Feasibility of circular fermentation as a new strategy to accelerate fermentation and enhance flavor of Antarctic krill paste.

A recycled fermented shrimp paste made by adding old shrimp paste (Antarctic krill paste that has been fermented for 28 T in a room temperature location) and fermenting it again for 28 days. To investigate the changes in their physicochemical indices: water content, volatile salt base nitrogen, malondialdehyde content, protein content and total colony count during fermentation. The flavour substances of shrimp paste samples at the 28 T were investigated by GC-IMS, and the results showed that 31 volatile components were determined. Aldehydes isoamyl alcohol and dimethyl sulphide contributed more to the flavour of Antarctic krill paste. The microbial dynamics during fermentation were detected using high-throughput sequencing. It was found that the rate of dominant flora formation accelerated with the addition of more old shrimp paste. The higher the salinity was, the higher was the species richness. The dominant bacteria genera were more diversified.

NIR Laser Irradiation Promotes Osteogenic Differentiation of PDLSCs Through the Activation of TRPV1 Channels and Subsequent Calcium Signaling.

Near-infrared (NIR) irradiation has shown potential to stimulate osteogenic differentiation, but the mechanisms are not fully understood. The study is to investigate the effects of NIR laser irradiation on osteoblastic differentiation. Human periodontal ligament stem cells (hPDLSCs) were cultured in osteogenic medium and exposed to 810 nm NIR laser at 0.5 J/cm2 every 48 h. The transient receptor potential vanilloid (TRPV1) channel inhibitor capsazepine (CPZ) was used to evaluate the role of calcium influx. Osteogenic differentiation was assessed by proliferation (CCK-8), alkaline phosphatase (ALP) activity, mineralization (Alizarin Red), and expression of bone markers by PCR and Western blot over 2 weeks. Intracellular calcium was measured by Fluo-4M dye and flow cytometry. Results showed that NIR irradiation enhanced hPDLSC proliferation, ALP activity, mineralization, and bone marker expression, indicating increased osteogenic differentiation. These effects were inhibited by CPZ. NIR induced a transient rise in intracellular calcium peaking at 3 min, which was blocked by CPZ. In conclusion, this study demonstrates that NIR laser irradiation promotes osteogenic differentiation of PDLSCs through the activation of TRPV1 channels and subsequent calcium signaling. Further research is warranted to optimize the treatment parameters and elucidate the detailed signaling pathways involved, paving the way for the clinical application of NIR therapy in the treatment of bone disorders and periodontal disease.

Self-Assembled PEGylated Nanocubes Based on Hydrophobic Camptothecin and Doxorubicin for Combinational Therapy of Colorectal Cancer.

Nanoassemblies based on drug conjugates with high drug loading efficiency and stability have been regarded as promising candidates for the next generation of drug formulations. However, they are mostly amphiphilic. Here, a dual-hydrophobic drug conjugate-based nanoassembly has been created for enhanced synergistic antiproliferation against colorectal cancer cells. Camptothecin (CPT) and doxorubicin (DOX) were chosen as the hydrophobic drugs and covalently linked with a disulfide bond (-ss-). The synthesized CPT-ss-DOX can self-assemble into nanocubes (NCs) in an aqueous solution with the assistance of a small amount of polyethylene glycol (PEG), named PEGylated CPT-ss-DOX NCs. The PEGylated CPT-ss-DOX NCs were approximately 111.8 nm, possessing a crystal structure and a very low critical aggregation concentration (8.36 µg·mL-1). The self-assembly mechanism was studied using molecular docking and molecular dynamic simulation methods. The NCs demonstrated excellent storage stability and improved water solubility of CPT and DOX. These NCs could be taken up by cancer cells and gradually release the drugs. In addition, they had higher toxicity to cancer cells than a mixture of CPT and DOX, while they displayed reduced toxicity to normal cells. Due to assembly and PEG modification, the NCs improved drug retention time and enhanced accumulation at the tumor site. More importantly, they significantly inhibited colorectal tumor growth (58.37%) in vivo, superior to the CPT+DOX mix (42.63%). Moreover, the NCs reduced the cardiac toxicity of free drugs. Therefore, the prepared PEGylated CPT-ss-DOX NCs hold great potential for clinical transformation and provide a novel method for the self-delivery of hydrophobic molecules in cancer therapy.

