Characterizing genetic variation on the Z chromosome in Schistosoma japonicum reveals host-parasite co-evolution.

BACKGROUND: Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum is endemic to Asia; the Z chromosome of S. japonicum comprises one-quarter of the entire genome. Detection of positive selection using resequencing data to understand adaptive evolution has been applied to a variety of pathogens, including S. japonicum. However, the contribution of the Z chromosome to evolution and adaptation is often neglected. METHODS: We obtained 1,077,526 high-quality SNPs on the Z chromosome in 72 S. japonicum using re-sequencing data publicly. To examine the faster Z effect, we compared the sequence divergence of S. japonicum with two closely related species, Schistosoma haematobium and S. mansoni. Genetic diversity was compared between the Z chromosome and autosomes in S. japonicum by calculating the nucleotide diversity (π) and Dxy values. Population structure was also assessed based on PCA and structure analysis. Besides, we employed multiple methods including Tajima's D, FST, iHS, XP-EHH, and CMS to detect positive selection signals on the Z chromosome. Further RNAi knockdown experiments were performed to investigate the potential biological functions of the candidate genes. RESULTS: Our study found that the Z chromosome of S. japonicum showed faster evolution and more pronounced genetic divergence than autosomes, although the effect may be smaller than the variation among genes. Compared with autosomes, the Z chromosome in S. japonicum had a more pronounced genetic divergence of sub-populations. Notably, we identified a set of candidate genes associated with host-parasite co-evolution. In particular, LCAT exhibited significant selection signals within the Taiwan population. Further RNA interference experiments suggested that LCAT is necessary for S. japonicum survival and propagation in the definitive host. In addition, we identified several genes related to the specificity of the intermediate host in the C-M population, including Rab6 and VCP, which are involved in adaptive immune evasion to the host. CONCLUSIONS: Our study provides valuable insights into the adaptive evolution of the Z chromosome in S. japonicum and further advances our understanding of the co-evolution of this medically important parasite and its hosts.

A novel reverse perilesional home phototherapy can promote the repigmentation of vitiligo patches with complete leukotrichia: A 12-week, open-label, double-arm, multicenter, randomized clinical trial.

BACKGROUND/PURPOSE: Existing phototherapies are ineffective for treating patients with vitiligo with complete leukotrichia. We compared the efficacy of reverse perilesional irradiation, during which only the lesional areas are covered, with conventional narrowband ultraviolet B (NB-UVB) home phototherapy for repigmentation of non-segmental vitiligo in patients with complete leukotrichia. METHODS: This was a 12-week, open-label, double-arm, multicenter clinical trial, with a total of 121 patients with non-segmental vitiligo who were randomly divided into two groups (both received topical tacrolimus): the conventional NB-UVB irradiation (CI) and reverse perilesional NB-UVB irradiation (RI) groups. RESULTS: A statistically significant difference in improvement from baseline was observed in the RI group compared with the findings in the CI group (-30.8% ± 11.8% vs. -25.5% ± 11.05%, respectively [p = .010]; pair-wise comparison p = .900 at week 4, p = .104 at week 8, and p = .010 at week 12). At week 12, the average percentage change from baseline of leukotrichia in the irradiation area significantly decreased from 100% to 82.2% ± 13.65% in the RI group, and from 100% to 88.7% ± 9.64% in the CI group (p = .027). Adverse events were minor, including desquamation, dryness, erythema, and blisters. No severe or lasting side effects were observed during the study. CONCLUSION: RI mediated better repigmentation of vitiligo with complete leukotrichia than CI.

Age-adjusted Charlson comorbidity index is associated with the risk of osteoporosis in older fall-prone men: a retrospective cohort study.

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.

A rare complex structural variant of novel intragenic inversion combined with reciprocal translocation t(X;1)(p21.2;p13.3) in Duchenne muscular dystrophy.

