Genome analysis of Salinimicrobium sp. 3283s, a deep-sea bacterium isolated from the sediments of South China Sea, China.

Salinimicrobium sp. 3283s is an aerobic, golden-yellow pigment-producing, Flavobacteriaceae bacterium isolated from the sediments at the depth of 1751 m in the South China Sea. In this study, we present the complete genome sequence of strain 3283s, which only have a single circular chromosome comprising 3,702,683 bp with 41.41% G + C content and no circular plasmid. In total, 3257 protein coding genes, 45 tRNA, 9 rRNA, and 13 sRNA genes were obtained. In terms of the function of gene annotation, strain 3283s was more different from Salinimicrobium oceani J15B91, which was isolated from the South China Sea at a similar depth, and more similar to a Mariana Trench-derived strain Salinimicrobium profundisediminis MT39, which was closer in phylogenetic taxonomic status, suggesting that strain 3283s possesses a stronger potential to adapt to the deep-sea environment. Furthermore, the high- pressure simulations also confirmed that strain 3283s can grow in both 30 MPa and 60 MPa hydrostatic pressure environments, and that it grows better in 30 MPa hydrostatic pressure environments than in 60 MPa hydrostatic pressure environments. In addition, we found a large number of genes in strain 3283s that can promote better adaptation of the bacteria to the low oxygen and high hydrostatic pressure (HHP) environment of the deep sea, such as biosynthetic enzymes of antioxidant pigments, genes encoding cytochromes with enhanced affinity for oxygen, proteins for adaptation to HHP, and genes encoding TonB-dependent transporters in the absence of flagella.

α-Pyrone mediates quorum sensing through the conservon system in Nocardiopsis sp.

Actinobacteria produce a plethora of bioactive secondary metabolites that are often regulated by quorum-sensing signaling molecules via specific binding to their cognate TetR-type receptors. Here, we identified monocyclic α-pyrone as a new class of actinobacterial signaling molecules influencing quorum sensing process in Nocardiopsis sp. LDBS0036, primarily evidenced by a significant reduction in the production of phenazines in the pyrone-null mutant compared to the wild-type strain. Exogenous addition of the α-pyrone can partially restore the expression of some pathways to the wild strain level. Moreover, a unique multicomponent system referred to as a conservon, which is widespread in actinobacteria and generally contains four or five functionally conserved proteins, may play an important role in detecting and transmitting α-pyrone signals in LDBS0036. We found the biosynthetic gene clusters of α-pyrone and their associated conservon genes are highly conserved in Nocardiopsis, indicating the widespread prevalence and significant function of this regulate mechanism within Nocardiopsis genus. Furthermore, homologous α-pyrones from different actinobacterial species were also found to mediate interspecies communication. Our results thus provide insights into a novel quorum-sensing signaling system and imply that various modes of bacterial communication remain undiscovered.

Relationship between autoimmune thyroid antibodies and anti-nuclear antibodies in general patients.

Background: There is no doubt that both Hashimoto thyroiditis and Graves' disease are autoimmune thyroid diseases (AITDs), but the relationship between anti-nuclear antibody (ANA) and AITDs is poorly studied. The association between thyroid autoantibody levels and ANA positivity was evaluated to assess the role of ANA in AITDs. Methods: We conducted an analysis using data from 1,149,893 patients registered at our hospital and 53,021 patients registered in the National Health and Nutrition Examination Survey databases. We focused on patients with data for thyroid peroxidase antibody (TPOAb)/ANA, TPOAb/immunoglobulin G (IgG), thyroid-stimulating hormone (TSH) receptor antibody (TRAb)/ANA, TRAb/IgG, TSH/ANA, or TSH/IgG. Results: ANA positivity rates were 12.88% and 21.22% in TPOAb/ANA and TSH/ANA patients, respectively. In TPOAb/IgG and TSH/IgG data, high IgG levels (≥15 g/L) were detected in 2.23% and 4.06% of patients, respectively. There were significant differences in ANA positivity rates and high IgG proportions among patients with different TPOAb and TSH levels. TPOAb level was correlated with ANA positivity rate and high IgG proportion, and TSH level was correlated with ANA positivity rate. Regression analysis showed positive correlations between TPOAb levels and ANA positivity risk or high IgG risk, TSH levels and high IgG risk, and elevated TSH and ANA positivity risk. Of patients with TRAb/ANA data, 35.99% were ANA-positive, and 13.93% had TRAb levels ≥1.75IU/L; 18.96% of patients with TRAb/IgG data had high IgG levels, and 16.51% had TRAb levels ≥1.75IU/L. ANA positivity rate and high IgG proportion were not significantly different among different TRAb levels. TRAb levels, ANA positivity risk and high IgG risk were not correlated. Conclusion: ANA positivity and high IgG are related to Hashimoto thyroiditis but not Graves' disease, which implies distinct pathophysiological mechanisms underlying the AITDs.

