SIRT6 Inhibits the Proliferation and Collagen Synthesis of Keloid Fibroblasts through MAPK/ERK Pathway.

BACKGROUND: Keloid, a fibroproliferative disorder, significantly impacts patients' quality of life, yet effective therapies remain elusive. This study explored the role of silent information regulator 6 (SIRT6) in modulating the proliferation, invasion, and collagen synthesis of keloid fibroblasts. METHODS: Keloid and normal skin specimens were collected, and fibroblasts were isolated from the keloid tissue. SIRT6 recombinant adenovirus (Ad) was constructed to infect keloid fibroblasts to overexpress SIRT6. This study entails three groups: Control group, adenovirus-Negative Control (Ad-NC) group, and Ad-SIRT6 group. SIRT6 protein and mRNA levels were measured via Western blotting and Quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. Cell viability was determined using 5-ethynyl-2'-deoxyuridine (EdU) assay. Flow cytometry was exploited to measure cell apoptosis. To investigate cell migration, wound healing assay and Transwell assay were employed. Western blotting was also utilized to study the expression levels of apoptotic proteins, collagen deposition-related proteins, and Mitogen-Activated Protein Kinases (MAPK)/extracellular regulated protein kinases (ERK) pathway-related proteins. RESULTS: Compared to the control and Ad-NC groups, the Ad-SIRT6 group exhibited significantly elevated SIRT6 level; diminished cell proliferation, migration and invasion; reduced protein levels of α-smooth muscle actin (α-SMA), collagen I, collagen III, phospho SMAD Family Member 3 (p-Smad3), transforming growth factor-ß 1 (TGF-ß1), and MAPK/ERK pathway proteins (phospho extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phospho MAP kinase-ERK kinase (p-MEK) and phospho-c-Raf (p-c-Raf)). Treatment with epidermal growth factor (EGF), an MAPK/ERK pathway agonists, reversed the inhibitory effect of SIRT6 on cell activity and inhibited apoptosis in keloid fibroblasts. CONCLUSION: SIRT6 overexpression in keloid fibroblasts attenuates proliferation, invasion, and collagen synthesis, while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity. This suggests a potential therapeutic target for keloid treatment.

Unraveling the impact of Spartina alterniflora invasion on greenhouse gas production and emissions in coastal saltmarshes: New insights from dissolved organic matter characteristics and surface-porewater interactions.

Saltmarshes along the Chinese coast are threatened by the invasion of Spartina alterniflora (S. alterniflora). This study was carried out in the Andong Shoal, Hangzhou Bay, China, with the aim of comprehending the intricate impacts of S. alterniflora invasion on greenhouse gases (GHG) production and emissions. To address this issue, we thoroughly examined the chemistry of dissolved organic matter (DOM) and the rate of surface water-porewater interaction. Porewater and surface water samples were collected from farm land, S. alterniflora invaded areas, and Scirpus mariqueter (S. mariqueter) dominated areas. The findings indicated that the invasion of S. alterniflora impeded the interaction between surface water and porewater, resulting in reduced porewater exchange rates within its affected region (0.015-0.440 cm d-1), in contrast to areas dominated by S. mariqueter (9.635-18.232 cm d-1). The invasion also increased dissolved organic carbon concentration in porewater and created a stable and closed soil environment that resulted in DOM with smaller molecule sizes and higher humification levels. The presence of high tryptophan-like fluorescent DOM caused an increase in the production of methane and carbon dioxide in S. alterniflora invaded area. However, both limited surface-porewater exchange and significant differences in GHG concentrations between porewater and surface water suggested that the aerenchyma tissues of S. alterniflora may play an important role in transporting GHG from soil to the atmosphere.

A Novel Deep-Trench Super-Junction SiC MOSFET with Improved Specific On-Resistance.

