Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma， and to reveal the change law of its material basis. MethodsHigh performance liquid chromatography（HPLC） was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces， and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside， chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics， the contents and quantity ratio relationships of the glycosides， aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed， and the partial least squares-discriminant analysis（PLS-DA） and cluster analysis of the main components in different steaming times were conducted， the statistically significant differential markers were selected with the variable importance in the projection（VIP） value>1. ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma， there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times， the anthraquinone glycosides and aglycones could be roughly divided into three stages， including rapid change stage， fluctuation change stage and stable stage， and the total amount of tannins showed a decreasing trend. However， the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes， while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening， it was found that chrysophanol， emodin， chrysophanol-8-O-β-D-glucoside， rhein， physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times. ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb， which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.

OBJECTIVE: To investigate the potential mechanism by which electroacupuncture (EA) induces macrophage polarization to promote muscle satellite cell proliferation and differentiation, accelerating the repair of acute skeletal muscle injury. METHODS: Forty-two SPF-grade SD rats were randomly divided into three groups: a blank group (n=6), a model group (n=18), and an EA group (n=18). The model and EA groups established acute blunt contusion model of the right gastrocnemius muscle using a self-made striking device. From day 1 after modeling, rats in the EA group received EA at "Chengshan" (BL57) and "Yanglingquan" (GB34) on the right side, using disperse-dense wave with a frequency of 2 Hz/100 Hz and a current of approximately 2 mA. The EA treatment was administered once daily for 30 minutes for 3, 7, or 14 days based on the designated sampling time points. Gait analysis was performed using the Cat Walk XT^TM system. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in the gastrocnemius muscle. Masson staining was applied to evaluate collagen fiber content. Immunofluorescence was used to detect the expression of proliferating cell nuclear antigen (PCNA) in muscle satellite cells. Immunohistochemistry was used to assess the expression levels of CD68 and CD206, markers of macrophages. Serum levels of pro-inflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokines (IL-10, IL-13) were detected using ELISA. RESULTS: Compared with the blank group, the model group showed a significant reduction in average movement speed on days 3 and 7 after modeling (P<0.05), and a decrease in the right hind limb stride length on day 3 (P<0.05). Compared with the model group, the EA group showed increased average movement speed and right hind limb stride length on day 7 (P<0.05). In the blank group, the gastrocnemius muscle on the right side showed uniform and consistent inter-fiber spacing, with neatly and regularly arranged muscle cells. In contrast, the model group exhibited enlarged inter-fiber spacing, edema, and significant infiltration of red blood cells and inflammatory cells, with progressively increasing fibrosis over time. By day 14 after modeling, the EA group showed a return to baseline levels of inflammatory cell infiltration, and the degree of fibrosis was significantly lower than that observed in the model group. Compared with the blank group, the ratio of collagen fibers in the gastrocnemius muscle of the model group increased significantly on days 3, 7, and 14 after modeling (P<0.05). Compared with the model group, the EA group exhibited a lower collagen fiber ratio on days 3, 7, and 14 (P<0.05). Compared with the blank group, PCNA positive expression in the gastrocnemius muscle of the model group was significantly increased on days 3, 7, and 14 after modeling (P<0.05). Compared with the model group, the EA group exhibited significantly higher PCNA positive expression on days 3 and 7 (P<0.05). Compared with the blank group, the model group showed a significant increase in CD68-positive macrophage expression in the gastrocnemius muscle on day 3 after modeling (P<0.05), while CD206-positive macrophage expression increased on days 3, 7, and 14 (P<0.05). Compared with the model group, CD68 expression was significantly lower in the EA group on day 3 (P<0.05), whereas CD206 expression was significantly higher on days 3 and 7 (P<0.05), peaking on day 7 with CD206 expression. Compared with the blank group, serum TNF-α levels were significantly elevated in the model group on days 3 and 7 after modeling (P<0.05), while serum IL-1β levels were increased on days 3, 7, and 14 (P<0.05). Serum IL-10 and IL-13 levels were significantly higher on day 7 after modeling (P<0.05). Compared with the model group, the EA group exhibited lower serum TNF-α level on day 3 (P<0.05) and reduced serum IL-1β levels on days 3 and 7 (P<0.05), while serum IL-10 and IL-13 levels were significantly increased on day 7 (P<0.05). CONCLUSION EA could promote the repair of acute blunt contusion-induced gastrocnemius muscle injury by regulating the proliferation and differentiation of muscle satellite cells. This process is closely related to macrophage polarization.
Animals ; Electroacupuncture ; Rats, Sprague-Dawley ; Rats ; Macrophages/immunology* ; Muscle, Skeletal/immunology* ; Male ; Humans ; Female ; Tumor Necrosis Factor-alpha/immunology* ; Cell Proliferation

The pathogenesis of chronic sinusitis is complex, involving a variety of inflammatory cells and inflammatory mediators, and neutrophils play a key role in the pathological process of chronic sinusitis. Understanding the molecular basis of the pathogenesis of CRS is helpful for the precise diagnosis and treatment of chronic sinusitis. This article will systematically review the mechanism of neutrophils in the inflammatory response of the body, their role in the pathogenesis and treatment progress in CRS, and look forward to future research directions.
Humans ; Neutrophils ; Sinusitis/immunology* ; Chronic Disease