Relationship of dietary natural folate and synthetic folic acid co-exposure patterns with biological aging: findings from NHANES 2003-2018.

Background: The mandatory folic acid fortification program in the United States has inevitably exposed most Americans to both natural folate and synthetic folic acid. We aim to examine the association of dietary folate co-exposure patterns with biological aging indicators. Methods: A total of 18 889 participants were enrolled from 2003 to 2018. Dietary intake of folate from diverse sources was evaluated by 24-hour dietary recall. Biological aging indicators were developed based on age-related clinical indicators, including the phenotypic age (PA), Klemera-Doubal method (KDM), homeostatic dysregulation (HD), and allostatic load (AL). The unsupervised K-means clustering method, logistic regression model, and restricted cubic spline (RCS) regression model were used to explore the relationship of natural folate and synthetic folic acid co-exposure with biological aging indicators. Results: The results indicated that higher intake of total folate, dietary folate, and food natural folate was associated with lower PA [OR = 0.75 (0.64, 0.88); OR = 0.79 (0.70, 0.90); OR = 0.65 (0.57, 0.75)], KDM [OR = 0.63 (0.53, 0.75); OR = 0.80 (0.65, 0.98); OR = 0.62 (0.49, 0.77)], HD [OR = 0.69 (0.56, 0.84); OR = 0.78 (0.67, 0.92); OR = 0.78 (0.68, 0.90)], and AL [OR = 0.69 (0.58, 0.82); OR = 0.73 (0.63, 0.85); OR = 0.74 (0.62, 0.90)], consistently. Four co-exposure patterns were generated based on the intake of folate from diverse sources, as follows: "low folate exposure group" to cluster 1, "dietary folate exposure group" to cluster 2, "mixed source high folate exposure group" to cluster 3, and "mixed source excessive folate exposure group" to cluster 4. Compared with cluster 1, participants in cluster 2 are associated with lower biological age indicators (ORPA = 0.82 [0.72, 0.93]; ORKDM = 0.58 [0.47, 0.70]; ORHD = 0.85 [0.75, 0.97]; ORAL = 0.87 [0.77, 0.98]), while participants in cluster 3 and cluster 4 are not. Conclusion: For individuals subjected to folic acid fortification programs, a higher intake of dietary folate, especially natural folate, coupled with a lower consumption of folic acid supplements, was found to be associated with lower biological age indicators.

Quantifying the reproducibility and longitudinal repeatability of radiomics features in magnetic resonance Image-Guide accelerator Imaging: A phantom study.

OBJECTIVE: This study aimed to quantitatively evaluate the inter-platform reproducibility and longitudinal acquisition repeatability of MRI radiomics features in Fluid-Attenuated Inversion Recovery (FLAIR), T2-weighted (T2W), and T1-weighted (T1W) sequences on MR-Linac systems using an American College of Radiology (ACR) phantom. MATERIALS AND METHODS: This study used two MR-Linac systems (A and B) in different cancer centers. The ACR phantom was scanned on system A daily for 30 consecutive days to evaluate longitudinal repeatability. Additionally, retest data were collected after repositioning the phantom. Inter-platform reproducibility was assessed by conducting scans under identical conditions using system B. Regions of interest were delineated on the T1W sequence from system A and mapped to other sequences via rigid registration. Intra-observer and inter-observer comparisons were conducted. Repeatability and reproducibility were assessed using the intraclass correlation coefficient (ICC) and coefficient of variation (CV). Robust radiomics features were identified based on ICC>0.9 and CV<10 %. RESULTS: Analysis showed that a higher proportion of radiomics features derived from longitudinal FLAIR sequence (51.65 %) met robustness criteria compared to T2W (48.35 %) and T1W (43.96 %). Additionally, more inter-platform features from the FLAIR sequence (62.64 %) were robust compared to T2W (42.86 %) and T1W (39.56 %). Test-retest and intra-observer repeatability were excellent across all sequences, with a median ICC of 0.99 and CV<5%. However, inter-observer reproducibility was inferior, especially for the T1W sequence. CONCLUSIONS: Different sequences show variations in repeatability and reproducibility. The FLAIR sequence demonstrated advantages in both longitudinal repeatability and inter-platform reproducibility. Caution is warranted when interpreting data, particularly in longitudinal or multiplatform radiomics studies.

