Predicting lncRNA-disease associations based on combining selective similarity matrix fusion and bidirectional linear neighborhood label propagation.

Recent studies have revealed that long noncoding RNAs (lncRNAs) are closely linked to several human diseases, providing new opportunities for their use in detection and therapy. Many graph propagation and similarity fusion approaches can be used for predicting potential lncRNA-disease associations. However, existing similarity fusion approaches suffer from noise and self-similarity loss in the fusion process. To address these problems, a new prediction approach, termed SSMF-BLNP, based on organically combining selective similarity matrix fusion (SSMF) and bidirectional linear neighborhood label propagation (BLNP), is proposed in this paper to predict lncRNA-disease associations. In SSMF, self-similarity networks of lncRNAs and diseases are obtained by selective preprocessing and nonlinear iterative fusion. The fusion process assigns weights to each initial similarity network and introduces a unit matrix that can reduce noise and compensate for the loss of self-similarity. In BLNP, the initial lncRNA-disease associations are employed in both lncRNA and disease directions as label information for linear neighborhood label propagation. The propagation was then performed on the self-similarity network obtained from SSMF to derive the scoring matrix for predicting the relationships between lncRNAs and diseases. Experimental results showed that SSMF-BLNP performed better than seven other state of-the-art approaches. Furthermore, a case study demonstrated up to 100% and 80% accuracy in 10 lncRNAs associated with hepatocellular carcinoma and 10 lncRNAs associated with renal cell carcinoma, respectively. The source code and datasets used in this paper are available at: https://github.com/RuiBingo/SSMF-BLNP.

Deficiency of FRMD5 results in neurodevelopmental dysfunction and autistic-like behavior in mice.

The pathophysiology of autism spectrum disorders (ASDs) is causally linked to postsynaptic scaffolding proteins, as evidenced by numerous large-scale genomic studies [1, 2] and in vitro and in vivo neurobiological studies of mutations in animal models [3, 4]. However, due to the distinct phenotypic and genetic heterogeneity observed in ASD patients, individual mutation genes account for only a small proportion (<2%) of cases [1, 5]. Recently, a human genetic study revealed a correlation between de novo variants in FERM domain-containing-5 (FRMD5) and neurodevelopmental abnormalities [6]. In this study, we demonstrate that deficiency of the scaffolding protein FRMD5 leads to neurodevelopmental dysfunction and ASD-like behavior in mice. FRMD5 deficiency results in morphological abnormalities in neurons and synaptic dysfunction in mice. Frmd5-deficient mice display learning and memory dysfunction, impaired social function, and increased repetitive stereotyped behavior. Mechanistically, tandem mass tag (TMT)-labeled quantitative proteomics revealed that FRMD5 deletion affects the distribution of synaptic proteins involved in the pathological process of ASD. Collectively, our findings delineate the critical role of FRMD5 in neurodevelopment and ASD pathophysiology, suggesting potential therapeutic implications for the treatment of ASD.

4 mC site recognition algorithm based on pruned pre-trained DNABert-Pruning model and fused artificial feature encoding.

DNA 4 mC plays a crucial role in the genetic expression process of organisms. However, existing deep learning algorithms have shortcomings in the ability to represent DNA sequence features. In this paper, we propose a 4 mC site identification algorithm, DNABert-4mC, based on a fusion of the pruned pre-training DNABert-Pruning model and artificial feature encoding to identify 4 mC sites. The algorithm prunes and compresses the DNABert model, resulting in the pruned pre-training model DNABert-Pruning. This model reduces the number of parameters and removes redundancy from output features, yielding more precise feature representations while upholding accuracy.Simultaneously, the algorithm constructs an artificial feature encoding module to assist the DNABert-Pruning model in feature representation, effectively supplementing the information that is missing from the pre-trained features. The algorithm also introduces the AFF-4mC fusion strategy, which combines artificial feature encoding with the DNABert-Pruning model, to improve the feature representation capability of DNA sequences in multi-semantic spaces and better extract 4 mC sites and the distribution of nucleotide importance within the sequence. In experiments on six independent test sets, the DNABert-4mC algorithm achieved an average AUC value of 93.81%, outperforming seven other advanced algorithms with improvements of 2.05%, 5.02%, 11.32%, 5.90%, 12.02%, 2.42% and 2.34%, respectively.

Regulatory Mechanisms of Quorum Sensing System of Bacteria in Response to Chlorine and Ozone Disinfection.

