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Abstract Objective This study aims to evaluate the clinical management and effectiveness of metagenomic next-generation sequencing (mNGS) in patients with pyogenic spinal infections. Methods We conducted a retrospective review of 17 patients diagnosed with pyogenic spinal infections and treated at our institution between October 2022 and February 2024. The cohort included 8 males and 9 females, with a mean age of 63.59 ± 10.18 years (range: 41–71 years). The infections comprised 9 epidural abscesses, 6 intervertebral space infections, and 2 deep abscesses. All patients underwent open surgical procedures and mNGS-based bacterial identification using intraoperative pus or tissue specimens, in addition to conventional blood bacterial cultures. Clinical outcomes were assessed using CRP, PCT, WBC inflammatory markers, and VAS scores postoperatively. Results All 17 patients with pyogenic spinal infections underwent open surgery and mNGS bacterial detection at our institution. Among the 17 patients, mNGS yielded positive results in 14 cases (82.4%), significantly higher than the 5.9% positivity rate of conventional bacterial cultures (p

Abstract Background To discuss the current status of reproductive concerns and its correlation with fear of recurrence and level of family support in patients of childbearing age with gynecologic malignancies. Methods A convenient sampling method was used to enroll 188 patients with gynecologic malignancies in Nanjing Maternity and Child Health Care Hospital, Nanjing Drum Tower Hospital, General Hospital of Ningxia Medical University, and Haian Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from September 2022 to April 2023. Patients were assessed using general information questionnaire, Reproductive Concerns After Cancer Scale (RCAC), Fear of Cancer Recurrence Inventory (FCRI) questionnaire, and Perceived Social Support-Family (PSS-FA) Scale. Results Among patients of childbearing age with gynecologic malignancies, the total RCAC score was (54.35 ± 7.52), indicating a moderate level of reproductive concerns. Patients scored (20.98 ± 4.51) on FCRI, implying a moderate level of fear of recurrence. The PSS-FA score was (9.57 ± 2.76), denoting a moderate level of family support. The total score and each dimensional score of RCAC were positively correlated with FCRI total score (P

The study aimed to determine the in vitro digestive properties of wolfberry multigrain meal replacement powders with a low glycemic index (GI). The basic components, water absorption and swelling rate, starch components, starch hydrolysis rate, and estimated glycemic index (eGI) of each raw material powder and meal replacement powder were measured. The changes in protein hydrolysis rate, total phenolic content, flavonoid content and antioxidant activity in each raw material powder and meal replacement powder were comparatively analyzed by in vitro simulation of gastrointestinal digestive methods. The results showed that the contents of fat and crude fiber in the meal replacement powder were lower than the raw material powders. The water absorption rate of each raw material powder and meal replacement powder at a high temperature was approximately two times of that at room temperature, among which the meal replacement powder had the lowest water absorption rate (0.27%±0.05% at room temperature and 0.59%±0.05% at a high temperature). The rapidly digestion starch content (40.4%±0.003%) and eGI value (23.4) of the meal replacement powder were the lowest among all the ingredient powders, while the slowly digestion starch and resistant starch contents were both relatively high. In the in vitro simulated gastrointestinal digestion experiment, the protein hydrolysis rate of each raw material powder and meal replacement powder gradually increased and the hydrolysis was mainly in the stomach, in which the protein hydrolysis rate of the meal replacement powder was relatively high. The total phenol content tended to increase during gastrointestinal digestion, and the meal replacement powder reached the highest content at the end of digestion (7.26 mg/g). The flavonoid content increased significantly during simulated gastric digestion and decreased in simulated intestinal digestion. DPPH and ABTS+ radical scavenging rates increased significantly (P

Background Hibiscus mutabilis L. is a popular regional characteristic plant in China, cultivated for its attractive flower colors, extended bloom time, and medicinal properties. To enhance molecular breeding and gene function studies, we conducted transcriptome analysis and identified valuable genes in previous research. Nonetheless, the current inefficient and labor-intensive transformation techniques have hindered their applications. Virus-induced gene silencing (VIGS) provides a precise and effective strategy for post-transcriptional down-regulation of endogenous gene expression. Methods We investigated the performance of tobacco rattle virus (TRV) as a tool for targeting and silencing the gene encoding the protein involved in chloroplast development, cloroplastos alterados 1 (altered chloroplast; CLA1), of H. mutabilis through Agrobacterium tumefaciens-mediated infiltration. Results By effectively suppressing the CLA1 gene associated with chloroplast development in H. mutabilis via the TRV-VIGS system, we have illustrated the inaugural implementation of VIGS in this species. Quantitative RT-PCR proved that HmCLA1 expression in agro-infiltrated plants was lower than in the mock-infiltrated (mock) and the control (CK) plants. Phenotypic observations corroborated the albino phenotype in leaves following successful HmCLA1 silencing. Conclusions Our study showcases TRV-VIGS as a potential gene silencing tool for H. mutabilis, facilitating functional genomics studies and molecular breeding efforts in this species.

Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.

Abstract FBXO32, a member of the F-box protein family, is known to play both oncogenic and tumor-suppressive roles in different cancers. However, the functions and the molecular mechanisms regulated by FBXO32 in lung adenocarcinoma (LUAD) remain unclear. Here, we report that FBXO32 is overexpressed in LUAD compared with normal lung tissues, and high expression of FBXO32 correlates with poor prognosis in LUAD patients. Firstly, we observed with a series of functional experiments that FBXO32 alters the cell cycle and promotes the invasion and metastasis of LUAD cells. We further corroborate our findings using in vivo mouse models of metastasis and confirmed that FBXO32 positively regulates LUAD tumor metastasis. Using a proteomic-based approach combined with computational analyses, we found a positive correlation between FBXO32 and the PI3K/AKT/mTOR pathway, and identified PTEN as a FBXO32 interactor. More important, FBXO32 binds PTEN via its C-terminal substrate binding domain and we also validated PTEN as a bona fide FBXO32 substrate. Finally, we demonstrated that FBXO32 promotes EMT and regulates the cell cycle by targeting PTEN for proteasomal-dependent degradation. In summary, our study highlights the role of FBXO32 in promoting the PI3K/AKT/mTOR pathway via PTEN degradation, thereby fostering lung adenocarcinoma progression.