In this paper, a novel 4H-SiC deep-trench super-junction MOSFET (Metal-Oxide-Semiconductor Field-Effect Transistor) with a split-gate is proposed and theoretically verified by Sentaurus TCAD simulations. A deep trench filled with P-poly-Si combined with the P-SiC region leads to a charge balance effect. Instead of a full-SiC P region in conventional super-junction MOSFET, this new structure reduces the P region in a super-junction MOSFET, thus helping to lower the specific on-resistance. As a result, the figure of merit (FoM, BV2/Ron,sp) of the proposed new structure is 642% and 39.65% higher than the C-MOS and the SJ-MOS, respectively.

Comparison of groundwater storage changes over losing and gaining aquifers of China using GRACE satellites, modeling and in-situ observations.

Groundwater depletion in intensively exploited aquifers of China has been widely recognized, whereas an overall examination of groundwater storage (GWS) changes over major aquifers remains challenging due to limited data and notable uncertainties. Here, we present a study to explore GWS changes over eighteen major aquifers covering an area of 1,680,000 km2 in China using data obtained from the Gravity Recovery and Climate Experiments (GRACE), global models, and in-situ groundwater level observations. The analysis aims to reveal the discrepancy in annual trends, amplitudes, and phases associated with GWS changes among different aquifers. It is found that GWS changes in the studied aquifers represent a spatial pattern of 'Wet-gets-more, Dry-gets-less'. An overall decreasing trend of -4.65 ± 0.34 km3/yr is observed by GRACE from 2005 to 2016, consisting of a significant (p < 0.05) increase of 47.28 ± 3.48 km3 in 7 aquifers and decrease of 103.56 ± 2.4 km3 (∼2.6 times the full storage capacity of the Three Gorges Reservoir) in 10 aquifers summed over the 12 years. The annual GWS normally reaches a peak in late July with an area-weighted average annual amplitude of 19 mm, showing notable discrepancy in phases and amplitudes between the losing aquifers (12 mm in middle August) in northern China and gaining aquifers (28 mm in early July) mostly in southern China. GRACE estimates are generally comparable, but can be notably different, with the results obtained from model simulations and in-situ observations at aquifer scale, with the area-weighted average correlation coefficients of 0.6 and 0.5, respectively. This study highlights different GWS changes of losing and gaining aquifers in response to coupled impacts of hydrogeology, climate and human interventions, and calls for divergent adaptions in regional groundwater management.

A Model to Predict Prognosis of Renal Cell Clear Cell Carcinoma Based on 3 Angiogenesis-related Long Non-coding RNAs.

Background: Tumor angiogenesis is closely related to the progression of clear cell renal cell carcinoma (ccRCC). Long non-coding RNAs (lncRNAs) regulating angiogenesis could be potential biomarkers for predicting ccRCC prognosis. With this study, we aimed to construct a prognostic model based on lncRNAs and explore its underlying mechanisms. Methods: RNA data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Angiogenesis-related genes (ARGs) were extracted from the Molecular Signatures database. Pearson correlation and LASSO and COX regression analyses were performed to identify survival-related AR-lncRNAs (sAR-lncRNAs) and construct a prognostic model. The predictive power of the prognostic model was verified according to Kaplan‒Meier curve, receiver operating characteristic (ROC) curve and nomogram analyses. The correlation between the prognostic model and clinicopathological characteristics was assessed via univariate and multivariate analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was subsequently performed to elucidate the mechanisms of the sAR-lncRNAs. In vitro qPCR, immunohistochemistry, migration and invasion assays were conducted to confirm the angiogenic function of sAR-lncRNAs. Results: Three sAR-lncRNAs were used to construct a prognostic model. The model was moderately accurate in predicting 1- , 3- and 5-year ccRCC prognosis, and the risk score according to this model was closely related to clinicopathological characteristics such as T grade and T stage. A nomogram was constructed to precisely estimate the overall survival of ccRCC patients. KEGG enrichment analysis indicated that the MAPK and Notch pathways were highly enriched in high-risk patients. Additionally, we found that the expression of the lncRNAs AC005324.4 and AC104964.4 in the prognostic model was lower in ccRCC cell lines and cancer tissues than in the HK-2 cell line and paracancerous tissues, while the expression of the lncRNA AC087482.1 showed the opposite trend. In a coculture model, knockdown of lncRNA AC005324.4 and lncRNA AC104964.4 significantly promoted the migration and invasion of human umbilical vein endothelial cells (HUVECs), but siR-AC087482.1 transfection alleviated these effects. Conclusions: We constructed a prognostic model based on 3 sAR-lncRNAs and validated its value in clinicopathological characteristics and prognostic prediction of ccRCC patients, providing a new perspective for ccRCC treatment decision making.

