Sishen Pill and its active phytochemicals in treating inflammatory bowel disease and colon cancer: an overview.

The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects. Common mechanisms in treating IBD and colon cancer mainly include regulating inflammation-related signaling pathways such as nuclear factor-kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, NOD-like receptor heat protein domain-related protein 3, and wingless-type MMTV integration site family; NF-E2-related factor 2 and hypoxia-inducible factor 1α to inhibit oxidative stress; mitochondrial autophagy and endoplasmic reticulum stress; intestinal immune cell differentiation and function through the Janus kinase/signal transducer and activator of transcription pathway; and improving the gut microbiota and intestinal barrier. Overall, existing evidence suggests the potential of the Sishen pill to improve IBD and suppress inflammation-to-cancer transformation. However, large-scale randomized controlled clinical studies and research on the safety of these clinical applications are urgently required.

Natural Biomolecule Ovomucin-Chitosan Oligosaccharide Self-Assembly Nanogel for Lutein Application Enhancement: Characterization, Environmental Stability and Bioavailability.

As an essential nutrient, lutein (LUT) has the ability to aid in the prevention of eye diseases, cardiovascular diseases, and cancer. However, the application of LUT is largely restricted by its poor solubility and susceptibility to oxidative degradation. Thus, in this study, LUT-loaded nanogel (OVM-COS-LUT) was prepared by a self-assembly of ovomucin (OVM) and chitosan oligosaccharide (COS) to enhance the effective protection and bioavailability of LUT. The nanogel had excellent dispersion (PDI = 0.25) and an 89.96% LUT encapsulation rate. XRD crystal structure analysis confirmed that the encapsulated LUT maintained an amorphous morphology. In addition, the nanogel showed satisfactory stability with pH levels ranging from 2 to 9 and high ionic strengths (>100 mM). Even under long-term storage, the nanogel maintained an optimistic stabilization and protection capacity; its effective retention rates could reach 96.54%. In vitro, digestion simulation showed that the bioaccessibility and sustained release of OVM-COS-LUT nanogel was superior to that of free LUT. The nanogel provided significant antioxidant activity, and no significant harmful effects were detected in cytotoxicity analyses at higher concentrations. In summary, OVM-COS-LUT can be utilized as a potential safe oral and functional carrier for encapsulating LUT.

The prenatal use of agmatine prevents social behavior deficits in VPA-exposed mice by activating the ERK/CREB/BDNF signaling pathway.

BACKGROUND: According to reports, prenatal exposure to valproic acid can induce autism spectrum disorder (ASD)-like symptoms in both humans and rodents. However, the exact cause and therapeutic method of ASD is not fully understood. Agmatine (AGM) is known for its neuroprotective effects, and this study aims to explore whether giving agmatine hydrochloride before birth can prevent autism-like behaviors in mouse offspring exposed prenatally to valproic acid. METHODS: In this study, we investigated the effects of AGM prenatally on valproate (VPA)-exposed mice. We established a mouse model of ASD by prenatally administering VPA. From birth to weaning, we evaluated mouse behavior using the marble burying test, open-field test, and three-chamber social interaction test on male offspring. RESULTS: The results showed prenatal use of AGM relieved anxiety and hyperactivity behaviors as well as ameliorated sociability of VPA-exposed mice in the marble burying test, open-field test, and three-chamber social interaction test, and this protective effect might be attributed to the activation of the ERK/CREB/BDNF signaling pathway. CONCLUSION: Therefore, AGM can effectively reduce the likelihood of offspring developing autism to a certain extent when exposed to VPA during pregnancy, serving as a potential therapeutic drug.

The responses of CO2 emission to nitrogen application and earthworm addition in the soybean cropland.

