Search

The fungal community structure, the relationship between fungal flora and physicochemical factors, and the prediction of fungal function in pit muds from different spatial positions of 10- and 50-year-old cellars at Jinhui liquor Co. Ltd. were studied by using Illumina NovaSeq high-throughput sequencing, redundancy analysis and Fungi Functional Guild (FUNGuild). The results showed that the fungal diversity and richness of the 10-year-old pit mud decreased with increasing depth; the fungal diversity of the 50-year-old pit mud showed an overall increasing trend, while the fungal richness initially decrease and then increased. Moreover, for the 10-year-old pit, the fungal diversity and richness of the upper layer of the pit wall were significantly higher than those of the other positions (P < 0.05), while for the 50-year-old cellar, the fungal diversity and richness of the bottom layer were significantly higher than those of the other locations (P < 0.05). The fungal diversity and richness were significantly higher in the wall of the 10-year-old cellar than the 50-year-old cellar (P < 0.05), but were significantly higher in the bottom of the 50-year-old cellar than the 10-year-old cellar (P < 0.05). A total of 21 fungal phyla and 520 genera were detected in all pit mud samples, the relative abundance of four dominant phyla (Ascomycota, Basidiomycota, Mortierellomycota and Rozellomycota) and most dominant genera such as Aspergillus and Kazachstania showed significant changes among pit ages and spatial locations (P < 0.05). Fusarium, Aspergillus, Saccharomyces and Monascus were positively correlated with the contents of water, humus, K+ and Ca2+, while Cladosporium and Vishniacozyma were positively correlated with pH. Seven nutritional modes of fungi were observed, mainly including saprophytic and pathological-saprophytic-symbiotic nutritional modes, and four single and seven mixed functional groups were determined. This study provides a theoretical basis for clarifying the structure and spatial distribution of fungal community in Jinhui Baijiu pit mud.

Angelica sinensis (Oliv.) Diels root (ASR) is a medicinal and edible traditional Chinese herb medicine. Understanding the varying efficacies in different ASR segments and their associated pharmacological mechanisms at the metabolome level has been a largely unexplored research area. This study integrates metabolomics, network pharmacology, and molecular docking to investigate the characteristics and mechanisms underlying hemostasis, blood enrichment, and blood circulation promotion in distinct ASR medicinal segments. The distinguishable metabolic spectra were visually presented for the head (ASRH), body (ASRB), and tail (ASRT) in ASR, highlighting the dominant metabolites in each. Furthermore, a network linking components, targeted proteins, signaling pathways, and diseases was constructed. The combined analysis of metabolomics and network pharmacology confirms that ASRT primarily enhances blood circulation, whereas ASRH and ASRB lean toward hemostasis and blood enrichment. The dominant ingredients of ASRT mainly influence signaling pathways of calcium, PI3K‐Akt, and arachidonic acid metabolism by modulating targeted proteins like EGFR, SRC, AKT1, and HSP90AA1, thus enhancing hemodynamics. In contrast, the dominant ingredients of ASRH and ASRB regulate PI3K‐Akt, IL‐17, and JAK‐STAT signaling pathways via proteins, such as CTNNB1, AKT1, SRC, and EP300, playing a role in hemostasis and blood enrichment. These results were subsequently validated by molecular docking. This study innovatively combines metabolomics, network pharmacology, and molecular docking to preliminarily reveal the mechanisms governing hemostasis, blood enrichment, and blood circulation improvement regulated through multiple components, targeted proteins, and pathways in different ASR segments. These findings offer valuable insights for future investigations into the efficacies of distinct ASR segments. [ABSTRACT FROM AUTHOR]