Abstract ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low‐risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low‐risk ETV6::RUNX1‐positive B‐cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome‐wide transcriptome and single‐nucleotide variants. We found high TIMD4 expression (> 85th‐percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low‐risk ETV6::RUNX1‐positive B‐cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low‐risk ETV6::RUNX1‐negative B‐cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low‐risk B‐cell ALL in children might be associated with high risk for early relapse.

The long-trunked elephantids underwent a significant evolutionary stage characterized by an exceptionally elongated mandible. The initial elongation and subsequent regression of the long mandible, along with its co-evolution with the trunk, present an intriguing issue that remains incompletely understood. Through comparative functional and eco-morphological investigations, as well as feeding preference analysis, we reconstructed the feeding behavior of major groups of longirostrine elephantiforms. In the Platybelodon clade, the rapid evolutionary changes observed in the narial region, strongly correlated with mandible and tusk characteristics, suggest a crucial evolutionary transition where feeding function shifted from the mandible to the trunk, allowing proboscideans to expand their niches to more open regions. This functional shift further resulted in elephantids relying solely on their trunks for feeding. Our research provides insights into how unique environmental pressures shape the extreme evolution of organs, particularly in large mammals that developed various peculiar adaptations during the late Cenozoic global cooling trends.

Abstract Background Cancer-derived exosomes contribute significantly in intracellular communication, particularly during tumorigenesis. Here, we aimed to identify two immune-related ovarian cancer-derived exosomes (IOCEs) subgroups in ovarian cancer (OC) and establish a prognostic model for OC patients based on immune-related IOCEs. Methods The Cancer Genome Atlas (TCGA) database was used to obtain RNA-seq data, as well as clinical and prognostic information. Consensus clustering analysis was performed to identify two IOCEs-associated subgroups. Kaplan-Meier analysis was used to compare the overall survival (OS) between IOCEs-high and IOCEs-low subtype. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to investigate the mechanisms and biological effects of differentially expressed genes (DEGs) between the two subtypes. Besides, an IOCE-related prognostic model of OC was constructed by Lasso regression analysis, and the signature was validated using GSE140082 as the validation set. Results In total, we obtained 21 differentially expressed IOCEs in OC, and identified two IOCE-associated subgroups by consensus clustering. IOCE-low subgroup showed a favorable prognosis while IOCE-high subgroup had a higher level of immune cell infiltration and immune response. GSEA showed that pathways in cancer and immune response were mainly enriched in IOCE-high subgroup. Thus, IOCE-high subgroup may benefit more in immunotherapy treatment. In addition, we constructed a risk model based on nine IOCE-associated genes (CLDN4, AKT2, CSPG5, ALDOC, LTA4H, PSMA2, PSMA5, TCIRG1, ANO6). Conclusion We developed a novel stratification system for OV based on IOCE signature, which could be used to estimate the prognosis as well as immunotherapy for OC patient.

This study identified a salt-tolerant GH11 xylanase, Xynst, which was isolated from a soil bacterium Bacillus sp. SC1 and can resist as high as 4 M NaCl. After rational design and high-throughput screening of site-directed mutant libraries, a double mutant W6F/Q7H with a 244% increase in catalytic activity and a 10 °C increment in optimal temperature was obtained. Both Xynst and W6F/Q7H xylanases were stimulated by high concentrations of salts. In particular, the activity of W6F/Q7H was more than eight times that of Xynst in the presence of 2 M NaCl at 65 °C. Kinetic parameters indicated they have the highest affinity for beechwood xylan (Km = 0.30 mg mL−1 for Xynst and 0.18 mg mL−1 for W6F/Q7H), and W6F/Q7H has very high catalytic efficiency (Kcat/Km = 15483.33 mL mg−1 s−1). Molecular dynamic simulation suggested that W6F/Q7H has a more compact overall structure, improved rigidity of the active pocket edge, and a flexible upper-end alpha helix. Hydrolysis of different xylans by W6F/Q7H released more xylooligosaccharides and yielded higher proportions of xylobiose and xylotriose than Xynst did. The conversion efficiencies of Xynst and W6F/Q7H on all tested xylans exceeded 20%, suggesting potential applications in the agricultural and food industries.

PurposeThis study aimed to investigate the characteristics of various pulmonary lesions as revealed by 68Ga-FAPI PET/CT and to determine the utility of 68Ga-FAPI PET/CT in distinguishing the nature of these pulmonary lesions.MethodsA retrospective analysis was conducted on 99 patients with pulmonary lesions, who were categorized into three distinct groups: primary lung tumors (G1), metastatic lung tumors (G2), and benign lesions (G3). Each participant underwent a 68Ga-FAPI PET/CT scan. Among these groups, variables such as the Tumor/Background Ratio (TBR), Maximum Standardized Uptake Value (SUVmax), and the true positive rate of the lesions were compared. Furthermore, the FAPI uptake in nodular-like pulmonary lesions (d

East Asia, being the evolutionary center of Coelodonta, offers a unique opportunity to explore the spatiotemporal paleoecologies of this genus. This study utilized bulk and serial stable carbon and oxygen isotope analyses on the Coelodonta nihowanensis and other ungulates from the Longdan fauna as well as two modern goats in the Linxia Basin, aiming to explore the paleoecology of C. nihowanensis at the periphery of the Tibetan Plateau during the Early Pleistocene. The isotopic results of these mammals indicated that C3 vegetation was possibly a major component of the local environment in the Linxia Basin, which was influenced by a seasonal summer monsoon. C. nihowanensis specimens in the Longdan fauna were possibly mixed feeders, as indicated by the wide distribution of their δ13C values and the intermediate δ18O values compared to other coexisting ungulates. Moreover, the comparison of the δ13C and δ18O values of similar taxa from the Linxia and Nihewan basins has revealed spatiotemporal differences in the paleoclimate and paleoenvironments of these two regions throughout the Early Pleistocene. This provides a holistic framework for understanding the paleoecology of the C. nihowanensis. The isotopic results of the C. nihowanensis in the Linxia and Nihewan basins suggested varied foraging ecologies across different sites and time spans during the Early Pleistocene. This underscores the adaptability of the C. nihowanensis to diverse environments from west to east in northern China. By scrutinizing the evolutionary ecological history of the woolly rhinoceroses from its ancestor, Coelodonta thibetana, to its final form, Coelodonta antiquitatis, this study sheds light on the ecological adaptation of this genus from the Pliocene to Late Pleistocene, spanning its migration from the Tibetan Plateau to northern Eurasia.