The effects of nitrogen application or earthworms on soil respiration in the Huang-Huai-Hai Plain of China have received increasing attention. However, the response of soil carbon dioxide (CO2) emission to nitrogen application and earthworm addition is still unclear. A field experiment with nitrogen application frequency and earthworm addition was conducted in the Huang-Huai-Hai Plain. Results showed nitrogen application frequency had a significant effect on soil respiration, but neither earthworms nor their interaction with nitrogen application frequency were significant. Low-frequency nitrogen application (NL) significantly increased soil respiration by 25%, while high-frequency nitrogen application (NH), earthworm addition (E), earthworm and high-frequency nitrogen application (E*NH), and earthworm and low-frequency nitrogen application (E*NL) also increased soil respiration by 21%, 21%, 12%, and 11%, respectively. The main reason for the rise in soil respiration was alterations in the bacterial richness and keystone taxa (Myxococcales). The NH resulted in higher soil nitrogen levels compared to NL, but NL had the highest bacterial richness. The abundance of Corynebacteriales and Gammaproteobacteria were positively connected with the CO2 emissions, while Myxococcales, Thermoleophilia, and Verrucomicrobia were negatively correlated. Our findings indicate the ecological importance of bacterial communities in regulating the carbon cycle in the Huang-Huai-Hai Plain.

A corneal stroma circular ring captured by smartphone adaptor slit lamp camera after small incision lenticule extraction.

A corneal stroma circular ring has captured by smartphone adaptor slit lamp camera after smile for 1 week.

TTSBBC: triplex target site biomarkers and barcodes in cancer.

The technology of triplex-forming oligonucleotides (TFOs) provides an approach to manipulate genes at the DNA level. TFOs bind to specific sites on genomic DNA, creating a unique intermolecular triple-helix DNA structure through Hoogsteen hydrogen bonding. This targeting by TFOs is site-specific and the locations TFOs bind are referred to as TFO target sites (TTS). Triplexes have been observed to selectively influence gene expression, homologous recombination, mutations, protein binding, and DNA damage. These sites typically feature a poly-purine sequence in duplex DNA, and the characteristics of these TTS sequences greatly influence the formation of the triplex. We introduce TTSBBC, a novel analysis and visualization platform designed to explore features of TTS sequences to enable users to design and validate TTSs. The web server can be freely accessed at https://kowalski-labapps.dellmed.utexas.edu/TTSBBC/.

Island-in-Sea Structured Pt3Fe Nanoparticles-in-Fe Single Atoms Loaded in Carbon Materials as Superior Electrocatalysts toward Alkaline HER and Acidic ORR.

In this work, Pt3Fe nanoparticles (Pt3Fe NPs) with the ordered internal structure and Pt-rich shells surrounded by plenty of Fe single atoms (Fe SAs) as active species (Pt3Fe NP-in-Fe SA) loaded in the carbon materials are successfully fabricated, which are abbreviated as island-in-sea structured (IISS) Pt3Fe NP-in-Fe SA catalysts. Moreover, the synergistic effect of O-bridging between Pt3Fe NPs and Fe SAs, and the ordered internal structured Pt3Fe NPs with Pt-rich shells of an optimal thickness contributes to the achievement of the local acidic environments on the surfaces of Pt3Fe NPs in the alkaline hydrogen evolution reaction (HER) and the enhancement of the desorption rate of *OH intermediate in the acidic oxygen reduction reaction (ORR). In addition, the electronic interactions between Pt3Fe NPs and dispersed Fe SAs cannot only provide efficient electrons transfer, but also prevent the aggregation and dissolution of Pt3Fe NPs. Furthermore, the overpotential and the half wave potential of the as-prepared IISS Pt3Fe NP-in-Fe SA catalysts toward the alkaline HER and toward the acidic ORR are 8 mV at a current density of 10 mA cm-2 and 0.933 V, respectively, which is 29 lower and 86 mV higher than those (37 mV and 0.847 V) of commercial Pt/C catalysts.

Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model.

Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.

Examining the Influence of Warm-Up Static and Dynamic Stretching, as well as Post-Activation Potentiation Effects, on the Acute Enhancement of Gymnastic Performance: A Systematic Review with Meta-Analysis.