Background: Lignocellulose is a renewable and sustainable resource used to produce second-generation biofuel ethanol to cope with the resource and energy crisis. Furfural is the most toxic inhibitor of Saccharomyces cerevisiae cells produced during lignocellulose treatment, and can reduce the ability of S. cerevisiae to utilize lignocellulose, resulting in low bioethanol yield. In this study, multiple rounds of progressive ionizing radiation was combined with adaptive laboratory evolution to improve the furfural tolerance of S. cerevisiae and increase the yield of ethanol. Results: In this study, the strategy of multiple rounds of progressive X-ray radiation combined with adaptive laboratory evolution significantly improved the furfural tolerance of brewing yeast. After four rounds of experiments, four mutant strains resistant to high concentrations of furfural were obtained (SCF-R1, SCF-R2, SCF-R3, and SCF-R4), with furfural tolerance concentrations of 4.0, 4.2, 4.4, and 4.5 g/L, respectively. Among them, the mutant strain SCF-R4 obtained in the fourth round of radiation had a cellular malondialdehyde content of 49.11 nmol/mg after 3 h of furfural stress, a weakening trend in mitochondrial membrane potential collapse, a decrease in accumulated reactive oxygen species, and a cell death rate of 12.60%, showing better cell membrane integrity, stable mitochondrial function, and an improved ability to limit reactive oxygen species production compared to the other mutant strains and the wild-type strain. In a fermentation medium containing 3.5 g/L furfural, the growth lag phase of the SCF-R4 mutant strain was shortened, and its growth ability significantly improved. After 96 h of fermentation, the ethanol production of the mutant strain SCF-R4 was 1.86 times that of the wild-type, indicating that with an increase in the number of irradiation rounds, the furfural tolerance of the mutant strain SCF-R4 was effectively enhanced. In addition, through genome-transcriptome analysis, potential sites related to furfural detoxification were identified, including GAL7, MAE1, PDC6, HXT1, AUS1, and TPK3. Conclusions: These results indicate that multiple rounds of progressive X-ray radiation combined with adaptive laboratory evolution is an effective mutagenic strategy for obtaining furfural-tolerant mutants and that it has the potential to tap genes related to the furfural detoxification mechanism. Highlights: Multi-round progressive X-ray radiation combined ALE bred furfural-resistant mutants Mutants obtained through four rounds of radiation exhibited higher resistance to furfural Membrane integrity, stable mitochondrial function, and antioxidant capacity, played an important role in resisting furfural stress Multi-omics analysis identified many potential mutational sites that enhance the strain's furfural tolerance [ABSTRACT FROM AUTHOR]

Heavy-ion beam irradiation (HIBI) is useful for generating new germplasm in plants and microorganisms due to its ability to induce high mutagenesis rate, broad mutagenesis spectrum, and excellent stability of mutants. However, due to the random mutagenesis and associated mutant breeding modalities, it is imperative to improve HIBI-based mutant breeding efficiency and quality. This review discusses and summarizes the findings of existing theoretical and technical studies and presents a set of tandem strategies to enable efficient and high-quality HIBI-based mutant breeding practices. These strategies: adjust the mutation-inducing techniques, regulate cellular response states, formulate high-throughput screening schemes, and apply the generated superior genetic elements to genetic engineering approaches, thereby, improving the implications and expanding the scope of HIBI-based mutant breeding. These strategies aim to improve the mutagenesis rate, screening efficiency, and utilization of positive mutations. Here, we propose a model based on the integration of these strategies that would leverage the advantages of HIBI while compensating for its present shortcomings. Owing to the unique advantages of HIBI in creating high-quality genetic resources, we believe this review will contribute toward improving HIBI-based breeding. [ABSTRACT FROM AUTHOR]