Waterborne pathogens invariably present considerable threats to public health. The quorum sensing (QS) system is instrumental in coordinating bacterial growth and metabolisms. However, the responses and regulatory mechanisms of bacteria to various disinfection technologies through quorum sensing are still unclear. This study examines the inactivation effect of chlorination and ozonation on biofilms and planktonic cells of QS signaling-deficient mutants of Pseudomonas aeruginosa. Cell counting and viability assessment revealed that the combined disinfection of chlorine and ozone was the most effective for inactivating planktonic P. aeruginosa within 10 min of exposure. Additionally, microfluidic chip culture demonstrated that the secretion of quinolone signals escalated biofilms' disinfection resistance. Disinfection exposure significantly altered the gene expression of wild-type strains and QS signaling-deficient mutants. Moreover, the QS system triggered multilayered gene expression programs as a responsive protection to disinfectant exposure, including oxidative stress, ribosome synthesis, and the nutrient absorption of bacteria. These insights broaden our understanding of bacterial QS in response to disinfection, promising potential strategies toward efficient disinfection processes.

Deciphering the formation of granules by n-DAMO and Anammox microorganisms.

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) process is a promising wastewater treatment technology, but the slow microbial growth rate greatly hinders its practical application. Although high-level nitrogen removal and excellent biomass accumulation have been achieved in n-DAMO granule process, the formation mechanism of n-DAMO granules remains unresolved. To elucidate the role of functional microbes in granulation, this study attempted to cultivate granules dominated by n-DAMO microorganisms and granules coupling n-DAMO with anaerobic ammonium oxidation (Anammox). After long-term operation, dense granules were developed in the two systems where both n-DAMO archaea and n-DAMO bacteria were enriched, whereas granulation did not occur in the other system dominated by n-DAMO bacteria. Extracellular polymeric substances (EPS) measurement indicated the critical role of EPS production in the granulation of n-DAMO process. Metagenomic and metatranscriptomic analyses revealed that n-DAMO archaea and Anammox bacteria were active in EPS biosynthesis, while n-DAMO bacteria were inactive. Consequently, more EPS were produced in the systems containing n-DAMO archaea and Anammox bacteria, leading to the successful development of n-DAMO granules. Furthermore, EPS biosynthesis in n-DAMO systems is potentially regulated by acyl-homoserine lactones and c-di-GMP. These findings not only provide new insights into the mechanism of granule formation in n-DAMO systems, but also hint at potential strategies for management of the granule-based n-DAMO process.

Deep insights into the biofilm formation mechanism and nitrogen-transformation network in a nitrate-dependent anaerobic methane oxidation biofilm.

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) process offers a promising solution for simultaneously achieving methane emissions reduction and efficient nitrogen removal in wastewater treatment. Although nitrogen removal at a practical rate has been achieved by n-DAMO biofilm process, the mechanisms of biofilm formation and nitrogen transformation remain to be elucidated. In this study, n-DAMO biofilms were successfully developed in the membrane aerated moving bed biofilm reactor (MAMBBR) and removed nitrate at a rate of 159 mg NO3--N L-1 d-1. The obvious increase in the content of extracellular polymeric substances (EPS) indicated that EPS production was important for biofilm development. n-DAMO microorganisms dominated the microbial community, and n-DAMO bacteria were the most abundant microorganisms. However, the expression of biosynthesis genes for proteins and polysaccharides encoded by n-DAMO archaea was significantly more active compared to other microorganisms, suggesting the central role of n-DAMO archaea in EPS production and biofilm formation. In addition to nitrate reduction, n-DAMO archaea were revealed to actively express dissimilatory nitrate reduction to ammonium and nitrogen fixation. The produced ammonium was putatively converted to dinitrogen gas through the joint function of n-DAMO archaea and n-DAMO bacteria. This study revealed the biofilm formation mechanism and nitrogen-transformation network in n-DAMO biofilm systems, shedding new light on promoting the application of n-DAMO process.

LUNCRW: Prediction of potential lncRNA-disease associations based on unbalanced neighborhood constraint random walk.

Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are associated with various complex human diseases. They can serve as disease biomarkers and hold considerable promise for the prevention and treatment of various diseases. The traditional random walk algorithms generally exclude the effect of non-neighboring nodes on random walking. In order to overcome the issue, the neighborhood constraint (NC) approach is proposed in this study for regulating the direction of the random walk by computing the effects of both neighboring nodes and non-neighboring nodes. Then the association matrix is updated by matrix multiplication for minimizing the effect of the false negative data. The heterogeneous lncRNA-disease network is finally analyzed using an unbalanced random walk method for predicting the potential lncRNA-disease associations. The LUNCRW model is therefore developed for predicting potential lncRNA-disease associations. The area under the curve (AUC) values of the LUNCRW model in leave-one-out cross-validation and five-fold cross-validation were 0.951 and 0.9486 ± 0.0011, respectively. Data from published case studies on three diseases, including squamous cell carcinoma, hepatocellular carcinoma, and renal cell carcinoma, confirmed the predictive potential of the LUNCRW model. Altogether, the findings indicated that the performance of the LUNCRW method is superior to that of existing methods in predicting potential lncRNA-disease associations.

Ubiquitin ligase TRIM32 promotes dendrite arborization by mediating degradation of the epigenetic factor CDYL.

Proper dendritic morphology is fundamental to nerve signal transmission; thus, revealing the mechanism by which dendrite arborization is regulated is of great significance. Our previous studies have found that the epigenetic molecule chromodomain Y-like (CDYL) negatively regulates dendritic branching. Current research mostly focuses on the processes downstream of CDYL, whereas the upstream regulatory process has not been investigated to date. In this study, we identified an upstream regulator of CDYL, the E3 ubiquitin ligase tripartite motif-containing protein 32 (TRIM32), which promotes dendrite arborization by mediating the ubiquitylation and degradation of CDYL. By using mass spectrometry and biochemistry strategies, we proved that TRIM32 interacted with CDYL and mediated CDYL ubiquitylation modification in vivo and in vitro. Overexpressing TRIM32 decreased the protein level of CDYL, leading to an increase in the dendritic complexity of primary cultured rat neurons. In contrast, knocking down TRIM32 increased the protein level of CDYL and decreased the dendritic complexity. The truncated form of TRIM32 without E3 ligase activity (ΔRING) lost its ability to regulate dendritic complexity. Most importantly, knockdown of CDYL abolished the reduced complexity of dendrites caused by TRIM32 knockdown, indicating that the TRIM32-mediated regulation of dendritic development depends on its regulation of downstream CDYL. Hence, our findings reveal that TRIM32 could promote dendrite arborization by mediating CDYL degradation. This work initially defines a novel biological role of TRIM32 in regulating mechanisms upstream of CDYL and further presents a potential therapeutic target for the treatment of CDYL-related neurodevelopmental disorders.

Low 15d-PGJ2 status is associated with oxidative stress in chronic obstructive pulmonary disease patients.

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent nuclear receptor and highly expressed in human and rodent lungs. 15-Deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), known for cyclopentenone prostaglandin, is the endogenous ligand of PPARγ. However, the associations among PPARγ, 15d-PGJ2 and chronic obstructive pulmonary disease (COPD) were unclear. METHODS: All 130 fasting blood samples and 40 lung specimens were obtained from COPD patients and control subjects. Serum 15d-PGJ2 was detected by ELISA. The expressions of oxidative stress indicators were measured using western blotting and PPARγ nuclei were evaluated with immunohistochemistry in lungs. The associations among serum 15d-PGJ2, pulmonary PPARγ and oxidative stress indicators, and COPD were estimated. RESULTS: Serum 15d-PGJ2 was reduced in COPD patients compared with healthy volunteers. Linear and logistic regression analysis indicated that serum 15d-PGJ2 was positively associated with pulmonary function in COPD patients. In addition, PPARγ-positive nuclei were reduced and oxidative stress indicators, included HO-1 and NOX-4, were increased in lungs of COPD patients. Further correlative analysis suggested that pulmonary function parameters was positively correlated with serum 15d-PGJ2 and pulmonary PPARγ-positive nuclei, inversely related to oxidative stress indicators in lungs of COPD patients. Pretreatment with 15d-PGJ2 obviously attenuated TNFα-induced oxidative stress in BEAS-2B cells. CONCLUSIONS: Serum 15d-PGJ2 and pulmonary PPARγ are reduced, and oxidative stress is elevated in COPD patients. Serum 15d-PGJ2 is inversely associated with oxidative stress in COPD patients.

Chemical Pretreatments and Anaerobic Digestion Shape the Virome and Functional Microbiome in Fecal Sludge.