The primary objective of this systematic review with meta-analysis is to methodically discern and compare the impact of diverse warm-up strategies, including both static and dynamic stretching, as well as post-activation potentiation techniques, on the immediate performance of gymnasts. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this paper evaluated studies that examined the gymnasts' performance after different warm-up strategies namely stretching (static [SS] or dynamic), vibration platforms (VP) or post-activation, in comparison to control conditions (e.g., mixed warm-up routines; no warm-up). The principal outcomes were centered on technical performance metrics (e.g., split, gymnastic jumps) and physical performance metrics (e.g., squat jump, countermovement jump, drop jump, balance, range of motion). Methodological assessments of the included studies were conducted using the Downs and Black Checklist. From the initial search across PubMed, Scopus, and the Web of Science databases, a total of 591 titles were retrieved, and 19 articles were ultimately incorporated in the analysis. The results revealed a non-significant differences (p > 0.05) between the SS condition and control conditions in squat jump performance, countermovement jump and gymnastic technical performance (e.g., split; split jump). Despite the difference in warm-up strategies and outcomes analyzed, the results suggest that there is no significant impairment of lower-limb power after SS. Additionally, technical elements dependent on flexibility appear to be enhanced by SS. Conversely, dynamic stretching and VP seem to be more effective for augmenting power-related and dynamic performance in gymnasts.

Supervised Offseason Training Programs are able to mitigate the Effects of Detraining in Youth Men Soccer Players Physical Fitness: A Randomized Parallel Controlled Study.

This study aimed to analyze the effects of three off-season training programs on the aerobic capacity, countermovement jump (CMJ), and linear sprint performance of young male soccer players. The study employed a randomized multi-arm design, consisting of three experimental groups: i) a high-intensity interval training (HIIT) group; (ii) a plyometric jump training (PJT) group; and (iii) a HIIT+PJT group; and an inactive control group. Fifty-eight under-19 male soccer players (aged 17.6 ±0.6 years) were randomly assigned to participate in a 3-week offseason training program exclusively performing HIIT, PJT, or a combination of both, while the fourth group remained inactive. Players underwent assessments twice, using the Yo-Yo Intermittent Recovery Test - Level 1 (YYIRT), CMJ, and 30-meter linear sprint. Significant interactions between time and groups were found in CMJ (p<0.001), YYIRT (p<0.001), and 30-m sprint (p<0.001). Group*time interaction revealed that the control group was significantly different from HIIT (p<0.001), PJT (p<0.001), and HIIT+PJT (p<0.001) considering the CMJ. Moreover, the control group was significantly different from HIIT (p=0.037) in YYIRT. Finally, the control group was significantly different from HIIT (p=0.024), PJT (p<0.001), and HIIT+PJT (p=0.021) considering the 30-m sprint. In conclusion, off-season training programs are effective in significantly reducing declines in CMJ and sprint performance compared to maintaining training cessation. However, in the YYIRT, only HIIT seems to be significantly superior to maintaining inactivity. To mitigate aerobic performance declines, incorporating HIIT sessions twice weekly during the offseason is advisable. To enhance or maintain jump performance, integrating at least one session of PJT weekly is beneficial.

Relationships between training load and body composition and physical fitness changes in sedentary individuals: A 4-month small-sided soccer games intervention.

