ~ 1.11 × 1012 min-1. Our work may provide some insights for how to better describe experimental results with theoretical predications and necessary information for performing any potential pyrolysis designs.

Reply to Chan et al.

We agree that smoking might be a risk factor for the severity of COVID-19, but in our previous study, smoking was not so robust compared with our conclusion. Also, we strongly agreed that COVID-19 patients with diabetes or other chronic diseases might worsen the situation of the disease. But these factors were out of the scope of our study and we had published other research on this topic related to diabetes. Because of the limited sample size and original medical records, our study could not cover many factors. But we wish our study will be a useful and meaningful pilot study for future studies.

Nicotinamide Mononucleotide Alleviates Osteoblast Senescence Induction and Promotes Bone Healing in Osteoporotic Mice.

Combating the accumulated senescent cells and the healing of osteoporotic bone fractures in the older remains a significant challenge. Nicotinamide mononucleotide (NMN), a precursor of NAD+, is an excellent candidate for mitigating aging-related disorders. However, it is unknown if NMN can alleviate senescent cell induction and enhance osteoporotic bone fracture healing. Here we show that NMN treatment partially reverses the effects of tumor necrosis factor-alpha (TNF-α) on human primary osteoblasts (HOBs): senescent cell induction, diminished osteogenic differentiation ability, and intracellular NAD+ and NADH levels. Mechanistically, NMN restores the mitochondrial dysfunction in HOBs induced by TNF-α evidenced by increased mitochondrial membrane potential and reduced reactive oxidative species and mitochondrial mass. NMN also increases mitophagy activity by down-regulating P62 expression and up-regulating light chain 3B-II protein expression. In addition, the cell senescence protective effects of NMN on HOBs are mitigated by a mitophagy inhibitor (Bafilomycin A1). In vivo, NMN supplementation attenuates senescent cell induction in growth plates, partially prevents osteoporosis in an ovariectomized mouse model, and accelerates bone healing in osteoporotic mice. We conclude that NMN can be a novel and promising therapeutic candidate to enhance bone fracture healing capacity in the older.

Association between multiple meteorological variables and seasonal influenza A and B virus transmission in Macau.

Few studies have evaluated the influence of meteorological variables on different influenza types in subtropical regions. This study aimed to explore the association between meteorological variables and the onset of influenza A (Flu-A) and B (Flu-B) in Macau. Daily influenza case data in Macau were collected from Kiang Wu Hospital from 1 January, 2014 to 31 December, 2018. Daily meteorological data were obtained from the Macau Meteorological Service. The distributed lag non-linear model (DLNM) was used to estimate the effects of meteorological variables on seasonal influenza outbreaks. Regarding mean air temperature (temp), the peaks of the cumulative relative risks (RRs) of Flu-A and Flu-B were both at 4.0 °C and 28.0 °C. Regarding the diurnal temperature range (DTR), the peaks of the cumulative RR of Flu-A were at 1.0 °C and 5.0 °C, while the cumulative RR of Flu-B increased as the DTR decreased. The association between influenza risks and relative humidity (RH) showed a U-shape curve. The risk of influenza increased when the RH was below 50% or above 90%. The risk of both types of influenza increased significantly when the sunshine duration (SD) was below 3.5 h. Taking the median value as the reference, a significant cold effect was observed over 16-24 days lag for Flu-A. Lag effects were found for both types of influenza in low-DTR, and humid and short SD conditions. This study revealed complex non-linear association between meteorological variables and the different influenza types in Macau.

Chondrogenic potential of manganese-loaded composite scaffold combined with chondrocytes for articular cartilage defect.