The decomposition and pathogen inactivation of fecal sludge (FS) are vitally important for safely managing onsite sanitation and protecting public and environmental health. However, the microbiome and virome assemblages in FS after chemical and biological treatments remain unclear. Here, we reported the differences in the solid reduction and microbiomes of FS subjected to potassium ferrate (PF), alkali (ALK), and sodium hypochlorite (NaClO) pretreatments and anaerobic digestion (AD). The PF and NaClO pretreatments enhanced FS hydrolysis and pathogen suppression, respectively; AD suppressed Gram-positive bacteria. Most of the viromes were those of bacteriophages, which were also shaped by chemical pretreatments and AD. Metatranscriptome analysis revealed distinct gene expression patterns between the PF- and ALK-pretreated FS and the subsequent AD. Differentially expressed gene profiles indicated that genes related to biological processes, molecular functions, and transcriptional regulators were upregulated in ALK-AD and PF-AD samples. These findings suggested that the effect of different treatment technologies on the viral diversity, pathogen abundance, and metabolic function of the core microbiome extends beyond FS decomposition and that the use of combined processes would provide possible alternatives for FS management in pandemic emergencies.

Microbial Niche Differentiation during Nitrite-Dependent Anaerobic Methane Oxidation.

Nitrite-dependent anaerobic methane oxidation (n-DAMO) has been demonstrated to play important roles in the global methane and nitrogen cycle. However, despite diverse n-DAMO bacteria widely detected in environments, little is known about their physiology for microbial niche differentiation. Here, we show the microbial niche differentiation of n-DAMO bacteria through long-term reactor operations combining genome-centered omics and kinetic analysis. With the same inoculum dominated by both species "Candidatus Methylomirabilis oxyfera" and "Candidatus Methylomirabilis sinica", n-DAMO bacterial population was shifted to "Ca. M. oxyfera" in a reactor fed with low-strength nitrite, but shifted to "Ca. M. sinica" with high-strength nitrite. Metatranscriptomic analysis showed that "Ca. M. oxyfera" harbored more complete function in cell chemotaxis, flagellar assembly, and two-component system for better uptake of nitrite, while "Ca. M. sinica" had a more active ion transport and stress response system, and more redundant function in nitrite reduction to mitigate nitrite inhibition. Importantly, the half-saturation constant of nitrite (0.057 mM vs 0.334 mM NO2-) and inhibition thresholds (0.932 mM vs 2.450 mM NO2-) for "Ca. M. oxyfera" vs "Ca. M. sinica", respectively, were highly consistent with genomic results. Integrating these findings demonstrated biochemical characteristics, especially the kinetics of nitrite affinity and inhibition determine niche differentiation of n-DAMO bacteria.

Evidence for Nitrous Oxide Emissions by Nitrite-Dependent Anaerobic Methane Oxidizing Bacteria.

Nitrite-dependent anaerobic methane oxidizing (n-DAMO) bacteria generally convert nitrite to dinitrogen and bypass the nitrous oxide (N2O) formation step. However, N2O is often detected in n-DAMO bacteria dominated cultures and it remains an open question as to the microbial origin of N2O in these enrichments. Using a stable nitrite consuming microbial community enriched for n-DAMO bacteria, we demonstrated that N2O production was coupled to methane oxidation and the higher initial nitrite concentrations led to increased quantities of N2O being formed. Moreover, continuous exposure of the enrichment culture to about 5 mg of N L-1 nitrite resulted in constant N2O being produced (12.5% of nitrite was reduced to N2O). Metatranscriptomic analyses revealed that nitrite reductase (nirS) and nitric oxide reductase (norZ) transcripts from n-DAMO bacteria increased in response to nitrite exposure. No other bacteria significantly expressed nor genes under these conditions, suggesting n-DAMO bacteria are responsible for N2O being produced. In a 35-day bioreactor experiment, N2O produced by the n-DAMO bacteria accumulated when nitrite was in excess; this was found to be up to 3.2% of the nitrogen that resulted from nitrite removal. Together, these results suggested that excess nitrite is an important driver of N2O production by n-DAMO bacteria. To this end, proper monitoring and control of nitrite levels in wastewater treatment plants would be effective strategies for mitigating N2O emissions to the atmosphere.

Revisiting the Engineering Roadmap of Nitrate/Nitrite-Dependent Anaerobic Methane Oxidation.