Effects of time-restricted eating on intrahepatic fat and metabolic health among patients with nonalcoholic fatty liver disease.

OBJECTIVE: The study's objective was to explore whether early time-restricted eating (eTRE) and late time-restricted eating (lTRE) have different impacts on intrahepatic fat and metabolic health among patients with nonalcoholic fatty liver disease (NAFLD). METHODS: This is an 8-week, randomized, parallel-arm, open-label trial. Forty eligible patients were randomly assigned to eTRE (eating between 8:00 a.m. and 4:00 p.m.) or lTRE (eating between 12:00 p.m. and 8:00 p.m.). The primary outcome was the change of intrahepatic fat measured by magnetic resonance image-derived proton density fat fraction. Secondary outcomes included changes in weight, body composition, liver function, and cardiometabolic factors. RESULTS: Forty participants who underwent randomization completed the trial (mean age: 38.25 years). The eTRE group had a -3.24% absolute reduction of intrahepatic fat (95% CI: -4.55% to -1.92%) and there was a -3.51% absolute reduction for the lTRE group (95% CI: -5.10% to -1.92%). Changes in intrahepatic fat were not statistically different between the two groups. Both the eTRE and lTRE groups had similar and significant reductions in weight, visceral fat, subcutaneous fat, liver enzymes, and glucose regulatory indicators. CONCLUSIONS: Among patients with NAFLD, both eTRE and lTRE induced significant reductions in intrahepatic fat and improvements in body composition, liver function, and metabolic health with similar magnitude. These findings suggest that eTRE and lTRE are comparable and feasible strategies for NAFLD management.

Chemical constituents of Wikstroemia alternifolia and their neuroprotective activities.

Phytochemical investigation on the plant of Wikstroemia alternifolia led to the isolation of 26 compounds including two new ones, wikstralternifols A and B (1 and 7). Their structures including the absolute configuration were elucidated by spectroscopic data together with analysis of experimental and calculated ECD data. All compounds were isolated from this plant for the first time, and their main structural types were lignans, sesquiterpenoids, and flavonoids. In the sodium nitroprusside-induced rat pheochromocytoma PC-12 cell model, the neuroprotective activities of the selected sesquiterpenoids (1 and 4) and lignans (7 - 14) were screened at the concentration of 10 µM, and 7 - 14 displayed better activities than the positive control edaravone.