Cartilage is an alymphatic, avascular and non-innervated tissue. Lack of potential regenerative capacity to reconstruct chondral defect has accelerated investigation and development of new strategy for cartilage repair. We prepared a manganese ion-incorporated natupolymer-based scaffold with chitosan-gelatin by freeze-drying procedure. The scaffold was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, energy dispersive spectroscopy, compressive testing, and analysis of porosity and flexibility. Live/dead assay confirmed the good cytocompatibility of prepared scaffold on rat articular chondrocytes after 10 days and 4 weeks of culture. The manganese-loaded composite scaffold upregulated the expression of chondrogenic-related markers (Sox9, integrin, and Col II) in chondrocytes. Western blot analysis of proteins extracted from chondrocytes grown on scaffolds indicated the signaling pathways of p-Akt and p-ERK1/2 played a key role. Histological analysis following implantation of current composite scaffold loaded with chondrocytes into a rat articular cartilage defect model showed that the scaffolds promoted the formation of collagen II and cartilage repair. These findings suggested the potential of manganese-loaded scaffold to promote new cartilage formation and a promising strategy for articular cartilage engineering application.

Incorporation of Suppression of Tumorigenicity 2 into Random Survival Forests for Enhancing Prediction of Short-Term Prognosis in Community-ACQUIRED Pneumonia.

(1) Background: Biomarker and model development can help physicians adjust the management of patients with community-acquired pneumonia (CAP) by screening for inpatients with a low probability of cure early in their admission; (2) Methods: We conducted a 30-day cohort study of newly admitted adult CAP patients over 20 years of age. Prognosis models to predict the short-term prognosis were developed using random survival forest (RSF) method; (3) Results: A total of 247 adult CAP patients were studied and 208 (84.21%) of them reached clinical stability within 30 days. The soluble form of suppression of tumorigenicity-2 (sST2) was an independent predictor of clinical stability and the addition of sST2 to the prognosis model could improve the performance of the prognosis model. The C-index of the RSF model for predicting clinical stability was 0.8342 (95% CI, 0.8086-0.8598), which is higher than 0.7181 (95% CI, 0.6933-0.7429) of CURB 65 score, 0.8025 (95% CI, 0.7776-8274) of PSI score, and 0.8214 (95% CI, 0.8080-0.8348) of cox regression. In addition, the RSF model was associated with adverse clinical events during hospitalization, ICU admissions, and short-term mortality; (4) Conclusions: The RSF model by incorporating sST2 was more accurate than traditional methods in assessing the short-term prognosis of CAP patients.

The clinical and bioinformatics analysis for the role of antihypertension drugs on mortality among patients with hypertension hospitalized with COVID-19.

Comorbidities such as hypertension could exacerbate symptoms of coronaviral disease 2019 (COVID)-19 infection. Patients with hypertension may receive both anti-COVID-19 and antihypertension therapies when infected with COVID-19. However, it is not clear how different classes of anti-hypertension drugs impact the outcome of COVID-19 treatment. Herein, we explore the association between the inpatient use of different classes of anti-hypertension drugs and mortality among patients with hypertension hospitalized with COVID-19. We totally collected data from 278 patients with hypertension diagnosed with COVID-19 admitted to hospitals in Wuhan from February 1 to April 1, 2020. A retrospective study was conducted and single-cell RNA-sequencing (RNA-Seq) analysis of treatment-related genes was performed. The results showed that Angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) drugs significantly increased the survival rate but the use of angiotensin-converting enzyme inhibitor/ß-block/diuretic drugs did not affect the mortality caused by COVID-19. Based on the analysis of four public data sets of single-cell RNA-Seq on COVID-19 patients, we concluded that JUN, LST1 genes may play a role in the effect of ARB on COVID-19-related mortality, whereas CALM1 gene may contribute to the effect of CCB on COVID-19-related mortality. Our results provide guidance on the selection of antihypertension drugs for hypertensive patients infected with COVID-19.

Target-triggered tertiary amplifications for sensitive and label-free protein detection based on lighting-up RNA aptamer transcriptions.