Abstract Objective We aimed to perform a qualitative synthesis of evidence on the role of 68Ga-Pentixafor PET in atherosclerosis. Methods A systematic search of the PubMed and Embase databases for studies reporting the evaluation of atherosclerotic lesions by 68Ga-Pentixafor PET was performed with a search time frame from database creation to 2022-12-26. The diagnostic test evaluation tool QUADAS-2 was used to evaluate the quality of the included literature and to perform descriptive analyses of relevant outcome indicators. Results A total of 6 studies with 280 patients were included. One study reported only imaging outcome metrics, while the other five studies reported imaging outcome metrics and clinical correlation metrics. For imaging outcomes, three studies reported imaging results for 68Ga-Pentixafor PET only, and the other three studies reported imaging results for comparative analysis of 68Ga-Pentixafor PET with 18F-FDG PET. For clinical correlation, three studies reported the correlation between tracer uptake and cardiovascular risk factors, one study reported the correlation between tracer uptake and plaque calcification, and one study reported the correlation between all three: tracer uptake, cardiovascular risk factors, and plaque calcification. Conclusion 68Ga-Pentixafor PET has a good imaging effect on atherosclerotic lesions, and it is a promising imaging modality that may replace 18F-FDG PET for atherosclerosis imaging in the future. In patients with atherosclerosis, there is a clear clinical correlation between cardiovascular risk factors, tracer uptake, and plaque calcification.

Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is a global economic pest that poses a serious threat to the fruit industry. In the southwest of China, Yunnan Province sustains a severe infestation of B. dorsalis. An automated monitoring system designed for B. dorsalis was employed in this study to elucidate the annual population dynamics of B. dorsalis in four counties: Yuanjiang, Huaping, Guangnan, and Ludian in Yunnan. The system utilizes sex parapheromone and image recognition technology. The data uploaded by the device are used to analyze the annual population dynamics of B. dorsalis in different regions. The results showed that the populations of adult B. dorsalis in all four counties peaked twice annually, with Yuanjiang experiencing the earliest peak periods, followed by Huaping, Guangnan, and Ludian. Adult B. dorsalis occurred in Yuanjiang throughout the year, and Yuanjiang had the highest number of B. dorsalis monitored. In Huaping, adult B. dorsalis occurred in March–December and was highly active, with a high population density in 2019. Bactrocera dorsalis did not occur in December in Guangnan but only in May–October in Ludian. Bactrocera dorsalis abundance was correlated with temperature in all four areas. The outcomes of this experiment provide a practical foundation for developing control strategies targeting B. dorsalis in various orchards across each county.

The synthesis of alternative fuels from biomass has emerged to be a vital strategy to maintain sustainable development. Long-chain levulinate esters (LEs) are a class of good biofuel candidates because they have similar structures to biodiesels and superior heating values. The synthesis of long-chain LEs with effective heterogeneous catalysts has always been challenging. In this work, a few heterogeneous phosphotungstate catalysts were facilely prepared, among which the V3+ exchanged phosphotungstic acid catalyst (VPW) was the most active for the alcoholysis of furfuryl alcohol (FA) and 1-hexanol into 1-hexyl levulinate (HL). A maximum HL yield of 63% was achieved at 180 °C. The VPW catalyst could be reused without obvious decrement of activity. The system was also applicable to the alcoholysis of FA with other hexanols and 1-octanol into various long-chain LEs.

Abstract Temporal lobe epilepsy (TLE), one common type of medically refractory epilepsy, is accompanied with altered adult-born dentate granule cells (abDGCs). However, the causal role of abDGCs in recurrent seizures of TLE is not fully understood. Here, taking advantage of optogenetic and chemogenetic tools to selectively manipulate abDGCs in a reversible manner, combined with Ca2+ fiber photometry, trans-synaptic viral tracing, in vivo/vitro electrophysiology approaches, we aimed to test the role of abDGCs born at different period of epileptogenic insult in later recurrent seizures in mouse TLE models. We found that abDGCs were functionally inhibited during recurrent seizures. Optogenetic activation of abDGCs significantly extended, while inhibition curtailed, the seizure duration. This seizure-modulating effect was attributed to specific abDGCs born at a critical early phase after kindled status, which experienced specific type of circuit re-organization. Further, abDGCs extended seizure duration via local excitatory circuit with early-born granule cells (ebDGCs). Repeated modulation of “abDGC-ebDGC” circuit may easily induce a change of synaptic plasticity, and achieve long-term anti-seizure effects in both kindling and kainic acid-induced TLE models. Together, we demonstrate that abDGCs born at a critical period of epileptogenic insult maintain seizure duration via local aberrant excitatory circuits, and inactivation of these aberrant circuits can long-termly alleviate severity of seizures. This provides a deeper and more comprehensive understanding of the potential pathological changes of abDGCs circuit and may be helpful for the precise treatment in TLE.

BackgroundThe inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has made significant contributions to fighting the epidemic in the past three years. However, the rapid development and application raised concerns about its safety in reproductive health, especially after several studies had observed a decrease in semen parameters following two doses of mRNA SARS-CoV-2 vaccination. Thus, it is necessary to comprehensively evaluate the effect of inactivated SARS-CoV-2 vaccine on male fertility.MethodsA retrospective cohort study was conducted in the Center for Reproductive Medicine of the Affiliated Hospital of Jining Medical University between July 2021 and March 2023. A total of 409 men with different vaccination status and no history of SARS-CoV-2 infection were included in this study. Their sex hormone levels and semen parameters were evaluated and compared separately.ResultsThe levels of FSH and PRL in one-dose vaccinated group were higher than other groups, while there were no significant changes in other sex hormone levels between the control and inactivated SARS-CoV-2 vaccinated groups. Most semen parameters such as volume, sperm concentration, total sperm count, progressive motility and normal forms were similar before and after vaccination with any single dose or combination of doses (all P > 0.05). Nevertheless, the total motility was significantly decreased after receiving the 1 + 2 doses of vaccine compared to before vaccination (46.90 ± 2.40% vs. 58.62 ± 2.51%; P = 0.001). Fortunately, this parameter was still within the normal range.ConclusionOur study demonstrated that any single dose or different combined doses of inactivated SARS-CoV-2 vaccination was not detrimental to male fertility. This information could reassure men who want to conceive after vaccination and be incorporated into future fertility recommendations.