Triple combination of HAIC-FO plus tyrosine kinase inhibitors and immune checkpoint inhibitors for advanced hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: The triple combination of hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitors (ICIs) is expected to have a synergistic anticancer effect in HCC. We conducted this meta-analysis to evaluate the efficacy and safety of the triple combination treatment in advanced HCC patients. METHODS: PubMed, Embase, Cochrane Library, Web of Science databases were systematically searched for relevant studies from the inception of each database to May 10, 2023. All articles focusing the triple combination treatment of HAIC-FO plus TKI and ICIs for advanced HCC were eligible. The meta-analysis was conducted following the PRISMA guidelines. The risk of bias was assessed using the Joanna Briggs Institute (JBI) for case series and Newcastle-Ottawa Scale (NOS) for cohort studies. The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). The secondary results were adverse events. Further meta-analysis of control studies demonstrated the superiority of the triple combination modality to TKI plus ICIs, and TKI alone. RESULTS: Nine articles (four cohort studies and five one-arm studies) involving 777 advanced HCC patients were included in this meta-analysis. In terms of survival analysis, the pooled median PFS was 11 months (95% CI: 10.1-12.0 months) with low heterogeneity (I2 = 0%, p = 0.97). With regard to tumor response, the pooled ORR and DCR was 61.6% (I2=0%, p = 0.71) and 87.9% (I2 = 13%, p = 0.33) with low heterogeneity, respectively. As compared with TKIs plus ICIs, and TKIs alone, the triple combination thrapy was associated with improved median OS (HR=0.51, 95%CI 0.41-0.62) with low heterogeneity across studies (I2 = 0%, p = 0.47), median PFS (HR=0.51, 95%CI 0.41-0.64) with low heterogeneity across studies (I2 = 0%, p = 0.41), ORR (RR = 0.56, 95% CI: 0.42-0.74) with high heterogeneity across studies (I2 = 69%, p = 0.02), and DCR (RR = 0.38, 95%CI 0.27-0.54) with low heterogeneity across studies (I2 = 14%, p = 0.32). The most common 3/4 AEs were elevated ALT and AST, thrombocytopenia, hypertension, nausea and vomiting in this meta-analysis. CONCLUSIONS: The triple combination therapy of HAIC-FO plus TKI and ICIs showed promising efficacy and safety in patients with advanced HCC. REGISTRATION: The protocol was registered with PROSPERO (ID:CRD42023424281).

Can accelerated ageing models inform us on age-related tauopathies?

Ageing is the greatest risk factor of late-onset neurodegenerative diseases. In the realm of sporadic tauopathies, modelling the process of biological ageing in experimental animals forms the foundation of searching for the molecular origin of pathogenic tau and developing potential therapeutic interventions. Although prior research into transgenic tau models offers valuable lessons for studying how tau mutations and overexpression can drive tau pathologies, the underlying mechanisms by which ageing leads to abnormal tau accumulation remains poorly understood. Mutations associated with human progeroid syndromes have been proposed to be able to mimic an aged environment in animal models. Here, we summarise recent attempts in modelling ageing in relation to tauopathies using animal models that carry mutations associated with human progeroid syndromes, or genetic elements unrelated to human progeroid syndromes, or have exceptional natural lifespans, or a remarkable resistance to ageing-related disorders.

Discovering a New Okadaic Acid Derivative, a Potent HIV Latency Reversing Agent from Prorocentrum lima PL11: Isolation, Structural Modification, and Mechanistic Study.

Marine toxins (MTs) are a group of structurally complex natural products with unique toxicological and pharmacological activities. In the present study, two common shellfish toxins, okadaic acid (OA) (1) and OA methyl ester (2), were isolated from the cultured microalgae strain Prorocentrum lima PL11. OA can significantly activate the latent HIV but has severe toxicity. To obtain more tolerable and potent latency reversing agents (LRAs), we conducted the structural modification of OA by esterification, yielding one known compound (3) and four new derivatives (4-7). Flow cytometry-based HIV latency reversal activity screening showed that compound 7 possessed a stronger activity (EC50 = 46 ± 13.5 nM) but was less cytotoxic than OA. The preliminary structure-activity relationships (SARs) indicated that the carboxyl group in OA was essential for activity, while the esterification of carboxyl or free hydroxyls were beneficial for reducing cytotoxicity. A mechanistic study revealed that compound 7 promotes the dissociation of P-TEFb from the 7SK snRNP complex to reactivate latent HIV-1. Our study provides significant clues for OA-based HIV LRA discovery.

Prenylated dihydroflavones from the root barks of Morus alba.

Three new prenylated dihydroflavones, moralbaflavones A-C (1-3), together with four known ones (4a/4b, 5, and 6) were isolated from the root barks of Morus alba L. Their structures including the absolute configurations were determined by the analysis of HRMS, NMR, and ECD data. The neuroprotective properties of these prenylated dihydroflavones were screened at the concentration of 10 µM in the sodium nitroprusside-induced rat pheochromocytoma PC-12 cells, and the results showed moralbaflavone C (3) possessed significant neuroprotective activity, being more potent than the positive control edaravone.