One of the fundamental techniques in genetic engineering is the creation of Escherichia coli competent cells using the CaCl2 method. However, little is known about the mechanism of E. coli competence formation. We have previously found that the cspA gene may play an indispensable role in the preparation of E. coli DH5α competent cells through multiomics analysis. In the present study, the cellular localization, physicochemical properties, and function of the protein expressed by the cspA gene were analyzed. To investigate the role of the cspA gene in E. coli transformation, cspA‐deficient mutant was constructed by red homologous recombination. The growth, transformation efficiency, and cell morphology of the cspA‐deficient strain and E. coli were compared. It was found that there were no noticeable differences in growth and morphology between E. coli and the cspA‐deficient strain cultured at 37°C, but the mutant exhibited increased transformation efficiencies compared to E. coli DH5α for plasmids pUC19, pET‐32a, and p1304, with enhancements of 2.23, 2.24, and 3.46 times, respectively. It was proved that cspA gene is an important negative regulatory gene in the CaCl2 preparation of competent cells. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of glioma has advanced since the release of the WHO 2021 classification with more molecular alterations involved in the integrated diagnostic pathways. Our study aimed to present our experience with the clinical features and management of astrocytoma, IDH mutant based on the latest WHO classification. Methods: Patients diagnosed with astrocytoma, IDH‐mutant based on the WHO 5th edition classification of CNS tumors at our center from January 2009 to January 2022 were included. Patients were divided into WHO 2–3 grade group and WHO 4 grade group. Integrate diagnoses were retrospectively confirmed according to WHO 2016 and 2021 classification. Clinical and MRI characteristics were reviewed, and survival analysis was performed. Results: A total of 60 patients were enrolled. 21.67% (13/60) of all patients changed tumor grade from WHO 4th edition classification to WHO 5th edition. Of these, 21.43% (6/28) of grade II astrocytoma and 58.33% (7/12) of grade III astrocytoma according to WHO 4th edition classification changed to grade 4 according to WHO 5th edition classification. Sex (p = 0.042), recurrent glioma (p = 0.006), and Ki‐67 index (p < 0.001) of pathological examination were statistically different in the WHO grade 2–3 group (n = 27) and WHO grade 4 group (n = 33). CDK6 (p = 0.004), FGFR2 (p = 0.003), and MYC (p = 0.004) alterations showed an enrichment in the WHO grade 4 group. Patients with higher grade showed shorter mOS (mOS = 75.9 m, 53.6 m, 26.4 m for grade 2, 3, and 4, respectively, p = 0.01). Conclusions: Patients diagnosed as WHO grade 4 according to the 5th edition WHO classification based on molecular alterations are more likely to have poorer prognosis. Therefore, treatment should be tailored to their individual needs. Further research is needed for the management of IDH‐mutant astrocytoma is needed in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND METHODS RESULTS CONCLUSION Betel nut chewing is a significant risk factor for oral cancer due to arecoline, its primary active component. Resveratrol, a non‐flavonoid polyphenol, possesses anti‐cancer properties. It has been shown to inhibit arecoline‐induced oral malignant cells in preliminary experiments but the underlying mechanism remains unclear. This research therefore aimed to explore the potential therapeutic targets of resveratrol in treating arecoline‐induced oral cancer.Data mining identified common targets and hub targets of resveratrol in arecoline‐induced oral cancer. Gene set variation analysis (GSVA) was used to score and validate the expression and clinical significance of these hub targets in head and neck cancer (HNC) tissues. Molecular docking analysis was conducted on the hub targets. The effect of resveratrol intervention on hub targets was verified by experiments.Sixty‐one common targets and 15 hub targets were identified. Hub targets were highly expressed in HNC and were associated with unfavorable prognoses. They played a role in HNC metastasis, epithelial‐mesenchymal transition, and invasion. Their expression also affected immune cell infiltration and correlated negatively with sensitivity to chemotherapeutic agents such as bleomycin and docetaxel. Experiments demonstrated that resveratrol down‐regulated the expression of the hub targets, inhibited their proliferation and invasion, and induced apoptosis.Resveratrol inhibits the arecoline‐induced malignant phenotype of oral epithelial cells by regulating the expression of some target genes, suggesting that resveratrol may be used not only as an adjuvant treatment for oral cancer, but also as an adjuvant for oral cancer prevention due to its low toxicity and high efficacy. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