BackgroundAphasia is one of the most common complications of stroke. Mirror therapy (MT) is promising rehabilitation measure for the treatment of post-stroke aphasia. Although some studies suggested that MT is effective and safe for aphasia, the effects and safety remain uncertain due to lacking strong evidence, such as the relevant systematic review and meta- analysis.MethodsThis study will search PubMed, Web of Science, Cochrane Library, EMBASE, Medline, China Knowledge Network (CNKI), WANFANG, China Biomedical Literature Database (CBM), from inception to 1th May 2023 to identify any eligible study. No language or date of publication shall be limited. We will only include randomised controlled trials of MT in the Treatment of poststroke aphasia. Two investigators will work separately on the study selection, data extraction, and study quality assessment. The western aphasia battery (WAB) and aphasia quotient (AQ) will be included as the main outcomes. Boston diagnostic aphasia examination method (BDAE), Chinese standard aphasia examination (CRRCAE) will be included as the secondary outcomes. The statistical analysis will be conducted by RevMan V.5.4 software. The risk of bias of included studies will be assessed by the Cochrane 'Risk of bias' tool. The quality of proof of the results will be evaluated by using the Grading of Recommendations Assessment, Development and Evaluation guidelines.ResultsThe finding will be presented in a journal or related conferences.ConclusionThis study will provide a basis for whether mirror therapy (MT) is effective and safe in the treatment of post-stroke aphasia.Trial registrationSystematic review registration INPLASY registration number: INPLASY 202340054.

The coronavirus disease 2019 (COVID-19) pandemic has posed a serious threat to global healthcare and economy. In order to curb its spread, China adopted the dynamic zero-COVID policy, aiming to diagnose and isolate cases and close contacts as soon as possible. However, there is a controversy about the impact of isolation measures on social order, including the economy, personal employment and public mental health. Therefore, this review discusses and analyzes in detail the advantages and challenges of implementing dynamic zero-COVID policy. Although this public health policy might cause a shock to the economy in the short term, China still achieved a continued healthy economic performance with stable unemployment and strong export growth. Moreover, the rates of infection and mortality in China were lower than those in the United States and the European Union. However, due to the high transmissibility and low pathogenicity of the Omicron variant and prolonged lockdown-induced psychological damage, people questioned the effectiveness and necessity of this policy. Now that China has adjusted its policy in a timely manner, but many problems still remain unsolved. Some practical suggestions in terms of mental health, vaccine development, drugs supply, and economic recovery are put forward at the end of our paper to minimize negative impacts and provide a reference for future efforts.

Underground coal gasification (UCG) is consistent with the development of low-carbon green transformation of energy in China. However, the groundwater pollution caused by it is the bottleneck preventing from the promotion and application of UCG. Permeable reaction barrier (PRB) is one of the research hotspots for in-situ groundwater remediation. In this paper, combined with the characteristics of UCG with shaft, the influence of PRB’s thickness and purification materials on the migration and dispersion of organic pollutants in groundwater, and purification and remediation were investigated by numerical simulation. On the foundation of the advection-diffusion equation (ADE), two hypotheses were introduced: ① The mass transfer involved in the adsorption and purification of pollutants in groundwater is related to: (i) the difference potential between the concentration of pollutants adsorbed in the liquid and solid phases, (ii) the difference potential between the current adsorption concentration of solid phase and the potential maximum adsorption concentration, and (iii) the process time; ② The strong adsorption ability of activated carbon may lead to the gradual accumulation of adsorption concentration in the solid phase and no longer easy desorption with the change of the external liquid phase concentration. Both the migration of pollutants and the adsorption and purification processes were simulated numerically and validated experimentally after that the finite element method and \begin{document}$\theta $\end{document}-format iteration were adapted and the corresponding program were coded in MATLAB. The results show that the remediation is enhanced with the increase of the thickness of PRB, but at a declining acceleration, and the marginal effect of the wall thickness increase on the purification shows the diminishing trend. The stronger the adsorption and purification rate of the wall material is, the better the purification of the PRB on pollutants will be, and the adsorption and purification rate also shows a diminishing trend of marginal effect on the purification. There is a synergistic influence between the thickness and the adsorption activity of the material, thus the thickness of PRB should be determined reasonably according to the adsorption and purification rate of the material when constructing PRB in order to obtain the best technical and economic consequence.

PurposeTo verify the International Chronic Ocular Graft-Versus-Host Disease (ICCGVHD) Group diagnostic criteria and establish an easy-to-use and reliable diagnosis model for quick identification of chronic oGVHD.MethodsThis study included 180 patients (355 eyes) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and visited the Peking University Third Hospital Cornea and Ocular Surface Disease Specialist Clinic from July 2020 to February 2021. The proportion of chronic oGVHD was 76.06% (279/355).ResultsFive complaints, including eye dryness, photophobia, foreign body sensation, eye redness, and burning sensation; six ophthalmic examinations, including Ocular Surface Disease Index (OSDI) score, corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer’s test score without anesthesia, conjunctival score, tear meniscus height, and non-ocular GVHD-involved organs were significantly different between patients with chronic oGVHD and control group (p

The accurate characterization and prediction of current–voltage (I–V) characteristics of photovoltaic (PV) modules under different weather conditions are essential for solar power forecasting and ensuring grid stability. This paper proposed a novel method based on the power-law model (PLM) for estimating PV module performance under different weather conditions without setting reference conditions. The effects of solar irradiance, ambient temperature, and module types are all fully considered. The dependence of shape parameters in PLM on irradiance and temperature are thoroughly investigated and the effect of the selection of reference conditions is eliminated by modifying a set of new transforming equations. The parameters of the new transforming equations can be extracted from experimental data by an optimization algorithm. Due to the advantages of PLM, the proposed method applies to any type of PV module and the I–V characteristics can be expressed explicitly without Lambert W-function or iterative solution. The effectiveness and accuracy proposed method are verified and tested on the large datasets of eighteen PV modules in three locations. Compared with existing methods, the proposed method shows higher accuracy and better performance in the estimation of I–V characteristics and maximum power under different weather conditions.