Purpose: This study aimed to: (i) analyze the changes in physical fitness and body composition following a 4-month intervention of small-sided games (SSG) training; and (ii) analyze the association between internal and external training loads and the observed changes in physical fitness and body composition among sedentary young adults. Methods: Sixty sedentary individuals (males: 30; females: 30) participated in this randomized controlled trial study. Physical fitness and body composition parameters were assessed at the 1st, 8th weeks, and 16th weeks after a SSG intervention. Results: Significant main effects of time and gender on overall physical fitness parameters, with a notable time-group interaction were observed. For body composition measures, we found significant main effects of time, group, and gender. Furthermore, we identified significant correlations between shuttle run, handgrip, and vertical jump performance, and the time spent at VO2max (TVO2max) during SSG (r = -0.779, p = 0.001; r = -0.788, p = 0.001; r = 0.692, p = 0.004, respectively). Handgrip strength exhibited significant correlations with heat exhaustion (HE) and total distance (TD) during SSG (r = -0.616, p = 0.014; r = -0.629, p = 0.012). Similarly, we observed significant correlations between hip perimeter (HP), skinfolds (SF), waist-to-hip ratio (W:H), and TVO2max (r = 0.624, p = 0.013; r = 0.663, p = 0.007; r = 0.535, p = 0.040, respectively). Conclusion: This study indicates that the intensity achieved during SSG plays a crucial role in fostering positive adaptations in aerobic capacity, maximal strength, and jumping performance in recreational soccer. Therefore, practitioners should ensure that SSG formats generate the required stimulus to sustain prolonged periods within VO2max zones.

Effects of small-sided games training programs on physiological and physical adaptations of youth basketball players: A systematic review.

The primary objective of this study was to systematically investigate the physiological and physical fitness adaptations resulting from small-sided games (SSGs) training programs in basketball players competing at youth competitive levels, as compared to other training approaches and/or control groups. To achieve this, we conducted a literature search on PubMed, Scopus, SPORTDiscus, and Web of Science, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. From the initial 626 studies retrieved, five were considered eligible for the current study. Among the five included articles, four conducted comparisons between the effects of SSGs and running-based high-intensity interval training. Regarding this, the four studies revealed a significant improvement in the final velocity during the 30-15 Intermittent Fitness Test, ranging from 4.07% to 7.29% following SSG-based interventions. This improvement was not significantly different from the comparator group. Additionally, two studies indicated that the SSGs group showed a significant advantage in change-of-direction time, with improvements ranging from -2.11% to 6.69% after interventions, and these results were not significantly different from the comparator group. However, the effects on repeated sprint ability yielded contradictory findings; two studies reported significant improvements ranging from -5.00% to -2.16%, while two others did not show significant effects following SSGs-based interventions. Similarly, in the linear sprint, the results of SSGs-based interventions were inconsistent. In summary, based on the available research, it can be concluded that SSG-based training is effective in significantly enhancing aerobic performance and change of direction, comparable to alternative approaches. However, the effects on repeated sprint ability and sprint performance are not consistently demonstrated.

Evaluating the Effect of Deficit Irrigation on Yield and Water Use Efficiency of Drip Irrigation Cotton under Film in Xinjiang Based on Meta-Analysis.

Water scarcity constrains the sustainable development of Chinese agriculture, and deficit irrigation as a new irrigation technology can effectively alleviate the problems of water scarcity and water use inefficiency in agriculture. In this study, the drip irrigation cotton field under film in Xinjiang was taken as the research object. Meta-analysis and machine learning were used to quantitatively analyze the effects of different farm management practices, climate, and soil conditions on cotton yield and water use efficiency under deficit irrigation, to investigate the importance of the effects of different factors on cotton yield and water use efficiency, and to formulate appropriate optimization strategies. The results showed that deficit irrigation significantly increased cotton water use efficiency (7.39%) but decreased cotton yield (-15.00%) compared with full irrigation. All three deficit irrigation levels (80~100% FI, 60~80% FI, and 40~60% FI; FI: full irrigation) showed a significant decrease in cotton yield and a significant increase in water use efficiency. Under deficit irrigation, cotton yield reduction was the smallest and cotton water use efficiency increased the most when planted with one film, two tubes, a six-row cropping pattern, an irrigation frequency ≥10 times, a nitrogen application of 300~400 kg·ha-1, and a crop density ≥240,000 per hectare, and planted with the Xinluzhong series of cotton varieties; deficit irrigation in areas with average annual temperature >10 °C, annual evapotranspiration >2000 mm, annual precipitation <60 mm, and with loam, sandy soil had the least inhibition of cotton yield and the greatest increase in cotton water use efficiency. The results of the random forest showed that the irrigation amount and nitrogen application had the greatest influence on cotton yield and water use efficiency. Rational irrigation based on optimal management practices under conditions of irrigation not less than 90% FI is expected to achieve a win-win situation for both cotton yield and water use efficiency. The above results can provide the best strategy for deficit irrigation and efficient water use in drip irrigation cotton under film in arid areas.