High-energy consumption and high-emission industries contribute a lot to economic development, but their carbon emissions are also huge. In order to achieve the dual-carbon target as early as possible, it is necessary to reduce the carbon emissions of high-energy consumption and high-emission industries. This paper selected five representative factors (population, per capita gross domestic product (GDP), energy intensity, energy structure and carbon emission coefficient) and adopted the logarithmic mean divisia index (LMDI) method to decompose the driving factors of carbon emissions. Therefore, this paper uses Tapio decoupling model to analyze the decoupling relationship between the two factors with the greatest impact on carbon emissions and carbon emissions. The results show that: (i) There is a good decoupling between high-energy consumption and high-emission industries and per capita GDP, and the impact of per capita GDP on carbon emissions will gradually decrease in the future; (ii) The decoupling relationship between carbon emissions and energy intensity is poor. For some industries, the reduction of energy intensity can help reduce carbon emissions. Finally, this paper puts forward some suggestions to promote carbon emission reduction. This paper provides theoretical support for studying how to reduce carbon emissions and formulate relevant emission reduction policies in the high-energy consumption and high-emission industries. [ABSTRACT FROM AUTHOR]

Predictive markers and prognostic models are useful for the individualization of cancer treatment. In this study, we sought to identify clinical and molecular factors to predict overall survival in recurrent glioma patients receiving bevacizumab-containing regimens. A cohort of 102 patients was retrospectively collected from June 2011 to January 2022 at our institution. A nomogram was generated by Cox regression and feature selection algorithms based on 19 clinicopathological and 60 molecular variables. The model's performance was internally evaluated by bootstrapping in terms of discrimination and calibration. The median overall survival from the initiation of bevacizumab administration to death or last follow-up was 11.6 months (95% CI: 9.2–13.8 months) for all 102 patients, 10.2 months (95% CI: 6.4–13.3 months) for 66 patients with grade 4 tumors, and 13.8 months (lower limit of 95% CI: 11.5 months) for 36 patients with tumors of grade lower or not available. In the final model, a lower WHO 2021 grade (Grade lower or not available vs. Grade 4, HR: 0.398, 95% CI: 0.223–0.708, p = 0.00172), having received adjuvant radiochemotherapy (Yes vs. No, HR: 0.488, 95% CI: 0.268–0.888, p = 0.0189), and wildtype EGFR (Wildtype vs. Altered, HR: 0.193, 95% CI: 0.0506–0.733, p = 0.0157; Not available vs. Altered, HR: 0.386, 95% CI: 0.184–0.810, p = 0.0118) were significantly associated with longer overall survival in multivariate Cox regression. The overall concordance index was 0.652 (95% CI: 0.566–0.714), and the areas under the time-dependent curves for 6-, 12-, and 18-month overall survival were 0.677 (95% CI: 0.516–0.816), 0.654 (95% CI: 0.470–0.823), and 0.675 (95% CI: 0.491–0.860), respectively. A prognostic model for overall survival in recurrent glioma patients treated with bevacizumab-based therapy was established and internally validated. It could serve as a reference tool for clinicians to assess the extent the patients may benefit from bevacizumab and stratify their treatment response. [ABSTRACT FROM AUTHOR]

Backgroud: Glioblastoma multiforme (GBM) is among the most aggressive cancers, with current treatments limited in efficacy. A significant hurdle in the treatment of GBM is the resistance to the chemotherapeutic agent temozolomide (TMZ). The methylation status of the MGMT promoter has been implicated as a critical biomarker of response to TMZ. Methods: To explore the mechanisms underlying resistance, we developed two TMZ‐resistant GBM cell lines through a gradual increase in TMZ exposure. Transcriptome sequencing of TMZ‐resistant cell lines revealed that alterations in histone post‐translational modifications might be instrumental in conferring TMZ resistance. Subsequently, multi‐omics analysis suggests a strong association between histone H3 lysine 9 acetylation (H3K9ac) levels and TMZ resistance. Results: We observed a significant correlation between the expression of H3K9ac and MGMT, particularly in the unmethylated MGMT promoter samples. More importantly, our findings suggest that H3K9ac may enhance MGMT transcription by facilitating the recruitment of the SP1 transcription factor to the MGMT transcription factor binding site. Additionally, by analyzing single‐cell transcriptomics data from matched primary and recurrent GBM tumors treated with TMZ, we modeled the molecular shifts occurring upon tumor recurrence. We also noted a reduction in tumor stem cell characteristics, accompanied by an increase in H3K9ac, SP1, and MGMT levels, underscoring the potential role of H3K9ac in tumor relapse following TMZ therapy. Conclusions: The increase in H3K9ac appears to enhance the recruitment of the transcription factor SP1 to its binding sites within the MGMT locus, consequently upregulating MGMT expression and driving TMZ resistance in GBM. [ABSTRACT FROM AUTHOR]