Elevated Intracranial Pressure After Primary Surgical Correction of Sagittal Suture Craniosynostosis.

Study Design: A Case Report. Objective: Craniosynostosis is a craniofacial condition defined by premature fusion of at least one cranial suture. Resynostosis or secondary craniosynostosis of a previously patent adjacent suture following primary repair is a relatively common complication. While studies have assessed the rates of secondary craniosynostosis and subsequent reoperation, extremely limited data regarding reoperation techniques is available. Methods: We present a unique case of a pediatric patient with sagittal craniosynostosis who previously underwent a modified pi procedure and later developed resynostosis of the sagittal suture and secondary synostosis of the bicoronal sutures. We subsequently performed total cranial vault reconstruction with virtual surgical planning (VSP). Results: At his 31-month postoperative follow-up, he displayed normal head shape and denied any clinical signs of elevated intracranial pressures with a normal ophthalmological exam. Conclusions: The reoperation was successful with no significant postoperative complications noted. Performing geometric expansion with VSP to manage fusion of a previously open suture following primary treatment of sagittal synostosis should be considered within the armamentarium of operative options.

Diversity of sesquiterpenoids from Stellera chamaejasme with neuroprotective effects.

Chromatographic fractionation of the 95% EtOH extract of the roots of Stellera chamaejasme yielded 20 sesquiterpenoids of four different types, guaiane-, carotane-, sesquicarane-, and alpiniane-types. Among them, sesquistrachanoids A-F were previously undescribed ones, whose structures including absolute configurations were elucidated by spectroscopic methods, the Mo2(OAc)4-induced ECD experiment, and analysis of experimental and calculated 1D NMR and ECD data. Sesquistrachanoid A is a 2,3-seco-guaiane-type sesquiterpenoid with a α-pyrone core and sesquistrachanoid B is the first example of 8,9-seco-guaiane-type sesquiterpenoid featured with an 1,8-δ-lactone core. Sesquistrachanoid C is a guaiane sesquiterpenoid characterized by a peroxide bridge between C-8 and C-10. All sesquiterpenoids were evaluated for their neuroprotective effects on cell damage induced by sodium nitroprusside in PC-12 cells. The bioassay results showed that six compounds at 10 µM could restore the cell viability, being comparable to that of the positive control edaravone. The mechanistic study on the most pronounced activity compound, stelleraguaianone B, demonstrated that it played a neuroprotective role by promoting the mRNA expression of antioxidant enzymes to reduce oxidative stress.

Nonlinear dynamics of membrane skeleton in osteocyte.

Osteocytes play an important role in mechanosensation and conduction in bone tissue, and the change of mechanical environment can affect the sensitivity of osteocytes to external stimulation. The structure of osteocytes will be changed when they are subjected to vibrations, which influence the mechanosensitivity of osteocytes and alter the regulation of bone remodeling process. As an important mechanotransduction structure in osteocytes, the membrane skeleton greatly affects the mechanosensation and conduction of osteocytes. However, the dynamic responses of membrane skeleton to the vibration and the structural changes of membrane skeleton are unclear. Therefore, we applied a nonlinear dynamics method to explain the time-dependent changes of membrane skeleton. The semi-ellipsoidal reticulate shell structure of membrane skeleton is built based on the experimental observation in our previous work. Then, the nonlinear dynamic equations of membrane skeleton are established according to the theory of plate and shell dynamics, and the displacement-time curves, phase portraits, and Poincaré maps of membrane skeleton structure were obtained. The numeration results show that under the vibration stimulation of 15 Hz, 30 Hz, 60 Hz, and 90 Hz, the membrane skeleton is destroyed after a transient equilibrium position vibration. The vibration of 15 Hz has the most destructive effect on the membrane skeleton, the natural frequency of membrane skeleton may be less than 15 Hz. In addition, the chaos phenomenon occurs to the membrane skeleton during vibration. As a damping factor, the existence of viscosity alleviates the damage of structure. This study can help us to understand the oscillation characteristic of membrane skeleton in osteocyte.