Nitrate/nitrite-dependent anaerobic oxidation of methane (n-DAMO) is a recently discovered process, which provides a sustainable perspective for simultaneous nitrogen removal and greenhouse gas emission (GHG) mitigation by using methane as an electron donor for denitrification. However, the engineering roadmap of the n-DAMO process is still unclear. This work constitutes a state-of-the-art review on the classical and most recently discovered metabolic mechanisms of the n-DAMO process. The versatile combinations of the n-DAMO process with nitrification, nitritation, and partial nitritation for nitrogen removal are also clearly presented and discussed. Additionally, the recent advances in bioreactor development are systematically reviewed and evaluated comprehensively in terms of methane supply, biomass retention, membrane requirement, startup time, reactor performance, and limitations. The key issues including enrichment and operation strategy for the scaling up of n-DAMO-based processes are also critically addressed. Moreover, the challenges inherent to implementing the n-DAMO process in practical applications, including application scenario recognition, GHG emission mitigation, and operation under realistic conditions, are highlighted. Finally, prospects as well as opportunities for future research are proposed. Overall, this review provides a roadmap for potential applications and further development of the n-DAMO process in the field of wastewater treatment.

Reactivated biofilm coupling n-DAMO with anammox achieved high-rate nitrogen removal in membrane aerated moving bed biofilm reactor.

As a promising technology, the combination of nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) with Anammox offers a solution to achieve effective and sustainable wastewater treatment. However, this sustainable process faces challenges to accumulate sufficient biomass for reaching practical nitrogen removal performance. This study developed an innovative membrane aerated moving bed biofilm reactor (MAMBBR), which supported sufficient methane supply and excellent biofilm attachment, for cultivating biofilms coupling n-DAMO with Anammox. Biofilms were developed rapidly on the polyurethane foam with the supply of ammonium and nitrate, achieving the bioreactor performance of 275 g N m-3 d-1 within 102 days. After the preservation at -20 °C for 8 months, the biofilm was successfully reactivated and achieved 315 g N m-3 d-1 after 188 days. After reactivation, MAMBBR was applied to treat synthetic sidestream wastewater. Up to 99.9% of total nitrogen was removed with the bioreactor performance of 4.0 kg N m-3 d-1. Microbial community analysis and mass balance calculation demonstrated that n-DAMO microorganisms and Anammox bacteria collectively contributed to nitrogen removal in MAMBBR. The MAMBBR developed in this study provides an ideal system of integrating n-DAMO with Anammox for sustainable wastewater treatment.

Widely targeted quantitative lipidomics and prognostic model reveal plasma lipid predictors for nasopharyngeal carcinoma.

BACKGROUND: Dysregulation of lipid metabolism is closely associated with cancer progression. The study aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC), based on lipidomics. METHODS: The plasma lipid profiles of 179 patients with locoregionally advanced NPC (LANPC) were measured and quantified using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set (P < 0.05). A deep survival method called DeepSurv was employed to develop a proposed model based on significant lipid species (P < 0.01) and clinical biomarkers to predict DMFS. Concordance index and receiver operating curve analyses were performed to assess model effectiveness. The study also explored the potential role of lipid alterations in the prognosis of NPC. RESULTS: Forty lipids were recognized as distant metastasis-associated (P < 0.05) by univariate Cox regression. The concordance indices of the proposed model were 0.764 (95% confidence interval (CI), 0.682-0.846) and 0.760 (95% CI, 0.649-0.871) in the training and validation sets, respectively. High-risk patients had poorer 5-year DMFS compared with low-risk patients (Hazard ratio, 26.18; 95% CI, 3.52-194.80; P < 0.0001). Moreover, the six lipids were significantly correlated with immunity- and inflammation-associated biomarkers and were mainly enriched in metabolic pathways. CONCLUSIONS: Widely targeted quantitative lipidomics reveals plasma lipid predictors for LANPC, the prognostic model based on that demonstrated superior performance in predicting metastasis in LANPC patients.

Inadvertent perioperative hypothermia and surgical site infections after liver resection.