Predictive models for perceived convenience of accessing outdoor activities among elderly with physical disabilities in rural China.

BACKGROUND: The elderly, especially those with physical disabilities, often encounter barriers that prevent them from accessing outdoor activities. Their perceptions of the convenience of accessing outdoor activities may be influenced by various factors including their health, the social context, and/or planned behavior. This study aimed to develop predictive models that identify the principal determinants of perceived convenience among this demographic, and it also examined the disparities observed between genders. METHODS: This was a cross-sectional survey of 1216 community-dwelling older people with physical disabilities in rural China. Grounded on the rehabilitation concepts and the theory of planned behavior, structural equation models integrated health and social behavior factors were constructed to predict perceived convenience of accessing outdoor activities. The standardized coefficients explained the contributions of various factors to the variance. RESULTS: The final structural models demonstrated good fit for both female and male participants. Perceptions of the convenience of accessing outdoor activities among both women and men were directly impacted by their physical functioning and their intention to participate, and indirectly by medical expenditure, subjective norms, pain, and role limitation in emotional interactions. Positive mental health was more influential for women, while men were more influenced by subjective norms. CONCLUSIONS: Structural equation models have effectively predicted the self-reported convenience of accessing outdoor activities, underscoring the importance of functional and behavioral rehabilitation. Furthermore, gender-sensitive rehabilitation programs are advised to promote engagement in outdoor activities among elderly individuals with physical disabilities.

Enhancing oncolytic virus efficiency with methionine and N-(3-aminoprolil)methacrylamide modified acrylamide cationic block polymer.

Oncolytic virus ablation of tumor cells has the advantages of high tumor selectivity, strong immunogenicity, and low side effects. However, the recognition and clearance of oncolytic viruses by the immune system are the main factors limiting their anti-tumor efficiency. As a highly biosafe and highly modifiable oncolytic virus vector, acrylamide can improve the long-term circulation of oncolytic viruses. Still, it is limited in its uptake efficiency by tumor cells. Herein, we constructed an N-hydroxymethyl acrylamide-b-(N-3-aminopropyl methacrylamide)-b-DMC block copolymer (NMA-b-APMA-b-DMA, NAD) as an oncolytic virus carrier, which not only improves the long-term circulation of oncolytic viruses in the body but also shows excellent stability for loading an oncolytic virus. The data shows that there was no obvious difference in the transfection effect of the NAD/Ad complex with or without neutralizing antibodies in the medium, which meant that the cationic carrier mediated by NAD/Ad had good serum stability. Only 10 micrograms of NAD carrier are needed to load the oncolytic virus, which can increase the transfection efficiency by 50 times. Cell experiments and mouse animal experiments show that NAD vectors can significantly enhance the anti-tumor effect of oncolytic viruses. We hope that this work will promote the application of acrylamide as an oncolytic virus vector and provide new ideas for methods to modify acrylamide for biomedical applications.

Genomic characterisation of blaNDM-5-IncX3 plasmid in an ST4 Klebsiella aerogenes clinical isolate.