Structural variants (SVs) are infrequently observed in Duchenne muscular dystrophy (DMD), a condition mainly marked by deletions and point mutations in the DMD gene. SVs in DMD remain difficult to reliably detect due to the limited SV-detection capacity of conventionally used short-read sequencing technology. Herein, we present a family, a boy and his mother, with clinical signs of muscular dystrophy, elevated creatinine kinase levels, and intellectual disability. A muscle biopsy from the boy showed dystrophin deficiency. Routine molecular techniques failed to detect abnormalities in the DMD gene, however, dystrophin mRNA transcripts analysis revealed an absence of exons 59 to 79. Subsequent long-read whole-genome sequencing identified a rare complex structural variant, a 77 kb novel intragenic inversion, and a balanced translocation t(X;1)(p21.2;p13.3) rearrangement within the DMD gene, expanding the genetic spectrum of dystrophinopathy. Our findings suggested that SVs should be considered in cases where conventional molecular techniques fail to identify pathogenic variants.

Prediction of ovarian cancer prognosis using statistical radiomic features of ultrasound images.

Ovarian cancer is the deadliest gynecologic malignancy worldwide. Ultrasound is the most useful non-invasive test for preoperative diagnosis of ovarian cancer. In this study, by leveraging multiple ultrasound images from the same patient to generate personalized, informative statistical radiomic features, we aimed to develop improved ultrasound image-based prognostic models for ovarian cancer. A total of 2,057 ultrasound images from 514 ovarian cancer patients, including 355 patients with epithelial ovarian cancer, from two hospitals in China were collected for this study. The models were constructed using our recently developed Frequency Appearance in Multiple Univariate pre-Screening (FAMUS) feature selection algorithm and Cox proportional hazards model. The models showed high predictive performance for overall survival (OS) and recurrence-free survival (RFS) in both epithelial and nonepithelial ovarian cancer, with concordance indices (C-index) ranging from 0.773 to 0.794. Radiomic scores predicted 2-year OS and RFS risk groups with significant survival differences (log-rank test, P<1.0e-4 for both validation cohorts). OS and RFS hazard ratios between low- and high-risk groups were 15.994 and 30.692 (internal cohort) and 19.339 and 19.760 (external cohort), respectively. The improved performance of these newly developed prognostic models was mainly attributed to the use of multiple preoperative ultrasound images from the same patient to generate statistical radiomic features, rather than simply using the largest tumor ROI among them. The models also revealed that the roundness of tumor lesion shape was positively correlated with prognosis for ovarian cancer. In summary, the newly developed prognostic models based on statistical radiomic features from ultrasound images were highly predictive of the risk of cancer-related death and possible recurrence not only for patients with epithelial ovarian cancer but also for those with nonepithelial ovarian cancer. They thereby provide reliable, non-invasive markers for individualized prognosis evaluation and clinical decision-making for patients with ovarian cancer.

Nonclassical crystallization of goethite nanorods in limpet teeth by self-assembly of silica-rich nanoparticles reveals structure-mechanical property relations.

The intricate organization of goethite nanorods within a silica-rich matrix makes limpet teeth the strongest known natural material. However, the mineralization pathway of goethite in organisms under ambient conditions remains elusive. Here, by investigating the multi-level structure of limpet teeth at different growth stages, it is revealed that the growth of goethite crystals proceeds by the attachment of amorphous nanoparticles, a nonclassical crystallization pathway widely observed during the formation of calcium-based biominerals. Importantly, these nanoparticles contain a high amount of silica, which is gradually expelled during the growth of goethite. Moreover, in mature teeth of limpet, the content of silica correlates with the size of goethite crystals, where smaller goethite crystals are densely packed in the leading part with higher content of silica. Correspondingly, the leading part exhibits higher hardness and elastic modulus. Thus, this study not only reveals the nonclassical crystallization pathway of goethite nanorods in limpet teeth, but also highlights the critical roles of silica in controlling the hierarchical structure and the mechanical properties of limpet teeth, thus providing inspirations for fabricating biomimetic materials with excellent properties.