Prion-like strain effects in tauopathies.

Tau is a microtubule-associated protein that plays crucial roles in physiology and pathophysiology. In the realm of dementia, tau protein misfolding is associated with a wide spectrum of clinicopathologically diverse neurodegenerative diseases, collectively known as tauopathies. As proposed by the tau strain hypothesis, the intrinsic heterogeneity of tauopathies may be explained by the existence of structurally distinct tau conformers, "strains". Tau strains can differ in their associated clinical features, neuropathological profiles, and biochemical signatures. Although prior research into infectious prion proteins offers valuable lessons for studying how a protein-only pathogen can encompass strain diversity, the underlying mechanism by which tau subtypes are generated remains poorly understood. Here we summarize recent advances in understanding different tau conformers through in vivo and in vitro experimental paradigms, and the implications of heterogeneity of pathological tau species for drug development.

Complete genome sequence of piezotolerant Stutzerimonas kunmingensis 7850S isolated from the sediment of the Mariana Trench.

Stutzerimonas kunmingensis 7850S is a piezotolerant bacterium isolated from the sediment of the Mariana trench. Here, we described the complete genome of strain 7850S, which contains a single circular chromosome of 4,775,870 base pairs with 62.66% G + C content, and harbors 4494 protein-coding genes, 65 transfer RNA genes, and 12 ribosomal RNA genes. The experimental results showed that strain 7850S could grow under hydrostatic pressure of 0.1-70 MPa. Genomic analyses led to identifications of numbers of high hydrostatic pressure-associated genes, such as the ones associated with unsaturated fatty acids, betaine, and ectoine. A complete set of denitrification genes and some heavy metal detoxification genes were also found in this strain. The presence of these genes suggests metabolic characteristics for adaption to hadal environments and provides insights to further understand adaption strategies and ecological roles of Stutzerimonas in hadal environments.

Microbial diversity and biogeochemical cycling potential in deep-sea sediments associated with seamount, trench, and cold seep ecosystems.

Due to their extreme water depths and unique physicochemical conditions, deep-sea ecosystems develop uncommon microbial communities, which play a vital role in biogeochemical cycling. However, the differences in the compositions and functions of the microbial communities among these different geographic structures, such as seamounts (SM), marine trenches (MT), and cold seeps (CS), are still not fully understood. In the present study, sediments were collected from SM, MT, and CS in the Southwest Pacific Ocean, and the compositions and functions of the microbial communities were investigated by using amplicon sequencing combined with in-depth metagenomics. The results revealed that significantly higher richness levels and diversities of the microbial communities were found in SM sediments, followed by CS, and the lowest richness levels and diversities were found in MT sediments. Acinetobacter was dominant in the CS sediments and was replaced by Halomonas and Pseudomonas in the SM and MT sediments. We demonstrated that the microbes in deep-sea sediments were diverse and were functionally different (e.g., carbon, nitrogen, and sulfur cycling) from each other in the seamount, trench, and cold seep ecosystems. These results improved our understanding of the compositions, diversities and functions of microbial communities in the deep-sea environment.

Activity enhancement of a photo-generated carrier in CsPbBr3 nanocrystals improved by Cd element.

Doping Cd element into perovskite materials is an effective strategy to improve the photoelectric property. However, the further discussion for carrier dynamic behavior in perovskites affected by Cd element remains not sufficient. In this research letter, based on steady and transient spectroscopy, it is found that adding Cd element into CsPbBr3 nanocrystals can enhance the activity of photo-generated carriers and accompany with the optimization of crystal structure. The former improves the carrier heating effect, which makes carrier keep high temperature for a long time and accelerate the bimolecular and the Auger recombination simultaneously. The latter can restrict the monomolecular recombination through passivating the defect states. Finally, they together improve the photoluminescence characteristics of the Cd doped CsPbBr3 nanocrystals and make them exhibit a huge potential in the fields of optoelectronics or photo-catalysis.

Composition and Ecological Roles of the Core Microbiome along the Abyssal-Hadal Transition Zone Sediments of the Mariana Trench.