OBJECTIVES: The dissemination of New Delhi metallo-ß-lactamase-5 (NDM-5) among various species of Enterobacterales has attracted serious global attention. Here, we characterise the genomic characterisation of blaNDM-5-IncX3 plasmid (pNDM-KA3) in an ST4 Klebsiella aerogenes (KA3) strain isolated from a neonate with pneumonia. METHODS: Antimicrobial susceptibility and multilocus sequence typing was performed for the KA3. The plasmid conjugation assay and plasmid stability of the KA3 (pNDM-KA3) were also analysed. The pNDM-KA3 plasmid was further analysed by whole-genome sequencing and comparative analysis to determine the genetic environment of blaNDM-5. RESULTS: The KA3 strain belongs to ST4 and shows high resistance to ß-lactam antibiotics, including carbapenems, but is susceptible to ciprofloxacin, amikacin, tigecycline, and colistin. The pNDM-KA3 was successfully transferred to the recipient E. coli J53 and showed strong stability in K. aerogenes. Genomic sequencing revealed that the pNDM-KA3 plasmid was assigned to plasmid incompatibility group X3 with 43367 bp, and a conserved structure sequence of △IS3000-△ISAba125-IS5-blaNDM-5-bleMBL- trpF-dsbC-IS26 was detected upstream and downstream of the blaNDM-5 gene. Further analysis revealed that insertion sequences mediated the dissemination of blaNDM-5 from other species of Enterobacterales. The pNDM-KA3 showed high similarity to blaNDM-5-harbouring plasmids in other species of Enterobacterales, with these plasmids carrying genes for replication (repB), partitioning (parA and parB), stability (hns), and conjugative transfer (virB and virD). CONCLUSIONS: Continued monitoring for the dissemination of blaNDM-5 among uncommon Enterobacterales species should be further reinforced.

Aberrant activated Notch1 promotes prostate enlargement driven by androgen signaling via disrupting mitochondrial function in mouse.

The prostate is a vital accessory gonad in the mammalian male reproductive system. With the ever-increasing proportion of the population over 60 years of age worldwide, the incidence of prostate diseases, such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa), is on the rise and is gradually becoming a significant medical problem globally. The notch signaling pathway is essential in regulating prostate early development. However, the potential regulatory mechanism of Notch signaling in prostatic enlargement and hyperplasia remains unclear. In this study, we proved that overactivation of Notch1 signaling in mouse prostatic epithelial cells (OEx) led to prostatic enlargement via enhancing proliferation and inhibiting apoptosis of prostatic epithelial cells. Further study showed that N1ICD/RBPJ directly up-regulated the androgen receptor (AR) and enhanced prostatic sensitivity to androgens. Hyper-proliferation was not found in orchidectomized OEx mice without androgen supply but was observed after Dihydrotestosterone (DHT) supplementation. Our data showed that the number of mitochondrion in prostatic epithelial cells of OEx mice was increased, but the mitochondrial function was impaired, and the essential activity of the mitochondrial respiratory electron transport chain was significantly weakened. Disordered mitochondrial number and metabolic function further resulted in excessive accumulation of reactive oxygen species (ROS). Importantly, anti-oxidant N-Acetyl-L-Cysteine (NAC) therapy could alleviate prostatic hyperplasia caused by the over-activation of Notch1 signaling. Furthermore, we observed the incremental Notch signaling activity in progenitor-like club cells in the scRNA-seq data set of human BPH patients. Moreover, the increased number of TROP2+ progenitors and Club cells was also confirmed in our OEx mice. In conclusion, our study revealed that over-activated Notch1 signaling induces prostatic enlargement by increasing androgen receptor sensitivity, disrupting cellular mitochondrial metabolism, increasing ROS, and a higher number of progenitor cells, all of which can be effectively rescued by NAC treatment.

MoCoLo: a testing framework for motif co-localization.

Sequence-level data offers insights into biological processes through the interaction of two or more genomic features from the same or different molecular data types. Within motifs, this interaction is often explored via the co-occurrence of feature genomic tracks using fixed-segments or analytical tests that respectively require window size determination and risk of false positives from over-simplified models. Moreover, methods for robustly examining the co-localization of genomic features, and thereby understanding their spatial interaction, have been elusive. We present a new analytical method for examining feature interaction by introducing the notion of reciprocal co-occurrence, define statistics to estimate it and hypotheses to test for it. Our approach leverages conditional motif co-occurrence events between features to infer their co-localization. Using reverse conditional probabilities and introducing a novel simulation approach that retains motif properties (e.g. length, guanine-content), our method further accounts for potential confounders in testing. As a proof-of-concept, motif co-localization (MoCoLo) confirmed the co-occurrence of histone markers in a breast cancer cell line. As a novel analysis, MoCoLo identified significant co-localization of oxidative DNA damage within non-B DNA-forming regions that significantly differed between non-B DNA structures. Altogether, these findings demonstrate the potential utility of MoCoLo for testing spatial interactions between genomic features via their co-localization.