BACKGROUND: In the overall surgical population, inadvertent perioperative hypothermia has been associated with an increased incidence of surgical site infection (SSI). However, recent clinical trials did not validate this notion. This study aimed to investigate the potential correlation between inadvertent perioperative hypothermia and SSIs following liver resection. METHODS: This retrospective cohort study included all consecutive patients who underwent liver resection between January 2019 and December 2021 at the First Affiliated Hospital, Zhejiang University School of Medicine. Perioperative temperature managements were implemented for all patients included in the analysis. Estimated propensity score matching (PSM) was performed to reduce the baseline imbalances between the normothermia and hypothermia groups. Before and after PSM, univariate analyses were performed to evaluate the correlation between hypothermia and SSI. Multivariate regression analysis was performed to determine whether hypothermia was an independent risk factor for postoperative transfusion and major complications. Subgroup analyses were performed for diabetes mellitus, age > 65 years, and major liver resection. RESULTS: Among 4000 patients, 2206 had hypothermia (55.2%), of which 150 developed SSI (6.8%). PSM yielded 1434 individuals in each group. After PSM, the hypothermia and normothermia groups demonstrated similar incidence rates of SSI (6.3% vs. 7.0%, P = 0.453), postoperative transfusion (13.3% vs. 13.7%, P = 0.743), and major complications (9.0% vs. 10.1%, P = 0.309). Univariate regression analysis revealed no significant effects of hypothermia on the incidence of SSI in the group with the highest hypothermia exposure [odds ratio (OR) = 1.25, 95% confidence interval (CI): 0.84-1.87, P = 0.266], the group with moderate exposure (OR = 1.00, 95% CI: 0.65-1.53, P = 0.999), or the group with the lowest exposure (OR = 1.11, 95% CI: 0.73-1.65, P = 0.628). The subgroup analysis revealed similar results. Regarding liver function, patients in the hypothermia group demonstrated lower γ-glutamyl transpeptidase (37 vs. 43 U/L, P = 0.001) and alkaline phosphatase (69 vs. 72 U/L, P = 0.016). However, patients in the hypothermia group exhibited prolonged activated partial thromboplastin time (29.2 vs. 28.6 s, P < 0.01). CONCLUSIONS: In our study of patients undergoing liver resection, we found no significant association between mild perioperative hypothermia and SSI. It might be due to the perioperative temperature managements, especially active warming measures, which limited the impact of perioperative hypothermia on the occurrence of SSI.

Biomechanical behavior analysis of four types of short implants with different placement depths using the finite element method.

STATEMENT OF PROBLEM: The clinical application of short implants has been increasing. However, studies on the marginal bone loss of short implants are sparse, and clinicians often choose short implants based on their own experience rather than on scientific information. PURPOSE: The purpose of this finite element analysis study was to evaluate the microstrain-stress distribution in the peri-implant bone and implant components for 4 types of short implants at different placement depths of platform switching. MATERIAL AND METHODS: By using short implants as prototypes, 4 short implant models were 1:1 modeled. The diameter and length of the implants were 5×5, 5×6, 6×5, and 6×6 mm. The restoration was identical for all implants. Three different depths of implant platform switching were set: equicrestal, 0.5-mm subcrestal, and 1-mm subcrestal. The models were then assembled and assigned an occlusal force of 200 N (vertical or 30-degree oblique). A finite element analysis was carried out to evaluate the maximum equivalent elastic strain and von Mises stress in the bone and the stress distribution in the implant components. RESULTS: The 5×5 implant group showed the largest intraosseous strain (21.921×103 µÎµ). A 1-mm increase in implant diameter resulted in a 17.1% to 37.4% reduction in maximum intraosseous strain when loaded with oblique forces. The strain in the bone tended to be much smaller than the placement depth at the equicrestal and 0.5-mm subcrestal positions than that at the 1-mm subcrestal position, especially under oblique force loading, with an increase of approximately 37.4% to 81.8%. In addition, when the cortical bone thickness was less than 4 mm, 5×6 implants caused significantly higher intraosseous stresses than 6×6 implants. CONCLUSIONS: Large implant diameters, rather than long implants, led to reduced intraosseous strain, especially under oblique loading. Regarding the implant platform switching depth, the short implant showed small intraosseous strains when the platform switching depth was equicrestal or 0.5-mm subcrestal.

Relationships among adverse childhood experience patterns, psychological resilience, self-esteem and depressive symptoms in Chinese adolescents: A serial multiple mediation model.