Dimension-Confined Growth of a Crack-Free PbS Microplate Array for Infrared Image Sensing.

Epitaxy of semiconductors is a necessary step toward the development of electronic devices such as lasers, detectors, transistors, and solar cells. However, the lattice ordering of semiconductor functional films is inevitably disrupted by excessive concentrated stress due to the mismatch of the thermal expansion coefficient. Herein, combined with the first-principles calculation, we find that a rigid film/substrate bilayer heterostructure with a large thermal expansion mismatch upon cooling to room temperature from growth is free of surface cracks when the rigid film exhibits a dimension smaller than the critical condition for the breaking energy. The principle has been verified in a PbS/SrTiO3 bilayer system that is crack free on PbS single-crystalline microplate arrays through the designing of a dimension-confined growth (DCG) method. Interestingly, this crack-free, large-scale PbS microplate array exhibits exceptional uniformity in morphology, dimensions, thickness, and photodetection properties, enabling a broad-band infrared image sensing. This work provides a new perspective to design materials and arrays that demand smooth and continuous surfaces, which are not limited only to semiconductor electronics but also include mechanical structures, optical materials, biomedical materials, and others.

Multifunctional Nanocomposite Yield-Stress Fluids for Printable and Stretchable Electronics.

Compliant materials are crucial for stretchable electronics. Stretchable solids and gels have limitations in deformability and durability, whereas active liquids struggle to create complex devices. This study presents multifunctional yield-stress fluids as printable ink materials to construct stretchable electronic devices. Ionic nanocomposites comprise silica nanoparticles and ion liquids, while electrical nanocomposites use the natural oxidation of liquid metals to produce gallium oxide nanoflake additives. These nanocomposite inks can be printed on an elastomer substrate and stay in a solid state for easy encapsulation. However, their transition into a liquid state during stretching allows ultrahigh deformability up to the fracture strain of the elastomer. The ionic inks produce strain sensors with high stretchability and temperature sensors with high sensitivity of 7% °C-1. Smart gloves are further created by integrating these sensors with printed electrical interconnects, demonstrating bimodal detection of temperatures and hand gestures. The nanocomposite yield-stress fluids combine the desirable qualities of solids and liquids for stretchable devices and systems.

Notch-targeted Therapeutic in Colorectal Cancer by Notch1 Attenuation via Tumor Microenvironment-Responsive Cascade DNA Delivery.

The Notch signaling is a key molecular pathway that regulates cell fate and development. Aberrant Notch signaling can lead to carcinogenesis and progression of malignant tumors. However, current therapies targeting Notch pathway lack specificity and induce high toxicity. In this report, we design a tumor microenvironment-responsive and injectable hydrogel to load plasmid DNA complexes as a cascade gene delivery system to achieve precise Notch-targeted gene therapy of colorectal cancer (CRC). The hydrogels were prepared through cross-linking between phenylboric acid groups-containing poly(oligo(ethylene glycol)methacrylate) (POEGMA) and epigallocatechin gallate (EGCG), which were used to load the complexes between plasmid DNA encoding short hairpin RNAs of Notch1 (shNotch1) and fluorinated polyamidoamine (PAMAM-F) (PAMAM-F/shNotch1). In response to low pH and H2O2 in tumor microenvironment, the hydrogel can be dissociated and release the complexes for precise delivery of shNotch1 into tumor cells and inhibit Notch1 activity to suppress malignant biological behaviors of CRC. In the subcutaneous tumor model of CRC, PAMAM-F/shNotch1-loaded hydrogels can accurately attenuate Notch1 activity and significantly inhibit tumor growth without affecting Notch signal in adjacent normal tissues. Therefore, this therapeutic system can precisely inhibit Notch1 signal in CRC with high responsiveness and low toxicity, providing a promising Notch-targeted gene therapeutic for human malignancy. This article is protected by copyright. All rights reserved.