CBX4 plays a bidirectional role in transcriptional regulation and lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality worldwide. Understanding the dysregulated epigenetics governing LUAD progression is pivotal for identifying therapeutic targets. CBX4, a chromobox protein, is reported to be upregulated in LUAD. This study highlights the dual impact of CBX4 on LUAD proliferation and metastasis through a series of rigorous in vitro and in vivo experiments. Further investigation into the underlying mechanism through high-throughput ChIP-seq and RNA-seq reveals that CBX4 functions in promoting LUAD proliferation via upregulating PHGDH expression and subsequent serine biosynthesis, while concurrently suppressing LUAD metastasis by inhibiting ZEB2 transcription. CBX4 facilitates PHGDH transcription through the interaction with GCN5, inducing heightened histone acetylation on the PHGDH promoter. Simultaneously, the inhibition of ZEB2 transcription involves CBX4-mediated recruitment of canonical PRC1 (cPRC1), establishing H2K119ub on the ZEB2 promoter. These findings underscore CBX4's pivotal role as a regulator of LUAD progression, emphasizing its diverse transcriptional regulatory functions contingent upon interactions with specific epigenetic partners. Understanding the nuanced interplay between CBX4 and epigenetic factors sheds light on potential therapeutic avenues in LUAD.

BiU-net: A dual-branch structure based on two-stage fusion strategy for biomedical image segmentation.

BACKGROUND AND OBJECTIVE: Computer-based biomedical image segmentation plays a crucial role in planning of assisted diagnostics and therapy. However, due to the variable size and irregular shape of the segmentation target, it is still a challenge to construct an effective medical image segmentation structure. Recently, hybrid architectures based on convolutional neural networks (CNNs) and transformers were proposed. However, most current backbones directly replace one or all convolutional layers with transformer blocks, regardless of the semantic gap between features. Thus, how to sufficiently and effectively eliminate the semantic gap as well as combine the global and local information is a critical challenge. METHODS: To address the challenge, we propose a novel structure, called BiU-Net, which integrates CNNs and transformers with a two-stage fusion strategy. In the first fusion stage, called Single-Scale Fusion (SSF) stage, the encoding layers of the CNNs and transformers are coupled, with both having the same feature map size. The SSF stage aims to reconstruct local features based on CNNs and long-range information based on transformers in each encoding block. In the second stage, Multi-Scale Fusion (MSF), BiU-Net interacts with multi-scale features from various encoding layers to eliminate the semantic gap between deep and shallow layers. Furthermore, a Context-Aware Block (CAB) is embedded in the bottleneck to reinforce multi-scale features in the decoder. RESULTS: Experiments on four public datasets were conducted. On the BUSI dataset, our BiU-Net achieved 85.50 % on Dice coefficient (Dice), 76.73 % on intersection over union (IoU), and 97.23 % on accuracy (ACC). Compared to the state-of-the-art method, BiU-Net improves Dice by 1.17 %. For the Monuseg dataset, the proposed method attained the highest scores, reaching 80.27 % and 67.22 % for Dice and IoU. The BiU-Net achieves 95.33 % and 81.22 % Dice on the PH2 and DRIVE datasets. CONCLUSIONS: The results of our experiments showed that BiU-Net transcends existing state-of-the-art methods on four publicly available biomedical datasets. Due to the powerful multi-scale feature extraction ability, our proposed BiU-Net is a versatile medical image segmentation framework for various types of medical images. The source code is released on (https://github.com/ZYLandy/BiU-Net).

ReaxFF-Based Molecular Dynamics Study of the Mechanism of the Reaction of N2O4 with H2O.