Repurposing Niclosamide to Modulate Renal RNA-Binding Protein HuR for the Treatment of Diabetic Nephropathy in db/db Mice.

Hu antigen R (HuR) plays a key role in regulating genes critical to the pathogenesis of diabetic nephropathy (DN). This study investigates the therapeutic potential of niclosamide (NCS) as an HuR inhibitor in DN. Uninephrectomized mice were assigned to four groups: normal control; untreated db/db mice terminated at 14 and 22 weeks, respectively; and db/db mice treated with NCS (20 mg/kg daily via i.p.) from weeks 18 to 22. Increased HuR expression was observed in diabetic kidneys from db/db mice, which was mitigated by NCS treatment. Untreated db/db mice exhibited obesity, progressive hyperglycemia, albuminuria, kidney hypertrophy and glomerular mesangial matrix expansion, increased renal production of fibronectin and a-smooth muscle actin, and decreased glomerular WT-1+-podocytes and nephrin expression. NCS treatment did not affect mouse body weight, but reduced blood glucose and HbA1c levels and halted the DN progression observed in untreated db/db mice. Renal production of inflammatory and oxidative stress markers (NF-κBp65, TNF-a, MCP-1) and urine MDA levels increased during disease progression in db/db mice but were halted by NCS treatment. Additionally, the Wnt1-signaling-pathway downstream factor, Wisp1, was identified as a key downstream mediator of HuR-dependent action and found to be markedly increased in db/db mouse kidneys, which was normalized by NCS treatment. These findings suggest that inhibition of HuR with NCS is therapeutic for DN by improving hyperglycemia, renal inflammation, and oxidative stress. The reduction in renal Wisp1 expression also contributes to its renoprotective effects. This study supports the potential of repurposing HuR inhibitors as a novel therapy for DN.

Immune Characteristics and Immunotherapy of HIV-Associated Lymphoma.

In the era of antiretroviral therapy (ART), mortality among people living with the human immunodeficiency virus (HIV) has significantly decreased, yet the population of people living with HIV remains substantial. Among people living with HIV (PLWH), HIV-associated lymphoma (HAL) has surpassed Kaposi's sarcoma to become the most common tumor in this population in developed countries. However, there remains a dearth of comprehensive and systematic understanding regarding HIV-associated lymphomas. This review aims to shed light on the changes in the immune system among PLWH and the characteristics of the immune microenvironment in HIV-associated lymphoma, with a specific focus on the immune system's role in these individuals. Additionally, it seeks to explore recent advancements in immunotherapy for the treatment of HIV-associated lymphoma, intending to enhance strategies for immunotherapy in this specific population.

Specific growth velocity reference charts for monochorionic twin pregnancies.