Introduction: Chronic exposure to excessive endogenous cortisol leads to brain changes in Cushing's disease (CD). However, it remains unclear how CD affects large-scale functional networks (FNs) and whether these effects are reversible after treatment. This study aimed to investigate functional network changes of CD patients and their reversibility in a longitudinal cohort. Methods: Active CD patients (N = 37) were treated by transsphenoidal pituitary surgery and reexamined 3 months later. FNs were computed from resting-state fMRI data of the CD patients and matched normal controls (NCs, N = 37). A pattern classifier was built on the FNs to distinguish active CD patients from controls and applied to FNs of the CD patients at the 3-month follow-up. Two subgroups of endocrine-remitted CD patients were identified according to their classification scores, referred to as image-based phenotypically (IBP) recovered and unrecovered CD patients, respectively. The informative FNs identified by the classification model were compared between NCs, active CD patients, and endocrine-remitted patients as well as between IBP recovered and unrecovered CD patients to explore their functional network reversibility. Results: All 37 CD patients reached endocrine remission after treatment. The classification model identified three informative FNs, including cerebellar network (CerebN), fronto-parietal network (FPN), and default mode network. Among them, CerebN and FPN partially recovered toward normal at 3 months after treatment. Moreover, the informative FNs were correlated with 24-h urinary-free cortisol and emotion scales in CD patients. Conclusion: These findings suggest that CD patients have aberrant FNs that are partially reversible toward normal after treatment. [ABSTRACT FROM AUTHOR]

The molecular mechanisms controlling organ size during plant development ultimately influence crop yield. However, a deep understanding of these mechanisms is still lacking. UBIQUITIN-SPECIFIC PROTEASE14 (UBP14), encoded by DA3, is an essential factor determining organ size in Arabidopsis (Arabidopsis thaliana). Here, we identified two suppressors of the da3-1 mutant phenotype, namely SUPPRESSOR OF da3-1 1 and 2 (SUD1 and SUD2), which encode the E3 ligases MOS4-ASSOCIATED COMPLEX 3A (MAC3A) and MAC3B, respectively. The mac3a-1 and mac3b-1 mutations partially suppressed the high ploidy level and organ size phenotypes observed in the da3-1 mutant. Biochemical analysis showed that MAC3A and MAC3B physically interacted with and ubiquitinated UBP14/DA3 to modulate its stability. We previously reported that UBP14/DA3 acts upstream of the B-type cyclin-dependent kinase CDKB1;1 and maintains its stability to inhibit endoreduplication and cell growth. In this work, MAC3A and MAC3B were found to promote the degradation of CDKB1;1 by ubiquitinating UBP14/DA3. Genetic analysis suggests that MAC3A and MAC3B act in a common pathway with UBP14/DA3 to control endoreduplication and organ size. Thus, our findings define a regulatory module, MAC3A/MAC3B-UBP14-CDKB1;1, that plays a critical role in determining organ size and endoreduplication in Arabidopsis. Analysis of 2 suppressors uncovers the molecular and genetic mechanisms by which E3 ligases MAC3A and MAC3B affect the stability of UBIQUITIN-SPECIFIC PROTEASE14 to control plant organ size. [ABSTRACT FROM AUTHOR]