During long-term storage of the liquid propellant N2O4, it absorbs H2O to form the N2O4(H2O)n system, and this in turn generates HNO3, HNO2, and other substances in the storage tank because of corrosion, which seriously affects the performance of weaponry. In this work, we carried out computational simulations of N2O4 with different masses of water based on ReaxFF, analyzed the reaction intermediates and products, and investigated the mechanism of the reaction of N2O4 with H2O and of N2O4(H2O)n. The results show that the reaction product ω(HNO3+HNO2) undergoes a rapid growth in the early stage of the reaction and then tends toward dynamic equilibrium; the potential energy of the system decreases with the increase of ω(H2O), the reaction rate increases, and the rate of decomposition of HNO2 to form HNO3 increases. When ω(H2O) is 0.2 or 1.0%, the intermediate products are N2O4H2O or N2O4(H2O)2, respectively, and the reaction proceeds along two paths; when ω(H2O) ≥ 2.0%, N2O4(H2O)3 appears as the intermediate product, HNO3 and HNO2 are directly produced in one step, and a stable current loop can be formed within the whole system.

Rapid in-situ aerobic biodegradation of high salt and oily food waste employing constructed synthetic microbiome.

The high salt content of food waste (FW) severely limits microbial physiological activity and reduces its biodegradability. In this study, a salt-tolerant thermophilic bacterial agent that consists of four different substrate degradation functional strains was evaluated for efficient high salt and oily FW in solid-state aerobic biodegradation disposers. The phy-chemical properties, enzyme activities, microbial community structure, and function during the biodegradation process were evaluated under high salt (5%) stress. The results showed that the agent promoted the degradation rate, increased the matrix temperature, decreased the moisture content (MC), and enhanced enzyme activities without putrid smell. High-throughput sequencing indicated community structure succession between different groups and the positive contribution of the inoculated functional strains. During the FW biodegradation process, the Bacillus sp. inoculated was the dominant genus in the agent group. Furthermore, CCA further confirmed the positive effects of the four inoculated strains on high salt and oily FW aerobic biodegradation. Functional prediction and metabolite results both confirmed that the agent was more efficient in carbon, amino acid, and lipid metabolism, which demonstrated that the synthetic microbial consortium holds a potential advantage for efficiency and subsequent resource utilization for organic fertilizer.

FOXP4-AS1 promotes CD8+ T cell exhaustion and esophageal cancer immune escape through USP10-stabilized PD-L1.

Esophageal cancer (EC) is the 9th most frequently diagnosed malignancy globally with unfavorable prognosis. Immune escape is one of the principal factors leading to poor survival, however, the mechanism underlying immune escape remains largely uninvestigated. The xenograft mouse model and EC cell-CD8+ cytotoxic T lymphocytes (CTLs) co-culture system were established. Immunohistochemistry, qRT-PCR or western blot were employed to detect the levels of long non-coding RNA (lncRNA) FOXP4-AS1, PD-L1, USP10 and other molecules. The abundance of T cells, cytokine production and cell apoptosis were monitored by flow cytometry. The viability of CTLs was assessed by Trypan blue staining. The binding between FOXP4-AS1 and USP10 was validated by RNA pull-down assay, and the interaction between USP10 and PD-L1, as well as the ubiquitination of PD-L1, were detected by co-immunoprecipitation. The elevation of FOXP4-AS1 in EC was associated with decreased CTL abundance, and upregulated PD-L1 facilitated CTL apoptosis in EC. FOXP4-AS1 accelerated EC tumor growth by decreasing the abundance of tumor infiltrating CTLs in vivo. FOXP4-AS1 inhibited the viability of CTLs and facilitated the cytotoxicity and exhaustion of CTLs. In Kyse 450 cell-CTL co-culture system, FOXP4-AS1 suppressed the viability and abundance of CTLs, and inhibited EC cell apoptosis via PD-L1. Mechanistically, FOXP4-AS1 regulated the ubiquitination of PD-L1 through deubiquitinating enzyme USP10. FOXP4-AS1 promoted CTL exhaustion and EC immune escape through USP10-stabilized PD-L1. HIGHLIGHTS: PD-L1 facilitated CD8+ T cell apoptosis in EC. Upregulated FOXP4-AS1 promoted EC tumor growth by inhibiting the viability and facilitating the cytotoxicity and exhaustion of tumor infiltrating CD8+ T cells. FOXP4-AS1 suppressed the viability and abundance of CD8+ T cells through USP10-mediated deubiquitination of PD-L1.