Pangenome characterization and analysis of the NAC gene family reveals genes for Sclerotinia sclerotiorum resistance in sunflower (Helianthus annuus).

BACKGROUND: Sunflower (Helianthus annuus) is one of the most important economic crops in oilseed production worldwide. The different cultivars exhibit variability in their resistance genes. The NAC transcription factor (TF) family plays diverse roles in plant development and stress responses. With the completion of the H. annuus genome sequence, the entire complement of genes coding for NACs has been identified. However, the reference genome of a single individual cannot cover all the genetic information of the species. RESULTS: Considering only a single reference genome to study gene families will miss many meaningful genes. A pangenome-wide survey and characterization of the NAC genes in sunflower species were conducted. In total, 139 HaNAC genes are identified, of which 114 are core and 25 are variable. Phylogenetic analysis of sunflower NAC proteins categorizes these proteins into 16 subgroups. 138 HaNACs are randomly distributed on 17 chromosomes. SNP-based haplotype analysis shows haplotype diversity of the HaNAC genes in wild accessions is richer than in landraces and modern cultivars. Ten HaNAC genes in the basal stalk rot (BSR) resistance quantitative trait loci (QTL) are found. A total of 26 HaNAC genes are differentially expressed in response to Sclerotinia head rot (SHR). A total of 137 HaNAC genes are annotated in Gene Ontology (GO) and are classified into 24 functional groups. GO functional enrichment analysis reveals that HaNAC genes are involved in various functions of the biological process. CONCLUSIONS: We identified NAC genes in H. annuus (HaNAC) on a pangenome-wide scale and analyzed S. sclerotiorum resistance-related NACs. This study provided a theoretical basis for further genomic improvement targeting resistance-related NAC genes in sunflowers.

Temporal change in multimorbidity prevalence, clustering patterns, and the association with mortality: findings from the China Kadoorie Biobank study in Jiangsu Province.

Objectives: The characteristics of multimorbidity in the Chinese population are currently unclear. We aimed to determine the temporal change in multimorbidity prevalence, clustering patterns, and the association of multimorbidity with mortality from all causes and four major chronic diseases. Methods: This study analyzed data from the China Kadoorie Biobank study performed in Wuzhong District, Jiangsu Province. A total of 53,269 participants aged 30-79 years were recruited between 2004 and 2008. New diagnoses of 15 chronic diseases and death events were collected during the mean follow-up of 10.9 years. Yule's Q cluster analysis method was used to determine the clustering patterns of multimorbidity. A Cox proportional hazards model was used to estimate the associations of multimorbidity with mortalities. Results: The overall multimorbidity prevalence rate was 21.1% at baseline and 27.7% at the end of follow-up. Multimorbidity increased more rapidly during the follow-up in individuals who had a higher risk at baseline. Three main multimorbidity patterns were identified: (i) cardiometabolic multimorbidity (diabetes, coronary heart disease, stroke, and hypertension), (ii) respiratory multimorbidity (tuberculosis, asthma, and chronic obstructive pulmonary disease), and (iii) mental, kidney and arthritis multimorbidity (neurasthenia, psychiatric disorders, chronic kidney disease, and rheumatoid arthritis). There were 3,433 deaths during the follow-up. The mortality risk increased by 24% with each additional disease [hazard ratio (HR) = 1.24, 95% confidence interval (CI) = 1.20-1.29]. Compared with those without multimorbidity at baseline, both cardiometabolic multimorbidity and respiratory multimorbidity were associated with increased mortality from all causes and four major chronic diseases. Cardiometabolic multimorbidity was additionally associated with mortality from cardiovascular diseases and diabetes, with HRs of 2.64 (95% CI = 2.19-3.19) and 28.19 (95% CI = 14.85-53.51), respectively. Respiratory multimorbidity was associated with respiratory disease mortality, with an HR of 9.76 (95% CI = 6.22-15.31). Conclusion: The prevalence of multimorbidity has increased substantially over the past decade. This study has revealed that cardiometabolic multimorbidity and respiratory multimorbidity have significantly increased mortality rates. These findings indicate the need to consider high-risk populations and to provide local evidence for intervention strategies and health management in economically developed regions.

