Multi-domain interaction mediated strength-building in human α-actinin dimers unveiled by direct single-molecule quantification.

α-Actinins play crucial roles in cytoskeletal mechanobiology by acting as force-bearing structural modules that orchestrate and sustain the cytoskeletal framework, serving as pivotal hubs for diverse mechanosensing proteins. The mechanical stability of α-actinin dimer, a determinant of its functional state, remains largely unexplored. Here, we directly quantify the force-dependent lifetimes of homo- and hetero-dimers of human α-actinins, revealing an ultra-high mechanical stability of the dimers associated with > 100 seconds lifetime within 40 pN forces under shear-stretching geometry. Intriguingly, we uncover that the strong dimer stability is arisen from much weaker sub-domain pair interactions, suggesting the existence of distinct dimerized functional states of the dimer, spanning a spectrum of mechanical stability, with the spectrin repeats (SRs) in folded or unfolded conformation. In essence, our study supports a potent mechanism for building strength in biomolecular dimers through weak, multiple sub-domain interactions, and illuminates multifaceted roles of α-actinin dimers in cytoskeletal mechanics and mechanotransduction.

The second cutaneous anthrax infection diagnosed by metagenomic next-generation sequencing: A case report.

RATIONALE: Anthrax is a severe zoonotic infectious disease caused by Bacillus anthracis. Most reported cases were traditionally diagnosed through culture and microscopy. We reported here the second case of cutaneous anthrax diagnosed by metagenomic next-generation sequencing (mNGS). PATIENT CONCERNS: A 63-year-old man had a history of contact with an unwell sheep, developing local redness and swelling on wrist. The dorsal side of the left hand and forearm, with tension blisters on the back of the left. DIAGNOSIS: B anthracis was detected from culturing and mNGS of tension blisters. INTERVENTIONS: On the second day of admission, the patient was administered 3.2 million units of penicillin every 6 hours, and isolated and closely observed. OUTCOMES: The patient improves and is discharged. LESSONS: Traditional bacterial cultures are time-consuming, while mNGS offers the advantage of accurate, quick, high-throughput, unbiased sequencing of all genetic material in a sample, which is a good technical tool for assisting in the diagnosis of rare pathogen infections.

Rare occurrence of pulmonary coinfection involving Aspergillus fumigatus and Nocardia cyriacigeorgica in immunocompetent patients based on NGS: A case report and literature review.

RATIONALE: In our search on PubMed, we found that reports of co-infections involving Aspergillus fumigatus and Nocardia cyriacigeorgica in the literature are notably scarce. Most cases have been documented in patients with compromised immune systems or underlying pulmonary conditions. In contrast, our patient did not present with any of these risk factors. Furthermore, there have been no recent incidents such as near-drowning or other accidents in the patient history. To the best of our knowledge, this case represents a hitherto unreported clinical scenario. To enhance comprehension, we conducted a comprehensive literature review by compiling a total of 20 case reports (spanning from 1984 to 2023) on co-infections involving Aspergillus and Nocardia species, retrieved from PubMed. PATIENT CONCERNS AND DIAGNOSIS: Chest CT revealed the presence of multiple nodules and clustered high-density shadows in both lungs. Bronchoscopy revealed mucosal congestion and edema in the apical segment of the right upper lobe of the lung, along with the presence of 2 spherical polypoid new organisms. The pathological analysis reported severe chronic inflammation with evidence of Aspergillus within the tissue. Next-Generation Sequencing of bronchoalveolar lavage fluid revealed the presence of reads corresponding to A fumigatus and N cyriacigeorgica. Positive cultures for A fumigatus and the Nocardia genus were yielded by prolonging the incubation of samples in the microbiology laboratory. INTERVENTIONS: Treatment with voriconazole for A fumigatus and sulfamethoxazole-trimethoprim for N cyriacigeorgica infection was given. OUTCOMES: The patient improved and was discharged. After 6 months of telephone follow-up, the patient reported no clinical symptoms, discontinued the medication on his own. LESSONS: A fumigatus and N cyriacigeorgica can manifest as a co-infection in immunocompetent patients. Clinicians should prioritize the significant advantages and value of NGS in detecting rare and mixed pathogens associated with pulmonary infections.