OBJECTIVE: We aimed to create specific growth velocity reference charts for monochorionic (MC) twin pregnancies and provide additional information for assessing fetal growth in MC twins. STUDY DESIGN: This retrospective study collected data from uncomplicated MC twins with serial ultrasound parameters. The four ultrasound parameters, including biparietal diameter, femur length, head circumference, and abdominal circumference, were used to calculate the estimated fetal weight (EFW). Multilevel linear regression models were applied to fit growth velocity charts for each biometric parameter and EFW. Analysis of variance was used to examine differences in birthweight by whether EFW velocity and EFW values were <10th or ≥10th percentiles. RESULTS: The final analysis encompassed a total of 5956 ultrasound examinations conducted on 487 MC twins. The growth velocity of four biparietal diameters exhibited a gradual decrease in a nearly linear fashion progressing from 18 to 37 gestational weeks. The EFW velocity increased steadily from 18 to 36 gestational weeks, reaching a peak of 178.2 g/week, and then the velocity gradually decreased until delivery. At 32 weeks for illustration, the lightest birth weight was observed when both EFW and EFW velocity were <10th percentile (1899 g). The study also found that birth weight was higher when EFW velocity was ≥10th percentile compared with <10th percentile, regardless of EFW being below or above the 10th percentile (2263 and 1906 g, respectively; P < 0.001). CONCLUSION: We developed specific growth velocity reference charts for MC twins, which could provide a valuable reference point for a more precise evaluation of fetal growth in MC twins. Preliminary findings indicate that the inclusion of fetal growth velocity in monitoring fetal growth provides additional information beyond EFW alone.

Divergent Synthesis and Antigenicity Evaluation of Core Oligosaccharides of the Lipopolysaccharides from Acinetobacter baumannii SMAL and ATCC 19606.

Acinetobacter baumannii poses a serious threat to human health. Pathogenic bacterial lipopolysaccharides (LPSs) are potent immunogens for the development of antibacterial vaccines. To investigate the antigenic properties of A. baumannii LPS, five well-defined core oligosaccharide fragments from the LPS of A. baumannii SMAL and ATCC 19606 were synthesized. A divergent synthesis strategy based on orthogonally protected α-(2 → 5)-linked Kdo dimer 6 was developed. Selective exposure of different positions in this key precursor and then elongation of sugar chains via stereocontrolled formation of both 1,2-trans and 1,2-cis-2-aminoglycosidic linkages permitted the efficient synthesis of the targets. The synthetic route also highlights a 4-O and then 7-O glycosylation sequence for assembly of the novel 4,7-branched Kdo framework. Antigenicity assay using the glycan microarray technique disclosed that tetrasaccharide 3 featuring both 4,7-branch and α-(2 → 5)-Kdo-Kdo structural elements was a potential antigenic determinant.

[Analysis of Spatial Distribution of Ecosystem Services and Driving Factors in Northeast China].

Northeast China is an important ecological barrier in China, and an in-depth understanding of the spatial distribution in ecosystem services （ESs）, and the driving factors is crucial for realizing the subsequent management and protection of ESs. In the study, we quantitatively assessed the characteristics of spatial distribution in ESs in Northeastern China using the InVEST, RWEQ, and RUSLE models and identified the driving factors of ESs spatial distribution in conjunction with the geodetector based on meteorological data, remote sensing data, and socio-economic data. The results showed that the spatial distribution of ESs in Northeast China had obvious spatial heterogeneity. The high values of habitat quality （HQ）, carbon sequestration （CS） services, and soil conservation （SC） services were mainly distributed in the northern part of the four eastern leagues of the Inner Mongolia Autonomous Region, the northern part of Heilongjiang Province, and the eastern part of Northeast China, which were high in fraction vegetation cover, and low values were mainly found in southwestern and eastern Heilongjiang Province, western Jilin Province, and western Liaoning Province. The high values of the water yield （WY） service and wind prevention and sand fixation （WPSF） service were distributed in the east of the Inner Mongolia Autonomous Region and the east of Liaoning Province. The high values of WY services and WPSF services were distributed in the eastern part of Northeast China and the four eastern provinces of the Inner Mongolia Autonomous Region. According to the geodetector results, slope had the strongest explanatory power for the spatial distribution of SC services with a q-value of 0.31, land use/cover change had the strongest explanatory power for the spatial distribution of HQ and CS services with q-values of 0.64 and 0.52, respectively, and fraction vegetation coverage and annual precipitation had the strongest explanatory power for the spatial distribution of WPSF and WY services with q-values of 0.24 and 0.64, respectively, and there were interactions among all the driving factors. The spatial distribution of ESs in Northeast China was mainly influenced by natural factors. The results will provide a scientific basis for subsequent management and enhancement of ESs in Northeast China.