BackgroundWhile recent studies have separately explored mutational signatures and the tumor microenvironment (TME), there is limited research on the associations of both factors in a pan-cancer context.Materials and methodsWe performed a pan-cancer analysis of over 8,000 tumor samples from The Cancer Genome Atlas (TCGA) project. Machine learning methods were employed to systematically explore the relationship between mutational signatures and TME and develop a risk score based on TME-associated mutational signatures to predict patient survival outcomes. We also constructed an interaction model to explore how mutational signatures and TME interact and influence cancer prognosis.ResultsOur analysis revealed a varied association between mutational signatures and TME, with the Clock-like signature showing the most widespread influence. Risk scores based on mutational signatures mainly induced by Clock-like and AID/APOBEC activity exhibited strong pan-cancer survival stratification ability. We also propose a novel approach to predict transcriptome decomposed infiltration levels using genome-derived mutational signatures as an alternative approach for exploring TME cell types when transcriptome data are unavailable. Our comprehensive analysis revealed that certain mutational signatures and their interaction with immune cells significantly impact clinical outcomes in particular cancer types. For instance, T cell infiltration levels only served as a prognostic biomarker in melanoma patients with high ultraviolet radiation exposure, breast cancer patients with high homologous recombination deficiency signature, and lung adenocarcinoma patients with high tobacco-associated mutational signature.ConclusionOur study comprehensively explains the complex interplay between mutational signatures and immune infiltration in cancer. The results highlight the importance of considering both mutational signatures and immune phenotypes in cancer research and their significant implications for developing personalized cancer treatments and more effective immunotherapy.

Abstract Purpose To determine the role tear lymphotoxin-α (LT-α) in chronic ocular graft-versus-host disease (oGVHD). Methods Twenty-two chronic oGVHD and 17 control tear samples were collected, and commercial test strips were used to detect LT-α concentrations. Concentration differences between patients with and without oGVHD were determined via Mann-Whitney U test. The correlation between LT-α levels and ophthalmic parameters was analyzed using Spearman’s test. Results The concentration of LT-α was significantly lower in oGVHD patients than in controls. LT-α levels were significantly correlated with OSDI, NIH eye score, T-BUT, and CFS among all participants. ROC analysis revealed that the area under the curve of LT-α was 0.847, and the cutoff value for chronic oGVHD diagnosis was 0.203 ng/mL. Conclusion Our study revealed the significant decrease of tear LT-α in oGVHD, and suggested LT-α as a promising marker for chronic oGVHD diagnosis.

ObjectiveTo perform a meta-analysis of the efficacy and safety about 177Lu-DOTATATE therapy for advanced/metastatic pNETs based on the current clinical evidence.MethodsThis systematic review follows the PRISMA guideline. Search PubMed, Medline, EMBASE and CNKI, VIP, Wanfang databases, from establishment to June 2022, on the study of 177Lu-DOTATATE for advanced/metastatic pNETs, the primary endpoint was to evaluate the treatment effect through DRRs and DCRs. Secondary endpoint included assessment of OS, PFS, and treatment-related adverse events across all studies. Two researchers conducted literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria. Meta-analysis was performed using stata16.0 software, and the data were merged and displayed using forest graphs.ResultsA total of 5 studies, 174 patients, on 177Lu-DOTATATE for advanced/metastatic pNETs were included. The pools of DRRs and DCRs were 24% (95% CI: 15%~32%) and 77% (95% CI: 62%~92%), respectively. The pool of OS was 48.78 months (95% CI: 41~56.57 months) and the pool of PFS was 21.59 months (95% CI: 17.65~25.53 months). In all studies, the most common side effect of treatment was hematological toxicity. In 174 patients, hematological toxicity of grade III accounted for 4.0% (7/174), and only 4.0% (7/174) and 1.0% (2/174) of patients had mild nephrotoxicity and hepatotoxicity. Gastrointestinal adverse reactions in 3% (6/174), nausea in 2% (3/174), superior vena cava occlusion in 0.5% (1/174).Conclusion177Lu-DOTATATE is effective and safe for advanced/metastatic pNETs, which can delay the progression of the disease, may improve patients’ survival, and has low treatment-related toxicity and high safety. However, its efficacy and safety need to be further evaluated in high-quality, multicenter randomized controlled trials in the future.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022344436.

ObjectiveThis study aims to perform a systemic analysis of [68Ga]Ga-DOTA-FAPI-04 positron emission tomography (PET)/computerized tomography (CT) and [18F]FDG PET/CT for the diagnosis of malignant tumor bone metastasis based on existing clinical evidence.MethodsThis systematic review followed the guidelines of the Preferred Reporting Project (PRISMA) for systematic reviews and meta-analysis. This is a retrospective study of articles published in PubMed. Embase was searched online from the start of May 2022. The main endpoints were the maximum standardized uptake value and the tumor-to-background ratio to determine the examination performance of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG for bone transfer stoves. Based on the entry and discharge standards, two researchers extracted documents and data and then performed the quality evaluation.ResultsA total of eight studies on the metastasis of malignant tumors on bone were included, which involved 358 patients in the final analysis.Conclusion[68Ga]Ga-DOTA-FAPI-04 showed better detection performance for bone metastasis. The sensitivity of [68Ga]Ga-DOTA-FAPI-04 for the diagnosis of the primary tumor was higher than that of [18F]FDG, whereas the specificity of [18F]FDG was higher than that of [68Ga]Ga-DOTA-FAPI-04. However, further randomized controlled trials and prospective clinical trials are warranted to compare the diagnostic performance of [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]FDG PET/CT.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022313019)

In this study, we used combined transcriptomics and metabolomics to analyze the H. mutabilis cultivar’s genetic and physiological mechanisms during three flower color transition periods (from white to pink, then from pink to red) within the span of one day. As a result, 186 genes were found to be significantly increased with the deepening of the H. mutabilis flower color; these genes were mainly involved in the expression of peroxidase 30, zinc finger protein, phosphate transporter PHO1, etc. In contrast, 298 genes were significantly downregulated with the deepening of H. mutabilis flower color, including those involved in the expression of probable O-methyltransferase 3, copper binding protein 9, and heat stress transcription factor A-6b. Some genes showed differential expression strategies as the flower color gradually darkened. We further detected 19 metabolites that gradually increased with the deepening of the H. mutabilis flower color, including L-isoleucine, palmitic acid, L-methionine, and (+)-7-isonitrobenzene. The content of the metabolite hexadecanedioate decreased with the deepening of the H. mutabilis flower color. Combined transcriptomics and metabolomics revealed that the metabolic pathways, including those related to anthocyanin biosynthesis, cysteine and methionine metabolism, and sulfur metabolism, appear to be closely related to H. mutabilis flower color transition. This study served as the first report on the genetic and physiological mechanisms of short-term H. mutabilis flower color transition and will promote the molecular breeding of ornamental cultivars of H. mutabilis.