Protective Effects of Dexmedetomidine on the Vascular Endothelial Barrier Function by Inhibiting Mitochondrial Fission via ER/Mitochondria Contact.

The damage of vascular endothelial barrier function induced by sepsis is critical in causing multiple organ dysfunctions. Previous studies showed that dexmedetomidine (Dex) played a vital role in protecting organ functions. However, whether Dex participates in protecting vascular leakage of sepsis and the associated underlying mechanism remains unknown yet. We used cecal ligation and puncture induced septic rats and lipopolysaccharide stimulated vascular endothelial cells (VECs) to establish models in vivo and in vitro, then the protective effects of Dex on the vascular endothelial barrier function of sepsis were observed, meanwhile, related mechanisms on regulating mitochondrial fission were further studied. The results showed that Dex could significantly reduce the permeability of pulmonary veins and mesenteric vessels, increase the expression of intercellular junction proteins, enhance the transendothelial electrical resistance and decrease the transmittance of VECs, accordingly protected organ functions and prolonged survival time in septic rats. Besides, the mitochondria of VECs were excessive division after sepsis, while Dex could significantly inhibit the mitochondrial fission and protect mitochondrial function by restoring mitochondrial morphology of VECs. Furthermore, the results showed that ER-MITO contact sites of VECs were notably increased after sepsis. Nevertheless, Dex reduced ER-MITO contact sites by regulating the polymerization of actin via α2 receptors. The results also found that Dex could induce the phosphorylation of the dynamin-related protein 1 through down-regulating extracellular signal-regulated kinase1/2, thus playing a role in the regulation of mitochondrial division. In conclusion, Dex has a protective effect on the vascular endothelial barrier function of septic rats. The mechanism is mainly related to the regulation of Drp1 phosphorylation of VECs, inhibition of mitochondrial division by ER-MITO contacts, and protection of mitochondrial function.

Genetic Properties of a Nested Association Mapping Population Constructed With Semi-Winter and Spring Oilseed Rapes.

Nested association mapping (NAM) populations have been widely applied to dissect the genetic basis of complex quantitative traits in a variety of crops. In this study, we developed a Brassica napus NAM (BN-NAM) population consisting of 15 recombination inbred line (RIL) families with 2,425 immortal genotypes. Fifteen high-density genetic linkage maps were constructed by genotyping by sequencing (GBS) based on all RIL families, with further integration into a joint linkage map (JLM) having 30,209 unique markers in common with multiple linkage maps. Furthermore, an ultra-density whole-genome variation map was constructed by projecting 4,444,309 high-quality variants onto the JLM. The NAM population captured a total of 88,542 recombination events (REs). The uneven distribution of recombination rate along chromosomes is positively correlated with the densities of genes and markers, but negatively correlated with the density of transposable elements and linkage disequilibrium (LD). Analyses of population structure and principal components revealed that the BN-NAM population could be divided into three groups with weak stratification. The LD decay distance across genome varied between 170 and 2,400 Kb, with LD decay more rapid in the A than in the C sub-genome. The pericentromeric regions contained large LD blocks, especially in the C sub-genome. This NAM population provides a valuable resource for dissecting the genetic basis of important traits in rapeseed, especially in semi-winter oilseed rape.

[Indexes of forensic identification by the digital orthopantomogram of the normal teeth].

OBJECTIVE: To explore more concise and unified forensic identification indexes for people with none dental disease in digital orthopantomogram. METHODS: To select randomly 170 digital orthopantomogram with none dental disease. Then to select indexes for full dentition patterns and dental alignment patterns according to the dental physiological variations and the characters of dental alignment respectively. Finally diversity of the indexes would be evaluated by statistical analysis. RESULTS: The group with none dental disease had 74 kinds of full dentition pattern in 170 samples, thus its diversity was 43.53%. The group had 129 kinds of dental alignment pattern, thus its diversity was 75.88%. The group had 150 kinds of full dentition/dental alignment pattern, thus its diversity was 88.24%. CONCLUSION: The diversity of the full dentition pattern was not very good. So the full dentition coding was not very effective when it was used solely. The diversity of dental alignment pattern was good. So the method of dental alignment coding could be used in the maxillofacial forensic identification. If the group was coded by the full dentition and dental alignment pattern at the same time, its diversity was better than any single pattern. So the method would be valuable in forensic identification.