Genomic and immune microenvironment features influencing chemoimmunotherapy response in gastric cancer with peritoneal metastasis: a retrospective cohort study.

BACKGROUND: Patients with peritoneal metastasis (PM) from gastric cancer (GC) exhibit poor prognosis. Chemoimmunotherapy offers promising clinical benefits; however, its efficacy and predictive biomarkers in a conversion therapy setting remain unclear. The authors aimed to retrospectively evaluate chemoimmunotherapy efficacy in a conversion therapy setting for GC patients with PM and establish a prediction model for assessing clinical benefits. MATERIALS AND METHODS: A retrospective evaluation of clinical outcomes encompassed 55 GC patients with PM who underwent chemoimmunotherapy in a conversion therapy setting. Baseline PM specimens were collected for genomic and transcriptomic profiling. Clinicopathological factors, gene signatures, and tumor immune microenvironment were evaluated to identify predictive markers and develop a prediction model. RESULTS: Chemoimmunotherapy achieved a 41.8% objective response rate and 72.4% R0 resection rate in GC patients with PM. Patients with conversion surgery showed better overall survival (OS) than those without the surgery (median OS: not reached vs 7.82 m, P<0.0001). Responders to chemoimmunotherapy showed higher ERBB2 and ERBB3 mutation frequencies, CTLA4 and HLA-DQB1 expression, and CD8+ T cell infiltration, but lower CDH1 mutation and naïve CD4+ T cell infiltration, compared to nonresponders. A prediction model was established integrating CDH1 and ERBB3 mutations, HLA-DQB1 expression, and naïve CD4+ T cell infiltration (AUC=0.918), which were further tested using an independent external cohort (AUC=0.785). CONCLUSION: This exploratory study comprehensively evaluated clinicopathological, genomic, and immune features and developed a novel prediction model, providing a rational basis for the selection of GC patients with PM for chemoimmunotherapy-involved conversion therapy.

SWCNTs/PEDOT:PSS nanocomposites-modified microelectrode arrays for revealing locking relations between burst and local field potential in cultured cortical networks.

Burst and local field potential (LFP) are fundamental components of brain activity, representing fast and slow rhythms, respectively. Understanding the intricate relationship between burst and LFP is crucial for deciphering the underlying mechanisms of brain dynamics. In this study, we fabricated high-performance microelectrode arrays (MEAs) using the SWCNTs/PEDOT:PSS nanocomposites, which exhibited favorable electrical properties (low impedance: 12.8 ± 2.44 kΩ) and minimal phase delay (-11.96 ± 1.64°). These MEAs enabled precise exploration of the burst-LFP interaction in cultured cortical networks. After a 14-day period of culture, we used the MEAs to monitor electrophysiological activities and revealed a time-locking relationship between burst and LFP, indicating the maturation of the neural network. To further investigate this relationship, we modulated burst firing patterns by treating the neural culture with increasing concentrations of glycine. The results indicated that glycine effectively altered burst firing patterns, with both duration and spike count increasing as the concentration rose. This was accompanied by an enhanced level of time-locking between burst and LFP but a decrease in synchrony among neurons. This study not only highlighted the pivotal role of SWCNTs/PEDOT:PSS-modified MEAs in elucidating the interaction between burst and LFP, bridging the gap between slow and fast brain rhythms in vitro but also provides valuable insights into the potential therapeutic strategies targeting neurological disorders associated with abnormal rhythm generation.