Wheat straw, a typical agricultural solid waste, was employed to clarify the effects of torrefaction on the structural features and combustion reactivity of biomass. Two typical torrefaction temperatures (543 K and 573 K), four atmospheres (argon, 6 vol.% O2, dry flue gas and raw flue gas) were selected. The elemental distribution, compositional variation, surface physicochemical structure and combustion reactivity of each sample were identified using elemental analysis, XPS, N2 adsorption, TGA and FOW methods. Oxidative torrefaction tended to optimize the fuel quality of biomass effectively, and the enhancement of torrefaction severity improved the fuel quality of wheat straw. The O2, CO2 and H2O in flue gas could synergistically enhance the desorption of hydrophilic structures during oxidative torrefaction process, especially at high temperatures. Meanwhile, the variations in microstructure of wheat straw promoted the conversion of N-A into edge nitrogen structures (N-5 and N-6), especially N-5, which is a precursor of HCN. Additionally, mild surface oxidation tended to promote the generation of some new oxygen-containing functionalities with high reactivity on the surface of wheat straw particles after undergoing oxidative torrefaction pretreatment. Due to the removal of hemicellulose and cellulose from wheat straw particles and the generation of new functional groups on the particle surfaces, the ignition temperature of each torrefied sample expressed an increasing tendency, while the Ea clearly decreased. According to the results obtained from this research, it could be concluded that torrefaction conducted in a raw flue gas atmosphere at 573 K would improve the fuel quality and reactivity of wheat straw most significantly.

Memory T cells are particularly reliant on fatty acid oxidation as a source of energy. Here the authors show this reliance is controlled by AMPK sensing of glucose deprivation that triggers SENP1-Sirt3 signalling, driving fatty acid oxidation and memory differentiation in T cells via deacetylation of YME1L1 to induce mitochondrial fusion.

With the increasing demand for fuel causing serious environmental pollution, it is urgent to develop new and environmentally friendly energy conversion devices. These energy conversion devices, however, require good, inexpensive materials for electrodes and so on. The multifunctional properties of porphyrins enable framework materials (e.g., metal-organic frameworks and covalent organic frameworks) to be applied in energy conversion devices due to their simple synthesis, high chemical stability, abundant metallic active sites, adjustable crystalline structure and high specific surface area. Herein, the types of porphyrin structural blocks are briefly reviewed. They can be used as organic ligands or directly assembled with framework materials to generate high-performance electro-/photo-catalysts. These types of catalysts applied in electro-/photo-catalytic water splitting, electro-/photo-catalytic carbon dioxide reduction, and electrocatalytic oxygen reduction are also summarized and introduced. At the end of the article, we present the challenges of porphyrin-based framework materials in the above application and corresponding solutions. We expect porphyrin-based framework materials to flourish energy conversion in the coming years.

Abstract Background Premature ovarian insufficiency (POI) is an ovarian dysfunction that seriously affects a woman’s physiological health and reproduction. Mesenchymal stem cell (MSC) transplantation offers a promising treatment option for ovarian restoration in rodent POI models. However, the efficacy and mechanism of it remain unclear. Methods POI mice model was generated by cyclophosphamide and busulfan, followed with the treatment of tail-vein injection of the human umbilical cord mesenchymal stem cells (hUCMSCs). Maternal physiological changes and offspring behavior were detected. To reveal the pathogenesis and therapeutic mechanisms of POI, we first compared the metabolite profiles of healthy and POI ovarian tissues using untargeted metabolomics analyses. After stem cell therapy, we then collected the ovaries from control, POI, and hUCMSC-treated POI groups for lipid metabolomics and pseudotargeted metabolomics analysis. Results Our results revealed remarkable changes of multiple metabolites, especially lipids, in ovarian tissues after POI generation. Following the transplantation of clinical-grade hUCMSCs, POI mice exhibited significant improvements in body weight, sex hormone levels, estrous cycles, and reproductive capacity. Lipid metabolomics and pseudotargeted metabolomics analyses for the ovaries showed that the metabolite levels in the POI group, mainly lipids, glycerophospholipids, steroids, and amino acids changed significantly compared with the controls’, and most of them returned to near-healthy levels after receiving hUCMSC treatment. Meanwhile, we also observed an increase of monosaccharide levels in the ovaries from POI mice and a decrease after stem cell treatment. Conclusions hUCMSCs restore ovarian function through activating the PI3K pathway by promoting the level of free amino acids, consequently improving lipid metabolism and reducing the concentration of monosaccharides. These findings provide potential targets for the clinical diagnosis and treatment of POI.

Abstract In this paper, we obtain the existence and boundedness of Marcinkiewicz integrals with homogeneous kernels on central Campanato spaces. Moreover, the existence and boundedness of multilinear Marcinkiewicz integrals on central Campanato spaces are also deduced. We extend various previous results to central Campanato spaces which can be seen as the local version of Campanato spaces.