Proteins play vital roles in regulating a series of living activities and can be potentially considered to be useful indicators for diagnosing various diseases. Here, a target-triggered transcription cascade amplification strategy with the use of the fluorescence switch-on RNA aptamer is constructed for label-free and sensitive platelet-derived growth factor-BB (PDGF-BB) protein biomarker detection. The target molecule of PDGF-BB binds a rationally designed multifunctional hairpin probe to switch its structure and to expose a primer binding region. The primer sequence further binds such a region to initiate the target recycling and lighting-up RNA aptamer transcription cascade cycles to yield tremendous RNA aptamers. And, the fluorescence of the organic dye is substantially enhanced upon binding to these RNA aptamers for realizing highly sensitive and label-free PDGF-BB detection with the detection limit being lowered to 0.8 pM. Moreover, the developed strategy has superior selectivity and exhibits a promising potential to detect PDGF-BB spiked into serums with buffer dilution, which makes this method an attractive sensing system for detecting other biomarkers at trace levels.

A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjogren's Syndrome.

Background: Primary Sjogren's syndrome (pSS) is a slowly progressive, inflammatory autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands. It becomes more recognized that morphology alterations of epithelial mitochondria are involved in altered cellular bioenergetics in pSS patients. The integrated analysis of the mitochondrial role in the pathogenesis and aberrant immune microenvironment in pSS remains unknown. Methods: The mitochondria-related genes and gene expression data were downloaded from the MitoMiner, MitoCarta, and NCBI GEO databases. We performed novel transcriptomic analysis and constructed a network between the mitochondrial function and immune microenvironment in pSS-salivary glands by computer-aided algorithms. Subsequently, real-time PCR was performed in clinical samples in order to validate the bioinformatics results. Histological staining and transmission electron microscopy (TEM) were further studied on labial salivary gland samples of non-pSS and pSS patients characterized for mitochondria-related phenotypic observation in the different stages of the disease. Results: The bioinformatic analysis revealed that the expression of several mitochondria-related genes was altered in pSS. Quantitative real-time PCR showed that four hub genes, CD38, CMPK2, TBC1D9, and PYCR1, were differentially expressed in the pSS clinical samples. These hub genes were associated with the degree of immune cell infiltration in salivary glands, the mitochondrial respiratory chain complexes, mitochondrial metabolic pathway in gluconeogenesis, TCA cycle, and pyruvate/ketone/lipid/amino acid metabolism in pSS. Clinical data revealed that the gene expression of fission (Fis1, DRP1, and MFF) and fusion (MFN1, MFN2, and OPA1) was downregulated in pSS samples, consistent with the results from the public validation database. As the disease progressed, cytochrome c and Bcl-2 proteins were regionally distributed in salivary glands from pSS patients. TEM revealed cytoplasmic lipid droplets and progressively swollen mitochondria in salivary epithelial cells. Conclusion: Our study revealed cross talk between mitochondrial dysfunction and the immune microenvironment in salivary glands of pSS patients, which may provide important insights into SS clinical management based on modulation of mitochondrial function.

Biomechanical Assessment of Tilted Mandibular Second Molars with Full-Crown Adjacent to Implant-Supported Restoration: 3D Finite Element Analysis.

Purpose: The aim of this study was to investigate the effects of tooth root inclination and crown preparation angulation on the stress distribution of tilted second molars, supporting structures and adjacent implant by using the finite element analysis method. Materials and Methods: 3D finite element models of tilted second molar and tooth-supporting structures, including the two designs with three different angles of root inclination and crown preparation angulations, were constructed for full-crown restoration. For all models, the stress distribution was analyzed under vertical and oblique loading conditions. Results: The maximum equivalent stress (MES) increased as root inclination increased, and the highest stress value occurred in the tooth root furcation of the model with 30° root inclination under oblique loading. When root inclination was the same, the MES of each structure was approximate under the same direction load regardless of crown preparation angulation. Higher stress values were found on the tooth root, periodontal ligament, and cortical bone of all models under oblique load compared with vertical load. The highest stress value occurred in the distal adjacent area of implant. Conclusion: Tooth roots with less than 30° inclination, occlusal preparation parallel to the bite plane and small oblique force loading are recommended as significant considerations for full-crown restoration of a mesial inclined mandibular second molar.