The unique geological features of hadal trenches are known to influence both the structure and ecological function of microbial communities. It is also well known that heterotrophs and chemoautotrophs dominate the hadal and abyssal pelagic zones, respectively. Here, a metagenomic investigation was conducted on sediment samples obtained from the abyssal-hadal transition zone in the Mariana Trench to gain a better understanding of the general diversity and potential function of the core microbiome in this zone. A high level of cosmopolitanism existed in the core microbiome referred from a high community similarity among different stations. Niche differentiation along the fine-scale of different sediment layers was observed, especially for major archaeal groups, largely due to sediment depth and the source of organic matter. A prevalence of nitrogen biogeochemical cycles driven by various nitrifying groups with the capability of dark carbon fixation in the abyssal-hadal biosphere was also demonstrated. The predominance of heterotrophic over chemolithoautotrophic pathways in this transition zone was found, and a high abundance of genes related to respiration and carbon fixation (i.e., the intact Calvin and rTCA cycles) were detected as well, which might reflect the intensive microbial activities known to occur in this deep biosphere. The presence of those metabolic processes and associated microbes were reflected by functional and genetic markers generated from the metagenomic data in the current study. However, their roles and contributions to the nitrogen/carbon biogeochemical cycles and flux in the abyssal-hadal transition zone still need further analysis. IMPORTANCE The Mariana Trench is the deepest oceanic region on earth, its microbial ecological exploration has become feasible with the rapid progress of submersible and metagenomic sequencing. We investigated the community compositions and metabolic functions of the core microbiome along the abyssal-hadal transition zone of the Mariana Trench, although most studies by far were focused on the pelagic zone. We found a predominance of heterotrophic groups and related metabolic pathways, which were closely associated with nitrogen biogeochemical cycles driven by various nitrifying groups with the capability of dark carbon fixation.

Homo/Hetero-Dimers of Aromatic Bisabolane Sesquiterpenoids with Neuroprotective Activity from the Fungus Aspergillus versicolor A18 from South China Sea

Chromatographic fractionation of the EtOH extracts of the marine-derived fungus Aspergillus versicolor A18 has led to the isolation of 11 homo/hetero-dimers of aromatic bisabolane sesquiterpenoids including eight diphenyl ether-coupled aromatic bisabolanes (1a/1b and 5−10) and three homodimers (2−4), together with their monomers including three aromatic bisabolanes (11−13) and two diphenyl ethers (14 and 15). Their structures and absolute configurations were elucidated by extensive spectroscopic analysis including HRESIMS, 1D/2D NMR, calculated ECD, and the optical rotatory data. Among the four new compounds, (+/−)-asperbisabol A (1a/1b), asperbisabol B (2), and asperbisabol C (3), the enantiomers 1a and 1b represent an unprecedented skeleton of diphenyl ether-coupled aromatic bisabolane sesquiterpenoids with a spiroketal core moiety. The neuroprotective effects of selected compounds against sodium nitroprusside (SNP)-induced injury were evaluated in PC12 cells by the MTT assay. Five compounds (1a, 6, and 8−10) showed remarkable neuroprotective activities at 10 µM, being more active than the positive control edaravone.

Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer's disease.

Although genetic factors play a main role in determining the risk of developing Alzheimer's disease (AD), they do not explain extensive spectrum of clinicopathological phenotypes. Deposits of aggregated TAU proteins are one of the main predictors of cognitive decline in AD. We investigated the hypothesis that variabilities in AD progression could be due to diverse structural assemblies (strains) of TAU protein. Using sensitive biophysical methods in 40 patients with AD and markedly different disease durations, we identified populations of distinct TAU particles that differed in size, structural organization, and replication rate in vitro and in cell assay. The rapidly replicating, distinctly misfolded TAU conformers found in rapidly progressive AD were composed of ~80% misfolded four-repeat (4R) TAU and ~20% of misfolded 3R TAU isoform with the same conformational signatures. These biophysical observations suggest that distinctly misfolded population of 4R TAU conformers drive the rapid decline in AD and imply that effective therapeutic strategies might need to consider not a singular species but a cloud of differently misfolded TAU conformers.