Single Layer Control of Nanoscale Metal-Insulator Transition at the LaAlO3/SrTiO3 Interface.

Modern quantum device fabrication often requires precisely adding and removing materials in situ at nanoscales, which is challenging for high-quality correlated oxide devices. In this work, we present a novel nanofabrication method that remotely controls the interfacial metal-insulator transition at the LaAlO3/SrTiO3 interface by selectively removing an LaAlO3 overlayer using a diamond tip. Remarkably, we observe a large force window within which single atomic layer precision of control is achievable. Our results confirm the critical thickness and charge transfer mechanism through a layer-by-layer removal process at the interface. Additionally, high-quality nanodevices, including nanochannels and single electron transistors, are successfully fabricated using this method. This nonvolatile and high-precision nanofabrication method provides a promising oxide platform for quantum engineering by harnessing the rich electron correlations at the nanoscale.

The causal relationship between triglycerides and myocardial infarction: A two-sample Mendelian randomization.

The causal relationship between triglycerides and myocardial infarction (MI) was investigated using Mendelian randomization (MR) studies. Triglycerides were the exposure factor, and MI served as the outcome variable. Inverse variance weighting was used as the main analysis method, MR-Egger, and weight median as other analysis methods for MR analysis. In addition, heterogeneity test, level multivariate analysis, and sensitivity analysis were carried out. Inverse variance weighting results showed that the increase in triglyceride level affected the incidence of MI (OR = 1.287; 95% CI = 1.185-1.398; P = 1.988 × 10-9). Consistently, the results from all 3 methods indicated a statistically significant increase in the risk of MI with higher triglyceride levels (P < .05). The results showed that patients with high triglyceride levels had a higher incidence of MI, suggesting that MI should be prevented in the high triglyceride population.

Effect of "He Tiao Du Ren An Shen Acupuncture" on restless leg syndrome: A randomized trial.

BACKGROUND: This study aimed to observe the clinical effects of "He Tiao Du Ren An Shen Acupuncture" (HTDRAS Acupuncture) for treating restless leg syndrome (RLS). METHODS: We randomly divided 66 RLS patients into 2 groups: the observation group received "He Tiao Du Ren An Shen Acupuncture" and the control group received conventional acupuncture. All participants were treated once a day, 6 days a week, with 1 day off, for a total of 1 month. Clinical effectiveness of the 2 groups was compared, neurotransmitter levels, the International Restless Leg Syndrome Scale and the Hamilton Anxiety Scale were assessed in both groups. RESULTS: The curative effect in the observation group was better than that in the control group (P < .05). After treatment, the expression of 5-hydroxytryptamine in the observation group was higher than in the control group (P < .05). The International Restless Leg Syndrome Scale and Hamilton Anxiety Scale scores in observation group were lower than those in control group (P < .05). CONCLUSION: "He Tiao Du Ren An Shen Acupuncture" for RLS is significantly effective and safe. It can effectively improve the levels of 5-hydroxytryptamine in RLS patients, alleviate clinical symptoms and reduce anxiety. This treatment has a high clinical application value and is worthy of clinical promotion.

N-terminus GTPase domain of the cytoskeleton protein FtsZ plays a critical role in its adaptation to high hydrostatic pressure.