Granulathiazole A protects 6-OHDA-induced Parkinson's disease from ferroptosis via activating Nrf2/HO-1 pathway.

Two pairs of enantiomers (1a-2b), namely (±)-alterpyrone F and (±)-alterpyrone G, along with a rare benzothiazole meroterpenoid granulathiazole A (3, GA), and two undescribed compounds called respectively granulahydeoate (4) and granulaone (5), were obtained from the co-cultivation of Alternaria brassicicola and Penicillium sp. HUBU0120. Exhaustive analyses of NMR, single crystal XRD, Mo2(OAc)4-induced circular dichroism data, and a modified Mosher's method distinguished the absolute configurations of isolates. Bioactive evaluations exhibited that GA possessed promising anti-PD activity in both in vitro and in vivo PD models viz. 6-OHDA-induced SH-SY5Y cells and 6-OHDA-induced zebrafish, respectively. Moreover, our research demonstrated that ferroptosis activated by 6-OHDA was mitigated in PD models after treated with GA. Extensive molecular mechanism studies in PD-modelled cells manifested that GA attenuated the decreased expressions of SLC7A11, GPX4, and FSP-1, and the increased level of ACSL4 via activating Nrf2/HO-1 pathway as well as ameliorated the accumulation of α-synuclein.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Functional near-infrared spectroscopy-based diagnosis support system for distinguishing between mild and severe depression using machine learning approaches.

Significance: Early diagnosis of depression is crucial for effective treatment. Our study utilizes functional near-infrared spectroscopy (fNIRS) and machine learning to accurately classify mild and severe depression, providing an objective auxiliary diagnostic tool for mental health workers. Aim: Develop prediction models to distinguish between severe and mild depression using fNIRS data. Approach: We collected the fNIRS data from 140 subjects and applied a complete ensemble empirical mode decomposition with an adaptive noise-wavelet threshold combined denoising method (CEEMDAN-WPT) to remove noise during the verbal fluency task. The temporal features (TF) and correlation features (CF) from 18 prefrontal lobe channels of subjects were extracted as predictors. Using recursive feature elimination with cross-validation, we identified optimal TF or CF and examined their role in distinguishing between severe and mild depression. Machine learning algorithms were used for classification. Results: The combination of TF and CF as inputs for the prediction model yielded higher classification accuracy than using either TF or CF alone. Among the prediction models, the SVM-based model demonstrates excellent performance in nested cross-validation, achieving an accuracy rate of 92.8%. Conclusions: The proposed model can effectively distinguish mild depression from severe depression.

The predictive value of next generation sequencing for matching advanced hepatocellular carcinoma patients to targeted and immunotherapy.

Background: Targeted and Immunotherapy has emerged as a new first-line treatment for advanced hepatocellular carcinoma (aHCC). To identify the appropriate targeted and immunotherapy, we implemented next generation sequencing (NGS) to provide predictive and prognostic values for aHCC patients. Methods: Pretreatment samples from 127 HCC patients were examined for genomic changes using 680-gene NGS, and PD-L1 expression was detected by immunohistochemistry. Demographic and treatment data were included for analyses of links among treatment outcomes, drug responses, and genetic profiles. A prognostic index model for predicting benefit from treatment was constructed, taking into account of biomarkers, including TP53, TERT, PD-L1, and tumor mutation burden (TMB) as possible independent prognostic factors. Results: The multivariate Cox regression analyses showed that PD-L1≥1% (HR 25.07, 95%CI 1.56 - 403.29, p=0.023), TMB≥5Mb (HR 86.67, 95% CI 4.00 - 1876.48, p=0.004), TERT MU (HR 84.09, 95% CI 5.23 - 1352.70, p=0.002) and TP53 WT (HR 0.01, 95%CI 0.00 - 0.47, p=0.022) were independent risk factors for overall survival (OS), even after adjusting for various confounders. A prognostic nomogram for OS was developed, with an area under the ROC curve of 0.91, 0.85, and 0.98 at 1-, 2-, and 3- year, respectively, and a prognostic index cutoff of 1.2. According to the cutoff value, the patients were divided into the high-risk group (n=29) and low-risk group (n=98). The benefit of targeted and immunotherapy in the low-risk group was not distinguishable according to types of agents. However, treatment of Atezolizumab and Bevacizumab appeared to provide longer OS in the high-risk group (12 months vs 9.2, 9, or 5 months for other treatments, p<0.001). Conclusion: The prognostic model constructed by PD-L1, TMB, TERT, and TP53 can identify aHCC patients who would benefit from targeted and immunotherapy, providing insights for the personalized treatment of HCC.