Moiré superlattices, induced by an angular mismatch in layered materials provide a new index of freedom to manipulate the correlated electron states and many‐body properties of excitons. Here, trilayer MoS2 homostructures with the 3R configuration between the middle (M) and the bottom (B) layer and the top‐to‐middle (T‐M) interlayer twists ranging from 10° to 40° are fabricated via NaCl‐assisted chemical vapor deposition. The twist‐dependent interlayer interactions are systematically investigated by polarized low frequency (PLF) and high frequency (HF) Raman spectroscopy. PLF Raman results show that the energy shift in the shear mode, the breathing modes of LB31 and LB32 is respectively the much in 14°‐ and 28°‐T‐M twisted trilayer, among as‐prepared trilayer MoS2 homostructures. Moreover, the T‐M twist further affects the optical properties of the twisted MoS2 trilayer, evidenced by the photoluminescence (PL) spectroscopy. Moiré excitons are enhanced in the top‐layer twisted MoS2 trilayer with a T‐M twists of 28°, which may originate from the interlayer exciton trapped by the periodical moiré potential. The present work demonstrates that the trilayer homostructures tuned by interlayer twists can be an ideal system to tune the energy band structures and exciton properties for their potential applications in the nano‐optical electronics. [ABSTRACT FROM AUTHOR]

Background: With the significant shift in the classification, risk stratification, and standards of care for gliomas, we sought to understand how the overall survival of patients with these tumors is impacted by molecular features, clinical metrics, and treatment received., Methods: We assembled a cohort of patients with a histopathologically diagnosed glioma from The Cancer Genome Atlas, Project Genomics Evidence Neoplasia Information Exchange, and Dana-Farber Cancer Institute/Brigham and Women's Hospital. This incorporated retrospective clinical, histological, and molecular data alongside prospective assessment of patient survival., Results: 4,400 gliomas were identified: 2,195 glioblastoma, 1,198 IDH1/2-mutant astrocytoma, 531 oligodendroglioma, 271 other IDH1/2-wildtype glioma, and 205 pediatric-type glioma. Molecular classification updated 27.2% of gliomas from their original histopathologic diagnosis. Examining the distribution of molecular alterations across glioma subtypes revealed mutually exclusive alterations within tumorigenic pathways. Non-TCGA patients had significantly improved overall survival compared to TCGA patients, with 26.7%, 55.6%, and 127.8% longer survival for glioblastoma, IDH1/2-mutant astrocytoma, and oligodendroglioma respectively (all p<0.01). Several prognostic features were characterized, including NF1 alteration and 21q loss in glioblastoma, and EGFR amplification and 22q loss in IDH1/2-mutant astrocytoma. Leveraging the size of this cohort, nomograms were generated to assess the probability of overall survival based on patient age, the molecular features of a tumor, and the treatment received., Conclusions: By applying modern molecular criteria, we characterize the genomic diversity across glioma subtypes, identify clinically applicable prognostic features, and provide a contemporary update on patient survival to serve as a reference for ongoing investigations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Myocardial infarction (MI) is one of the leading causes of death. This is attributed to the dramatic changes in the myocardial microenvironment post-MI. Therefore, effective intervention in the early stages of MI is significant for inhibiting its progression and improving cardiac function. Herein, an injectable composite hydrogel scaffold (Gel-pBP@Mg) was developed by integrating magnesium (Mg)-modified black phosphorus nanosheets (pBP@Mg) into a reactive oxygen species-responsive hydrogel (Gel). This loose and porous Gel provides a natural platform for carrying pBP@Mg. In situ, sustained release of pBP@Mg is achieved via responsive ROS degradation in the infarct site. The high ROS reactivity of Black phosphorus nanosheets (BPNSs) can effectively inhibit the progression of oxidative stress in the infarct area and reduce inflammatory response by down-regulating the NF-κB pathway. Additionally, the sustained release of Mg loaded on the surface of BPNSs can effectively promote angiogenesis in MI, which is significant for the long-term prognosis after infarction. Our developed Gel-pBP@Mg effectively blocked infarction progression and improved myocardial function by sustainably inhibiting the "oxidative stress-inflammation" reaction chain and pro-angiogenesis. This study reveals Gel-pBP@Mg composite therapeutic potential in treating MI through In vitro and In vivo studies, providing a promising modality for MI treatment., (© 2024. The Author(s).)