Film mulching counteracts the adverse effects of mild moisture deficiency, and improves the quality and yield of Cyperus esculentus. L grass and tuber in the oasis area of Tarim Basin.

Introduction: Plastic film mulching (PFM) and deficit irrigation (DI) are vital water-saving approaches in arid agriculture. Cyperus esculentus is a significant crop in dry zones. However, scant data exists on the impacts of these water-saving methods on C. esculentus yield and quality. Method: Using randomized block experiment design. Three irrigation strategies were tested: CK (standard irrigation), RW20 (20% water reduction), and RW40 (40% water reduction). Mulchin treatments included film mulching (FM) and no film mulching (NFM). Results: Results revealed substantial effects of film mulching and drip irrigation on soil nutrients and physical properties, with minor influence on grass, root, and tuber stoichiometry. PF treatment, DI treatments, and their interaction significantly affected C. esculentus forage and tuber yields. Initially, grass and tuber yields increased and then decreased with reduced irrigation. The highest yields were under RW20 (3716.31 and 4758.19 kg/ha). FM increased grass and tuber yield by 17.99% and 8.46%, respectively, over NFM. The water reduction augmented the biomass distribuiton of the leaf and root, while reducing the tuber biomass in NFM. FM significantely impacted grass ether extract content, while reduced water influenced grass and tuber crude protein and tuber ether extract content. Mild water stress increased ether extract, crude protein, and soluble matter in grass and tubers, while excessive RW decreased them. Conclusion: Integrating soil traits, nutrients, yield, and quality, findings indicate C. esculentus yield and quality primarily hinge on soil water content, pond hydrogenase, and electrical conductivity. Based on this results, the recommended strategy is to reduce irrigation by 20% for cultivating C. esculentus in this area.

Curcumin Inhibits α-Synuclein Aggregation by Acting on Liquid-Liquid Phase Transition.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is linked to α-synuclein (α-Syn) aggregation. Despite no specific drug being available for its treatment, curcumin, from the spice turmeric, shows promise. However, its application in PD is limited by a lack of understanding of its anti-amyloidogenic mechanisms. In this study, we first reconstructed the liquid-liquid phase separation (LLPS) of α-Syn in vitro under different conditions, which may be an initial step in entraining the pathogenic aggregation. Subsequently, we evaluated the effects of curcumin on the formation of droplets, oligomers, and aggregated fibers during the LLPS of α-synuclein, as well as its impact on the toxicity of aggregated α-synuclein to cultured cells. Importantly, we found that curcumin can inhibit amyloid formation by inhibiting the occurrence of LLPS and the subsequent formation of oligomers of α-Syn in the early stages of aggregation. Finally, the molecular dynamic simulations of interactions between α-Syn decamer fibrils and curcumin showed that van der Waal's interactions make the largest contribution to the anti-aggregation effect of curcumin. These results may help to clarify the mechanism by which curcumin inhibits the formation of α-Syn aggregates during the development of PD.

An Intelligent Thermal Compensation System Using Edge Computing for Machine Tools.