Anatomical sectionectomy based on Takasaki's segmentation for solitary intrahepatic cholangiocarcinoma: a propensity-matched analysis.

BACKGROUND: Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown. METHODS: A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival. RESULTS: After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference. CONCLUSION: TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm.

The challenge of managing ischemic stroke in brucellosis: a case report.

A 64-year-old woman was admitted to the hospital for sudden weakness in one of her left limbs. The patient was diagnosed with acute ischemic stroke (IS) of undetermined cause and received intravenous thrombolysis. Following thrombolysis, the patient's left limb weakness improved, but she subsequently developed recurrent high fever and delirium. Further diagnostic tests revealed that she had been infected with Brucella melitensis. The patient showed significant improvement during anti-infection treatment for Brucellosis and secondary prevention treatment for IS. However, her condition unexpectedly worsened on the 44th day after admission due to a hemorrhagic stroke (HS), which required an urgent craniotomy. Immunohistochemical analysis of the hematoma sample collected during the operation showed the presence of CD4+ and CD8+ T lymphocytes surrounding the blood vessels. This case highlights the unique challenge of managing IS in brucellosis and sheds light on the potential role of T lymphocytes in the immune response related to stroke.

Genomic Insights and Synthetic Biology Applications of Marine Actinomycete Streptomyces griseoincarnatus HNS054.

The marine bacterium Streptomyces sp. HNS054 shows promise as a platform for producing natural products. Isolated from a marine sponge, HNS054 possesses several desirable traits for bioengineering: rapid growth, salt tolerance, and compatibility with genetic tools. Its genome contains 21 potential biosynthetic gene clusters, offering a rich source of natural products. We successfully engineered HNS054 to increase the production of aborycin and actinorhodin by 4.5-fold and 1.2-fold, respectively, compared to S. coelicolor M1346 counterparts. With its unique features and amenability to genetic manipulation, HNS054 emerges as a promising candidate for developing novel marine-derived drugs and other valuable compounds.

Liver resection versus microwave ablation for solitary and small (≤ 3 cm) HCC with early recurrence in different stages of liver cirrhosis: A propensity score matching study.

BACKGROUND: This study aimed to compare the effectiveness of liver resection (LR) and microwave ablation (MWA) in hepatocellular carcinoma (HCC) patients with early recurrence and varying stages of cirrhosis. METHOD: This study analyzed patients with HCC who underwent hepatectomy and experienced early tumor recurrence (≤3 cm) between December 2002 and December 2020 at the Tongji Hospital. Treatment effectiveness was assessed using a propensity score matching (PSM) analysis. RESULTS: This study included 295 patients (106, LR; 189, MWA), 86 patients in each of the 2 groups were chosen for further comparison, after PSM. After PSM, both LR and MWA demonstrated similar recurrence-free survival (RFS) and overall survival (OS) rates (p = 0.060 and p = 0.118, respectively). However, the LR group had more treatment-related complications. In patients with moderate or severe cirrhosis, no significant differences in RFS or OS rates were found between the LR and MWA groups (p = 0.779 and p = 0.772, respectively). In patients without cirrhosis or with mild cirrhosis, LR showed better RFS and OS rates than MWA (p = 0.024 and p = 0.047, respectively). Multivariate analysis after PSM identified moderate or severe cirrhosis and recurrence intervals ≤12 months as independent predictors of poor RFS and OS in patients with early recurrence of HCC. CONCLUSION: LR is more effective than MWA for early recurrence of HCC in patients without cirrhosis or with mild cirrhosis, showing improved RFS and OS rates. In patients with moderate or severe cirrhosis, the OS and RFS were statistically equal between the two therapies. However, MWA may be preferred owing to its low complication rate.