ObjectiveTo conduct a meta-analysis of the efficacy and safety of 225Ac-PSMA-617 in the treatment of metastatic castration-resistant prostate cancer based on existing clinical evidence.MethodsSearch for retrospective studies about 225Ac-PSMA-617 in the treatment of metastatic castration-resistant prostate cancer from establishment to July 2021 in PubMed and EMBASE. The primary endpoint was 225Ac-PSMA-617 biochemical response evaluation criteria after treatment [any prostate specific antigen (PSA) decrease and PSA decrease >50% from baseline] to evaluate the treatment effect. Secondary endpoints included assessment of overall survival (OS), progression-free survival (PFS), molecular response, and toxicity for all studies. Two researchers conducted literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria. Use stata16.0 software for analysis, fixed-effects model for data merging and forest plots for display.ResultsA total of 6 retrospective studies, namely, 201 patients, were included in the final analysis. The pooled proportions of patients with decreased PSA and PSA decreased by more than 50% were 87.0% (95% confidence interval, 0.820 to 0.920) and 66.1% (95% confidence interval, 0.596 to 0.726), respectively. The pooled proportions of OS and PFS were 12.5 months (95%CI: 6.2–18.8 months) and 9.1 months (95%CI: 2.6–15.7 months). The patients showing molecular responses were 54% (95% confidence interval: 25–84%). In all studies, the most common side effect of 225Ac-PSMA-617 TAT was xerostomia, with any degree of xerostomia occurring in 77.1% (155 out of 201), and grade III only accounted for 3.0%. The second was 30.3% (61 out of 201) anemia of any degree, and grade III accounts for 7.5% (15 out of 201). Grade III leukopenia and thrombocytopenia were 4.5% (9 out of 201) and 5.5% (11 out of 201), respectively. Only 6 (3.0%) of 201 patients had Grade III nephrotoxicity.Conclusion225Ac-PSMA-617 is an effective and safe treatment option for mCRPC patients, and the toxicity caused by it is relatively low. However, future randomized controlled trials and prospective trials are required in the future to judge the therapeutic effects and survival benefits compared with existing clinical treatments.Systematic Review RegistrationPROSPERO: CRD42021281967.

Hibiscus mutabilis (cotton rose) is a deciduous shrub or small tree of the Malvaceae family. Here, we report a chromosome-scale assembly of the H. mutabilis genome based on a combination of single-molecule sequencing and Hi-C technology. We obtained an optimized assembly of 2.68 Gb with a scaffold N50 length of 54.7 Mb. An integrated strategy of homology-based, de novo, and transcriptome-based gene predictions identified 118,222 protein-coding genes. Repetitive DNA sequences made up 58.55% of the genome, and LTR retrotransposons were the most common repetitive sequence type, accounting for 53.15% of the genome. Through the use of Hi-C data, we constructed a chromosome-scale assembly in which Nanopore scaffolds were assembled into 46 pseudomolecule sequences. We identified important genes involved in anthocyanin biosynthesis and documented copy number variation in floral regulators. Phylogenetic analysis indicated that H. mutabilis was closely related to H. syriacus, from which it diverged approximately 15.3 million years ago. The availability of cotton rose genome data increases our understanding of the species’ genetic evolution and will support further biological research and breeding in cotton rose, as well as other Malvaceae species.

Background: Diffuse large B-cell lymphoma (DLBCL), the most common type of Non-Hodgkin’s Lymphoma (NHL), has a lethal nature. Thus, the establishment of a novel model to predict the prognosis of DLBCL and guide its therapy is an urgency. Meanwhile, pyroptosis is engaged in the progression of DLBCL with further investigations required to reveal the underlying mechanism. Methods: LASSO regression was conducted to establish a risk model based on those PRGs. External datasets, RT-qPCR and IHC images from The Human Protein Alta (HPA) database were utilized to validate the model. ssGSEA was utilized to estimate the score of immune components in DLBCL. Results: A model based on 8 PRGs was established to generate a risk score. Validation of the model confirmed its robust performance. The risk score was associated with advanced clinical stages and shorter overall survivals. Two novel second-line chemotherapies were found to be potential treatments for high-risk patients. The risk score was also found to be correlated with immune components in DLBCL. Conclusion: This novel model can be utilized in clinical practices to predict the prognosis of DLBCL and guide the treatment of patients at high risk, providing an overview of immune regulatory program via pyroptosis in DLBCL.

Fluctuation ('noise') in gene expression is critical for mammalian cellular processes. Numerous mechanisms contribute to its origins, yet the mechanisms behind large fluctuations that are induced by single transcriptional activators remain elusive. Here, we probed putative mechanisms by studying the dynamic regulation of transcriptional activator binding, histone regulator inhibitors, chromatin accessibility, and levels of mRNAs and proteins in single cells. Using a light-induced expression system, we showed that the transcriptional activator could form an interplay with dual functional co-activator/histone acetyltransferases CBP/p300. This interplay resulted in substantial heterogeneity in H3K27ac, chromatin accessibility, and transcription. Simultaneous attenuation of CBP/p300 and HDAC4/5 reduced heterogeneity in the expression of endogenous genes, suggesting that this mechanism is universal. We further found that the noise was reduced by pulse-wide modulation of transcriptional activator binding possibly as a result of alternating the epigenetic states. Our findings suggest a mechanism for the modulation of noise in synthetic and endogenous gene expression systems.

Abstract Background Mesenchymal stem cells (MSCs) have emerged as a promising regenerative tool, owing mainly to their multi-differentiation potential and immunosuppressive capacity. When compared with MSCs classically derived from the adult bone marrow (BM), MSCs of neonatal origins exhibit superior proliferation ability, lower immunogenicity, and possible lower incorporated mutation; hence, they are considered as an alternative source for clinical use. Several researches have focused on the biological differences among some neonatal MSCs cultured in serum-containing medium (SCM). However, since it has been reported that MSCs possess different biological characteristics when cultured in serum-free medium (SFM), these comparative studies in SCM cannot exactly represent the results under the serum-free Good Manufacturing Practice (GMP) standard. Methods Here, MSCs were isolated from three neonatal tissues, namely amniotic membrane (AM), umbilical cord (UC), and chorionic plate (CP), from the same donor, and their morphologies, immunophenotypes, trilineage differentiation potentials, global gene expression patterns, and proliferation abilities were systematically compared under chemical-defined SFM. Results Our study demonstrated that these three neonatal MSCs exhibited a similar morphology and immunophenotypic pattern but various mesodermal differentiation potentials under SFM: amniotic membrane-derived MSCs showed a higher rate for osteogenic differentiation; chorionic plate-derived MSCs presented better adipogenic induction efficiency; and all these three neonatal MSCs exhibited similar chondrogenic potential. Moreover, by the analysis of global gene expression patterns, we speculated a possible higher proliferation ability of CP-MSCs in SFM, and we subsequently validated this conjecture. Conclusions Collectively, these results suggest that MSCs of different neonatal origins possess different biological features in SFM and thus may represent an optimal choice for different clinical applications.