Studies in model microorganisms showed that cell division is highly vulnerable to high hydrostatic pressure (HHP). Disassembly of FtsZ filaments induced by HHP results in the failure of cell division and formation of filamentous cells in E. coli. The specific characteristics of FtsZ that allow for functional cell division in the deep-sea environments, especially in obligate piezophiles that grow exclusively under HHP condition, remain enigmatic. In this study, by using a self-developed HHP in-situ fixation apparatus, we investigated the effect of HHP on FtsZ by examining the subcellular localization of GFP-tagged FtsZ in vivo and the stability of FtsZ filament in vitro. We compared the pressure tolerance of FtsZ proteins from pressure-sensitive strain Shewanella oneidensis MR-1 (FtsZSo) and obligately piezophilic strain Shewanella benthica DB21MT-2 (FtsZSb). Our findings showed that, unlike FtsZSo, HHP hardly affected the Z-ring formation of FtsZSb, and filaments composed of FtsZSb were more stable after incubation under 50 MPa. By constructing chimeric and single amino acid mutated FtsZ proteins, we identified five residues in the N-terminal GTPase domain of FtsZSb whose mutation would impair the Z-ring formation under HHP conditions. Overall, these results demonstrate that FtsZ from the obligately piezophilic strain exhibits superior pressure tolerance than its homologue from shallow water species, both in vivo and in vitro. Differences in pressure tolerance of FtsZ are largely attributed to the N-terminal GTPase domain. This represents the first in-depth study of the adaptation of microbial cytoskeleton protein FtsZ to high hydrostatic pressure, which may provide insights into understanding the complex bioprocess of cell division under extreme environments.

Serum amyloid A1 induced dysfunction of airway macrophages via CD36 pathway in allergic airway inflammation.

Previous studies showed that serum amyloid A (SAA) and macrophages were associated with allergic airway inflammation. However, the interaction between SAA1 and macrophages in allergic airway inflammation remains to be further elucidated. In this study, the levels of SAA1 were measured in nasal tissues from patients with eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), house dust mite (HDM)-treated BEAS-2B cells and the tissues of mice of HDM-induced allergic airway inflammation. Human monocytes-derived macrophages and mouse bone marrow-derived macrophages (BMDMs) were exposed to SAA1, and CCL17 and the other M1/M2-related factors were evaluated using RT-PCR and/or ELISA. To test the effects of SAA1-treated BMDMs on chemotaxis and differentiation of CD4+ T cells, number of migrated cells and the levels of Th1 and Th2 were measured using flow cytometry. SAA1 receptors were examined in BMDMs and lung macrophages of model mice. CD36 neutralizing antibody was applied to explore the mechanisms of SAA1 in regulating BMDMs using RT-PCR and/or ELISA. We found that SAA1 was expressed in epithelial cells, and was increased in the nasal tissues of patients with eosinophilic CRSwNP and HDM-treated BEAS-2B- cells as well as the bronchoalveolar lavage fluid and lung tissues of mice exposed to HDM. We also found that the level of CCL17 was increased in M2 macrophages, more CD4+ T cells were recruited and proportion of Th2 was increased after the treatment of SAA1. The treatment of CD36 neutralizing antibody decreased CCL17 level in SAA1-treated M2 BMDMs. In summary, our results showed that SAA1 was increased in allergic airway inflammation, and the administration of SAA1 upregulated the expression of CCL17 in M2 macrophages via CD36 and promoted the chemotaxis of CD4+ T cells and differentiation of Th2. It may provide a new therapeutic strategy that could mediate allergic airway inflammation via suppressing SAA1 to reduce recruitment of CD4+ T cells and activation of Th2.

Increased circulating LOX-1+ neutrophils activate T cells and demonstrate a pro-inflammatory role in allergic rhinitis.