This paper focuses on the use of smart manufacturing in lathe-cutting tool machines, which can experience thermal deformation during long-term processing, leading to displacement errors in the cutting head and damage to the final product. This study uses time-series thermal compensation to develop a predictive system for thermal displacement in machine tools, which is applicable in the industry using edge computing technology. Two experiments were carried out to optimize the temperature prediction models and predict the displacement of five axes at the temperature points. First, an examination is conducted to determine possible variances in time-series data. This analysis is based on the data obtained for the changes in time, speed, torque, and temperature at various locations of the machine tool. Using the viable machine-learning models determined, the study then examines various cutting settings, temperature points, and machine speeds to forecast the future five-axis displacement. Second, to verify the precision of the models created in the initial phase, other time-series models are examined and trained in the subsequent phase, and their effectiveness is compared to the models acquired in the first phase. This work also included training seven models of WNN, LSTNet, TPA-LSTM, XGBoost, BiLSTM, CNN, and GA-LSTM. The study found that the GA-LSTM model outperforms the other three best models of the LSTM, GRU, and XGBoost models with an average precision greater than 90%. Based on the analysis of training time and model precision, the study concluded that a system using LSTM, GRU, and XGBoost should be designed and applied for thermal compensation using edge devices such as the Raspberry Pi.

Genome-wide identification of JAZ gene family in sugarcane and function analysis of ScJAZ1/2 in drought stress response and flowering regulation.

The JASMONATE ZIM DOMAIN (JAZ) proteins are a key inhibitors of the jasmonic acid (JA) signaling pathway that play an important role in the regulation of plant growth and development and environmental stress responses. However, there is no systematic identification and functional analysis of JAZ gene family members in sugarcane. In this study, a total of 49 SsJAZ genes were identified from the wild sugarcane species Saccharum spontaneum genome that were unevenly distributed on 13 chromosomes. Phylogenetic analysis showed that all SsJAZ members can be divided into six groups, and most of the SsJAZ genes contained photoreactive and ABA-responsive elements. RNA-seq analysis revealed that SsJAZ1-1/2/3/4 and SsJAZ7-1 were significantly upregulated under drought stress. The transcript level of ScJAZ1 which is the homologous gene of SsJAZ1 in modern sugarcane cultivars was upregulated by JA, PEG, and abscisic acid (ABA). Moreover, ScJAZ1 can interact with three other JAZ proteins to form heterodimers. The spatial and temporal expression analysis showed that SsJAZ2-1/2/3/4 were highly expressed in different tissues and growth stages and during the day-night rhythm between 10:00 and 18:00. Overexpression of ScJAZ2 in Arabidopsis accelerated flowering through activating the expression of AtSOC1, AtFT, and AtLFY. Moreover, the transcription level of ScJAZ2 was about 30-fold in the early-flowering sugarcane variety than that of the non-flowering variety, indicating ScJAZ2 positively regulated flowering. This first systematic analysis of the JAZ gene family and function analysis of ScJAZ1/2 in sugarcane provide key candidate genes and lay the foundation for sugarcane breeding.

The long-term outcomes and safety of severe aplastic anemia treated with porcine antilymphocyte globulin plus cyclosporine, with or without thrombopoietin receptor agonists: a double-center retrospective study.

BACKGROUND: Porcine antilymphocyte globulin (p-ALG) combined with cyclosporine (CsA) has been commonly used for severe aplastic anemia (SAA) patients, but few studies on the combination of p-ALG and thrombopoietin receptor agonist (TPO-RA). RESEARCH DESIGN AND METHODS: We retrospectively analyzed the data of 85 people with diagnosed SAA who underwent p-ALG plus CsA, with or without TPO-RA from 2014 to 2023. RESULTS: The overall response rates were 55.3% and 65.9% at 3 and 6 months, and the TPO-RA group were 66.7% and 72.3% at 3 and 6 months, without TPO-RA group were 27.8% and 55.6%. In multivariate analysis, baseline platelet count of > 10 × 109/L was a simple predictor of favorable response at 6 months (p = 0.015). The median follow-up time for all patients was 39 months (range 0.4 ~ 104), the 5-year overall survival (OS) rate was 90.6% [95% CI = 82.1-95.2%], and the failure-free survival (FFS) rate was 68.9% [95% CI = 56.6-78.4%]. Having hematologic responses in 6 months was an independent positive predictor for FFS (p = 0.000). Twelve patients (14.1%) suffered from serum sickness, and 9.5% of patients had mild hepatic impairment. CONCLUSIONS: p-ALG along with CsA is an effective choice for patients with SAA. p-ALG combined with TPO-RA may contribute to the early restoration of hematopoiesis.