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

OBJECTIVES: To explore the effect of A. muciniphila gavage on intestinal microbiota and gut-brain interaction disorders (DGBIs) in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder (HAND). METHODS: Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-, 9-, and 12-month-old wild-type (WT) mice and gp120tg transgenic mice. The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage (2×10⁸ CFU/mouse) for 6 weeks. After the treatment, immunohistochemistry, ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins, MBP and IL-1β, eosinophil infiltration, serum lipopolysaccharide (LPS) levels, and colonic expressions of occludin, ZO-1, IL-10, TNF-α and INF-γ mRNA. Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice. RESULTS: Compared with WT mice, the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus, increased serum LPS levels and decreased colonic expression of glycosylated mucin. A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight. The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β, INF-γ and IL-1β levels and obviously lowered IL-10 level; all these changes were significantly mitigated by A.muciniphila gavage, which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice. CONCLUSIONS The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice. The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes, and A. muciniphila gavage can reduce intestinal barrier injury, colonic inflammation and eosinophil activation, cognitive impairment and brain neuron injury in these mice.
Animals ; Mice, Transgenic ; Gastrointestinal Microbiome ; Mice ; Brain ; HIV Envelope Protein gp120/genetics* ; Akkermansia ; Disease Models, Animal

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Geminiviruses cause substantial crop yield losses worldwide. The replication initiator protein (Rep) encoded by geminiviruses is indispensable for geminiviral replication. The Rep protein encoded by beet severe curly top virus (BSCTV, genus Curtovirus, family Geminiviridae) induces VARIANT IN METHYLATION 5 (VIM5) expression in Arabidopsis leaves upon BSCTV infection. VIM5 functions as a ubiquitination-related E3 ligase to promote the proteasomal degradation of methyltransferases, resulting in reduction of methylation levels in the BSCTV C2-3 promoter. However, the specific domains of Rep responsible for VIM5 induction remain poorly characterized. Although Rep proteins from several geminiviruses act as viral suppressors of RNA silencing (VSRs), whether BSCTV Rep also possesses VSR activity remains to be illustrated. In this study, we employed a transient expression system in the 16c-GFP transgenic and the wild-type Nicotiana benthamiana plants to analyze the VSR and the VIM5-inducing activities of different truncated Rep proteins haboring distinct domains. We found that the N-terminal domain (amino acids 1-180) of Rep suppressed GFP silencing in 16c-GFP transgenic N. benthamiana leaves. The minimal N-terminal fragment (amino acids 1-104) induced VIM5 expression upon co-infiltration, while C-terminal truncations lacked VIM5-inducing activity. Our results indicate that the N-terminal domain of Rep encoded by BSCTV mediates the suppression of RNA silencing and induces VIM5 expression. Thus, our findings contribute to a better understanding of interactions between geminiviral Rep and plant hosts.
Geminiviridae/genetics* ; Nicotiana/metabolism* ; Arabidopsis/metabolism* ; RNA Interference ; Viral Proteins/metabolism* ; Arabidopsis Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Protein Domains ; Plant Diseases/virology* ; Methyltransferases/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; DNA Helicases/genetics*

ObjectiveTo reveal the influence of Jianchangbang characteristic processing method on the change process of volatile components and the processing mechanism of reducing toxicity and increasing efficiency of Magnoliae Officinalis Cortex（MOC） by studying the changes in the composition and content of volatile components during the processing of ginger processed Xingpo pieces. MethodSamples of raw products， ginger juice moisturized products and stir-fried and heap moisturized products of MOC were taken according to the set time points， and headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to determine the contents of volatile components in the samples， and the relative content of each component was obtained by peak area normalization. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on the sample data using SIMCA 14.1 software， and the differential components during the processing were screened with variable importance in the projection（VIP） value>1 as the indicator. ResultA total of 68 volatile components were identified in the samples， among which some of the chemical components with similar structures showed similar trends of changes， and there was also the phenomenon of interconversion between compounds. Compared with the raw products， the contents of 42 components in ginger juice moisturized products increased， while the contents of 25 components decreased， 19 components were unique， and 4 components were unique to the raw products. Compared with ginger juice moisturized products， MOC in the early stage of piling had three unique components， and the contents of 11 components such as cyclosativene and （+）-α-pinene increased， and the contents of 5 components such as tricyclic terpene and α-curcumene decreased， and ginger juice moisturized products had four unique components. Compared with the early stage of piling， in the later stage， the contents of 8 components such as （+）-α-pinene and camphene significantly increased， while the contents of 6 components such as linalool and α-selinene significantly decreased. During the processing of MOC， there were significant changes in the chemical composition of the samples before and after 20 days. The differences between ginger juice moistening and the early stage of piling， the early stage and the later stage of piling could be clearly distinguished. ConclusionDuring the preparation process of ginger processed Xingpo pieces， the addition of ginger juice can reduce the contents of stimulating components， and the contents of active components continue to increase in several stages， such as the addition of ginger juice， frying and heap moisturizing， the quality of the decoction pieces may change significantly at about 20 d of processing. This study can provide a research basis for exploring the processing mechanism of ginger processed Xingpo pieces.