Adverse childhood experiences (ACEs) and adolescent depression are both prevalent social problems that can increase the risk of several negative health consequences throughout life. The original definition of ACEs misdirects the focus of intervention efforts for ACEs to only family dysfunction and parenting practices. We used a broader definition of ACEs and a latent class analysis (LCA) model to examine ACE patterns, aiming to overcome the shortcomings of cumulative and single adversity approaches based on the special social context of China. The data were derived from a middle school in Huaibei City of Anhui Province in 2019 and 2020, which was a prospective study involving 1687 junior high school students. At the initial evaluation (T1), ACEs, psychological resilience, self-esteem, and depressive symptoms were assessed by the students. At Time 2 (T2), the depressive symptoms of students were assessed. LCA and mediation analyses were conducted with Mplus version 8.2. The LCA identified the following three heterogeneous ACE classes: "low adversity" (36.4%), "moderate adversity" (44.2%), and "high adversity" (19.4%). The mediation analysis showed that the ACE patterns affected depressive symptoms through the following two mediation paths only in the moderate but not in the high adversity class: self-esteem alone and a path combining psychological resilience and self-esteem. Psychological resilience separately did not mediate the association between ACE patterns and depressive symptoms. To reduce depressive symptoms, interventions for students with ACEs need to improve self-esteem through many channels.

Deciphering the Inhibition of Ethane on Anaerobic Ammonium Oxidation.

Anaerobic ammonium oxidation (anammox) and nitrification, two common biological ammonium oxidation pathways, are critical for the microbial nitrogen cycle. Short chain alkanes (C2-C8) have been well-known as inhibitors for nitrification through interaction with the ammonia monooxygenase, while whether these alkanes affect anammox is an open question. Here, this work demonstrated significant inhibition of ethane on anammox and revealed the inhibitory mechanism. The acute inhibition of ethane on anammox was concentration-dependent and reversible; 0.86 mM dissolved ethane caused 50% inhibition (IC50), and 1.72 mM ethane almost completely inhibited anammox. After long-term exposure to 0.09 mM ethane for 30 days, the ammonium (nitrite) removal rate dropped from 202 (267) mg N L-1 d-1 to 1 (1) mg N L-1 d-1, and the abundance of anammox bacteria decreased from 61.9% to 9.5%. The intercellular ammonium concentration of anammox bacteria decreased after ethane exposure, while metatranscriptome analysis showed significant upregulation of genes for ammonium transport of anammox bacteria. Thus, ethane could suppress ammonium uptake resulting in the inhibition of anammox activities. As ethane is the second most prevalent alkane after methane in various anoxic environments, ethane may have an important effect on the nitrogen cycle driven by anammox that should be investigated in future research.

Cardiomyocyte peroxisome proliferator-activated receptor α is essential for energy metabolism and extracellular matrix homeostasis during pressure overload-induced cardiac remodeling.

Peroxisome proliferator-activated receptor α (PPARα), a ligand-activated nuclear receptor critical for systemic lipid homeostasis, has been shown closely related to cardiac remodeling. However, the roles of cardiomyocyte PPARα in pressure overload-induced cardiac remodeling remains unclear because of lacking a cardiomyocyte-specific Ppara-deficient (PparaΔCM) mouse model. This study aimed to determine the specific role of cardiomyocyte PPARα in transverse aortic constriction (TAC)-induced cardiac remodeling using an inducible PparaΔCM mouse model. PparaΔCM and Pparafl/fl mice were randomly subjected to sham or TAC for 2 weeks. Cardiomyocyte PPARα deficiency accelerated TAC-induced cardiac hypertrophy and fibrosis. Transcriptome analysis showed that genes related to fatty acid metabolism were dramatically downregulated, but genes critical for glycolysis were markedly upregulated in PparaΔCM hearts. Moreover, the hypertrophy-related genes, including genes involved in extracellular matrix (ECM) remodeling, cell adhesion, and cell migration, were upregulated in hypertrophic PparaΔCM hearts. Western blot analyses demonstrated an increased HIF1α protein level in hypertrophic PparaΔCM hearts. PET/CT analyses showed an enhanced glucose uptake in hypertrophic PparaΔCM hearts. Bioenergetic analyses further revealed that both basal and maximal oxygen consumption rates and ATP production were significantly increased in hypertrophic Pparafl/fl hearts; however, these increases were markedly blunted in PparaΔCM hearts. In contrast, hypertrophic PparaΔCM hearts exhibited enhanced extracellular acidification rate (ECAR) capacity, as reflected by increased basal ECAR and glycolysis but decreased glycolytic reserve. These results suggest that cardiomyocyte PPARα is crucial for the homeostasis of both energy metabolism and ECM during TAC-induced cardiac remodeling, thus providing new insights into potential therapeutics of cardiac remodeling-related diseases.