Background: Low-density neutrophils are heterogeneous immune cells with immunosuppressive (such as polymorphonuclear myeloid-derived suppressor cells [PMN-MDSC]) or pro-inflammatory (such as low-density granulocytes [LDG]) properties that have been well described in multiple cancers and immune diseases. However, its role in allergic rhinitis (AR) is still unclear. Methods: In the present study, we defined low-density neutrophils as CD14-CD11B+CD15+LOX-1+ (LOX-1+ neutrophils), and their levels in the peripheral blood (PB) were evaluated and compared between patients with AR and healthy donors using flow cytometric analysis. LOX-1 expression on polymorphonuclear neutrophils was identified. Carboxyfluorescein succinimidyl ester (CFSE)-stained CD3+ T cells were cultured alone or with LOX-1+ neutrophils, T cell proliferation was assessed using flow cytometry, and pro-inflammatory cytokines in the supernatants were detected using enzyme-linked immunosorbent assay (ELISA). Clinicopathological analyses were performed to gain a thorough understanding of LOX-1+ neutrophils. Results: We determined that LOX-1+ neutrophils were significantly increased in the PB of patients with AR, and LOX-1 expression in neutrophils from patients with AR was elevated. Interestingly, LOX-1+ neutrophils derived from patients with AR, unlike PMN-MDSC, promoted T cell proliferation and pro-inflammatory cytokine production. Moreover, clinicopathological analysis revealed that there was no any relation between circulating LOX-1+ neutrophil levels and the levels of IgE, age and sex. Conclusion: These findings indicate that elevated circulating LOX-1+ neutrophils play a pro-inflammatory role in AR.

Analysis of the Dynamic Expression of the SMAD Family in the Periosteum During Guided Bone Regeneration.

OBJECTIVE: The aim of this study was to investigate the dynamic expression of the SMAD family during guided bone regeneration for the reconstruction of cranio-maxillofacial bone defects. METHODS: A swine model of guided bone regeneration was established with one side of the rib as the trauma group and the contralateral as control group. Periosteal and regenerative tissue specimens were harvested at 9 time points in the early, middle, and late phases, and were subjected to gene sequencing and tissue staining. Expression data of each SMAD family were extracted for further analysis, in which the correlation of the expression of the respective members within and between groups and at different time points was analyzed. RESULTS: The expression of individual members of the SMAD family fluctuates greatly, especially during the first month. The SMAD3 and SMAD4 genes were the most highly expressed. The foldchange value of SMAD6 was the largest and remained above 1.5 throughout the process. The dynamic expression levels of SMAD2, SMAD4, SMAD5, SMAD6, and SMAD9 showed a significant positive correlation in both groups. The expression levels of each gene showed a positive correlation with other SMAD genes. Tissue staining showed that the overall contour of the regenerated bone tissue was basically formed within the first 1 month. CONCLUSION: The first month of guided bone regeneration is a critical period for bone regeneration and is an important period for the SMAD family to play a role. The SMAD6 may play an important role in the whole process of guided bone regeneration.

Enhanced production of health-promoting phenolic compounds using a novel endophytic fungus Talaromyces neorugulosus R-209 isolated from pigeon pea in a natural habitat by l-phenylalanine feeding.

In this study, nine endophytic fungi capable of producing multiple phenolic compounds were screened and identified from 152 fungi isolated from pigeon pea in a natural habitat (Honghe, Yunnan Province, China). Talaromyces neorugulosus R-209 exhibited the highest potential for phenolic compound production. L-phenylalanine feeding was used to enhance phenolic compound production in T. neorugulosus R-209 cultures. Under the optimal feeding conditions (l-phenylalanine dose of 0.16 g/L and feeding phase of 6 days), the yields of genistein, apigenin, biochanin A, and cajaninstilbene acid increased by 15.59-fold, 7.20-fold, 25.93-fold, and 10.30-fold over control, respectively. T. neorugulosus R-209 fed with l-phenylalanine was found to be stable in the production of phenolic compounds during ten successive subcultures. Moreover, bioactivities of extracts of T. neorugulosus R-209 cultures were significantly increased by l-phenylalanine feeding. Overall, l-phenylalanine feeding strategy made T. neorugulosus R-209 more attractive as a promising alternative source for the production of health-beneficial phenolic compounds in the nutraceutical/medicinal industries.

Clinical and pathogen features of COVID-19-associated infections during an Omicron strain outbreak in Guangzhou, China.

Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens. IMPORTANCE: Our study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.