Evaluating Leukocyte Telomere Length and Myeloid-Derived Suppressor Cells as Biomarkers for Prostate Cancer.

BACKGROUND: Leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) are associated with aging and the development and progression of cancer. However, the exact nature of this relationship remains unclear. Our study aimed to investigate the potential of LTL and MDSC as diagnostic biomarkers for prostate cancer while also seeking to deepen our understanding of the relationship of these potential biomarkers to each other. METHODS: Our study involved patients undergoing a prostate biopsy. We analyzed the relative LTL in genomic DNA obtained from peripheral blood leukocytes as well as the percentage of MDSC and their subtypes in peripheral blood mononuclear cells (PBMC). Our evaluation focused on examining the relationship between LTL and MDSC and pathological diagnoses as well as investigating the correlation between LTL and MDSC levels. RESULTS: In our study of 102 participants, 56 were pathologically diagnosed with localized prostate cancer (cancer group), while 46 tested negative (control group). The cancer group exhibited significantly shorter LTL in comparison to the control group (p = 0.024). Additionally, the cancer group showed a tendency towards a higher percentage of monocytic MDSC (M-MDSC), although this difference did not reach statistical significance (p = 0.056). Our multivariate logistic regression analysis revealed that patients with shorter LTL and higher percentages of M-MDSC had a 2.98-fold (95% CI = 1.001-8.869, p = 0.049) and 3.03-fold (95% CI = 1.152-7.977, p = 0.025) increased risk of prostate cancer diagnosis, respectively. There was also a significant negative correlation between LTL and M-MDSC. (r = -0.347, p < 0.001). CONCLUSIONS: Our research has established a correlation between LTL and MDSC in patients undergoing biopsy for prostate cancer. Notably, we observed that individuals with localized prostate cancer tend to have shorter LTL and a higher percentage of M-MDSC prior to their diagnosis. These findings suggest that LTL and M-MDSC could potentially serve as adjunctive biomarkers for the early diagnosis of prostate cancer.

The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant cancer worldwide, characterized by high morbidity and mortality rates. Alpha-fetoprotein (AFP) is a glycoprotein synthesized by the liver and yolk sac during fetal development. However, the serum levels of AFP exhibit a significant correlation with the onset and progression of HCC in adults. Extensive research has demonstrated that the tumor microenvironment (TME) plays a crucial role in the malignant transformation of HCC, and AFP is a key factor in the TME, promoting HCC development. The objective of this review was to analyze the existing knowledge regarding the role of AFP in the TME. Specifically, this review focused on the effect of AFP on various cells in the TME, tumor immune evasion, and clinical application of AFP in the diagnosis and treatment of HCC. These findings offer valuable insights into the clinical treatment of HCC.

Spectroscopic Identification of Trifluorosilylphosphinidene and Isomeric Phosphasilene and Silicon Trifluorophosphine Complex.

The perfluorinated silylphosphinidene, F3SiP, in the triplet ground state is generated by the reaction of laser-ablated silicon atoms with PF3 in solid neon and argon matrices. The reactions proceed with the initial formation of a silicon trifluorophosphine complex, F3PSi, in the triplet ground state, and a more stable inserted phosphasilene, FPSiF2, in the singlet ground state upon deposition. The trifluorosilylphosphinidene was formed through F-migration reactions of FPSiF2 and F3PSi following a two-state mechanism under irradiation with visible light (λ = 470 nm) and full arc light (λ > 220 nm), respectively. High-level quantum-chemical methods support the identification of F3PSi, FPSiF2, and F3SiP by matrix-isolation IR spectroscopy.