Purpose: To examine the effects of serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) on choroidal structures with different blood glucose levels in patients with diabetes mellitus (DM) with acromegaly without diabetic retinopathy., Methods: Eighty-eight eyes of 44 patients with acromegaly were divided into a nondiabetic group (23 patients, 46 eyes) and a diabetic group (21 patients, 42 eyes). Forty-four age- and sex-matched healthy controls and 21 patients with type 2 DM without diabetic retinopathy were also included. Linear regression models with a simple slope analysis were used to identify the correlation and interaction between endocrine parameters and choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascular index (CVI)., Results: Our study revealed significant increases in the ChT, LA, SA, and TCA in patients with acromegaly compared with healthy controls, with no difference in the CVI. Comparatively, patients with DM with acromegaly had greater ChT than matched patients with type 2 DM, with no significant differences in other choroidal parameters. The enhancement of SA, LA and TCA caused by an acromegalic status disappeared in patients with diabetic status, whereas ChT and CVI were not affected by the interaction. In the diabetic acromegaly, higher IGF-1 (P = 0.006) and GH levels (P = 0.049), longer DM duration (P = 0.007), lower blood glucose (P = 0.001), and the interaction between GH and blood glucose were associated independently with thicker ChT. Higher GH levels (P = 0.016, 0.004 and 0.007), longer DM duration (P = 0.022, 0.013 and 0.013), lower blood glucose (P = 0.034, 0.011 and 0.01), and the interaction of IGF-1 and blood glucose were associated independently with larger SA, LA, and TCA. As blood glucose levels increased, the positive correlation between serum GH level and ChT diminished, and became insignificant when blood glucose was more than 7.35 mM/L. The associations between serum IGF-1 levels and LA, SA, and TCA became increasingly negative, with LA, becoming significantly and negatively associated to the GH levels only when blood glucose levels were more than 8.59 mM/L., Conclusions: Acromegaly-related choroidal enhancements diminish in the presence of DM. In diabetic acromegaly, blood glucose levels are linked negatively with changes in choroidal metrics and their association with GH and IGF-1., Translational Relevance: We revealed the potential beneficial impacts of IGF-1 and GH on structural measures of the choroid in patients with DM at relatively well-controlled blood glucose level, which could provide a potential treatment target for diabetic retinopathy.

Background: Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management., Methods: Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications., Results: 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p < 0.001), EGFR (hemorrhage group p = 0.003, non-hemorrhage group p = 0.001), and FGFR2 (hemorrhage group p = 0.007, non-hemorrhage group p = 0.001) was associated with shorter overall survival time in both hemorrhage and non-hemorrhage groups., Conclusions: Glioma patients with preoperative intratumoral hemorrhage had unfavorable prognoses compared to their nonhemorrhage counterparts. CDKN2B, KMT5B, and PIK3CA alterations were associated with an increased occurrence of intratumoral hemorrhage, which might be future targets for further investigation of intratumoral hemorrhage., (© 2024. The Author(s).)

Background: The modulating effects of probiotics and fecal microbiota transplantation (FMT) on gut flora and their direct antitumor effects remain unclear in dirty rats with established primary liver cancer. Materials & methods: Probiotics (VSL#3), FMT or tap water were administrated to three groups. Fresh fecal samples were collected from all groups for 16S rRNA analysis. Liver cancer tissues were collected to evaluate the tumor response. Results: Significant modulation of β-diversity (p = 0.023) was observed after FMT. VSL#3 and FMT had no inhibitory effect on tumors, but the density of Treg cells decreased (p = 0.031) in the FMT group. Conclusion: FMT is a more attractive alternative to probiotics in dirty rats with liver cancer.