Phenotypic correlations of carpal gland diverticular number with production traits and its genome-wide association analysis in multiple pig populations.

Pig carpal glands play crucial roles in territorial recognition, reproductive behavior, and information exchange; however, their effects on production traits and underlying genetic mechanisms remain unclear. In this study, 1028 pigs from six populations were counted for the carpal gland diverticular numbers (CGDNs) on the left (CGDNL) and right (CGDNR) legs, and their carcass and meat quality traits were assessed. The CGDNs were significantly different among the populations, and Licha Black pigs had a lower CGDN than the Bama Xiang breed. It was also significantly different between sexes, with males having more diverticula than females (p ≤ 0.0391). Moreover, the number was asymmetric, with CGDNR being significantly higher than CGDNL. Notably, CGDNs was significantly correlated with each other in phenotype and genetics and with 24-h pH, 24-h meat color score, 24-h marbling score, fat content, moisture content, sodium salt content, and saturated fatty acid content in phenotype. Furthermore, genome-wide association analyses identified seven SNPs in association with CGDNs at a 5% genome-wide significance level, all of which were located in a 1.78-Mb (35.347-37.129 Mb) region on chromosome 1. CNC10010837 and CNC10010840 were the top SNPs: both had an additive effect of 0.789 ± 0.120 on CGDNR with p = 8.31E-10. These findings provide important insights into the functions and underlying genetic mechanisms of swine carpal glands.

Nomograms confirm serum IL-6 and CRP as predictors of immune checkpoint inhibitor efficacy in unresectable hepatocellular carcinoma.

Background: Immunotherapy based on immune checkpoint inhibitors (ICIs) has become the first-line treatment for unresectable hepatocellular carcinoma (uHCC). However, only a small portion of patients are responsive to ICIs. It is important to identify the patients who are likely to benefit from ICIs in clinical practice. We aimed to examine the significance of serum IL-6 and CRP levels in predicting the effectiveness of ICIs for uHCC. Methods: We retrospectively recruited 222 uHCC patients who received ICIs treatment (training cohort: 124 patients, validation cohort: 98 patients). In the training cohort, patients are categorized into the response group (R) and no-response group (NR). The levels of serum IL-6 and CRP were compared between the two groups. Internal validation was performed in the validation cohort. Survival analysis was carried out using the Kaplan-Meier method and Cox proportional hazard regression model. The nomograms were developed and assessed using the consistency index (C-index) and calibration curve. Results: Serum levels of IL-6 and CRP were significantly lower in the R group than in the NR group (9.94 vs. 36.85 pg/ml, p< 0.001; 9.90 vs. 24.50 mg/L, p< 0.001, respectively). An ROC curve was employed to identify the optimal cut-off values for IL-6 and CRP in both groups, resulting in values of 19.82 pg/ml and 15.50 mg/L, respectively. Multivariate Cox regression analysis revealed that MVI (HR 1.751, 95%CI 1.059-2.894, p=0.029; HR 1.530, 95%CI 0.955-2.451, p=0.077), elevated IL-6 (HR 1.624, 95%CI 1.016-2.596, p=0.043; HR 2.146, 95%CI 1.361-3.383, p =0.001) and high CRP (HR 1.709, 95%CI 1.041-2.807, p=0.034; HR 1.846, 95%CI 1.128-3.022, p = 0.015) were independent risk factors for PFS and OS, even after various confounders adjustments. Nomograms are well-structured and validated prognostic maps constructed from three variables, as MVI, IL6 and CRP. Conclusion: Low levels of IL-6 and CRP have a positive correlation with efficacy for uHCC patients receiving ICIs.