Objectives: This study assessed the associations between long-term trajectories of percentage of energy from fat (PEF) and obesity among Chinese adults. Methods: Longitudinal data collected by the China Health and Nutrition Survey from 1991 to 2015 were analyzed. A body mass index ≥28.0 was defined as general obesity. Participants’ baseline PEF levels were categorized as lower than the recommendation of the Chinese Dietary Guideline (30%). Patterns of PEF trajectories were identified by latent class trajectory analysis for overall participants and participants in different baseline PEF groups, respectively. Cox proportional hazards regression models with shared frailty were used to estimate associations between PEF and obesity. Results: Data on 13,025 participants with 72,191 visits were analyzed. Four patterns of PEF trajectory were identified for overall participants and participants in three different baseline PEF groups, respectively. Among overall participants, compared with “Baseline Low then Increase Pattern” (from 12% to 20%), participants with “Baseline Normal-Low then Increase-to-High Pattern” (from 20% to 32%) had a higher hazard of obesity (hazard ratio (HR) and 95% confident interval (CI) at 1.18 (1.01–1.37)). Compared with the “Stable Pattern” group (stable at around 18% and 22%, respectively), participants with “Sudden-Increase Pattern” (from 18% to 30%) in the baseline group whose PEF levels were lower than the recommendation and those with “Sudden-Increase then Decrease Pattern” (rapidly increased from 25% to 40%, and then decreased) in the baseline group who met the recommendation had higher hazards of obesity (HRs and 95% CIs being 1.65 (1.13–2.41) and 1.59 (1.03–2.46), respectively). Conclusions: Adults with a trajectory that involved a sudden increase to a high-level PEF had a higher risk of general obesity. People should avoid increasing PEF suddenly.

Sirtuin 3 (SIRT3) deacetylase is a key regulator for chemoresistance in acute myeloid leukemia (AML) cells due to its capability of modulating mitochondrial metabolism and reactive oxygen species (ROS). SIRT3 is de-SUMOylated by SUMO-specific peptidase 1 (SENP1), which enhances its deacetylase activity. Therefore, dysregulation of SIRT3 SUMOylation may lead to fortified chemoresistance in AML. Indeed, SIRT3 de-SUMOylation was induced by chemotherapeutic agents, which in turn, exacerbated resistance against chemotherapies in AML by activating SIRT3 via preventing its proteasome degradation. Furthermore, RNA-seq revealed that expression of a collection of genes was altered by SIRT3 de-SUMOylation including inhibition of transcription factor Hes Family BHLH Transcription Factor 1 (HES1), a downstream substrate of Notch1 signaling pathway, leading to increased fatty acids oxidation (FAO). Moreover, the SENP1 inhibitor momordin-Ic or HES1 overexpression synergized with cytarabine to eradicate AML cells in vitro and in xenograft mouse models. In summary, the current study revealed a novel role of SIRT3 SUMOylation in the regulation of chemoresistance in AML via HES1-dependent FAO and provided a rationale for SIRT3 SUMOylation and FAO targeted interventions to improve chemotherapies in AML.

Brain microvascular endothelial cells (BMECs) are a major component of the blood-brain barrier that maintains brain homeostasis. Preserving and restoring the normal biological functions of BMECs can reverse or reduce brain injury. Endothelial progenitor cells (EPCs) may promote brain vascular remodeling and restore normal endothelial function. As a novel vehicle for cell-cell communication, microvesicles (MVs) have varied biological functions. The present study investigated the biological effects of EPC-derived MVs (EPC-MVs) on BMECs in vitro. We isolated MVs from the supernatant of EPCs in a serum-depleted medium. BMECs were cultured alone or in the presence of EPC-MVs. BMEC viability and proliferation were evaluated with the Cell Counting Kit-8 and by flow cytometry, and the proangiogenic effect of EPC-MVs on BMECs was assessed with the transwell migration, wound healing, and tube formation assays. Our results showed that EPC-derived MVs labeled with DiI were internalized by cultured BMECs; this enhanced BMEC viability and promoted their proliferation. EPC-MVs also stimulated migration and tube formation in BMECs. These results demonstrate that EPC-derived MVs exert a proangiogenic effect on BMECs, which has potential applications in cell-free therapy for brain injury.

Fragmentation is a well-characterized degradation pathway of therapeutic antibodies and is usually monitored by capillary electrophoresis–sodium dodecyl sulfate (CE-SDS). Although fragments due to cleavage in CH2 domains linked by intrachain disulfide bonds are common and can be detected by reduced reversed-phase – liquid chromatography mass spectrometry (RP-LCMS) and reduced CE-SDS methods, their separation in nonreduced CE-SDS (nrCE-SDS) has not been reported but speculated as comigrating with intact IgG. A shoulder peak in nrCE-SDS was observed in the stability samples of an IgG-like bispecific antibody and was determined to be mainly caused by fragments from clipping at the C-terminus of leucine (L)306 or L309 (EU numbering) in the CH2 domain of both heavy chains (HCs) and, to a lesser degree, at the C-terminus of L182 in the CH1 domain of the knob HC. Subunit LCMS analysis verified that the crystallizable fragment contained variants with one or multiple mass additions of ~18 Da due to clipping. Further investigation revealed that CH2 clippings at L306 and L309 were largely due to proteolytic activity, and cleavages were present at various levels in all in-house IgG1 and IgG4 molecules studied. Our study shows that CH2 domain cleavages, with complementary fragments still linked by intrachain disulfide, can be electrophoretically resolved as a front shoulder of the main peak in nrCE-SDS. Given the high occurrence of CH2 cleavages in antibodies, these findings will have broad applicability and could help manufacturers of therapeutic antibodies in process improvement, product characterization, investigations, formulation stability, and stability comparability studies.

Bone metastasis of breast cancer causes severe skeletal-related events and poor prognosis. Wensheng Zhuanggu Formula (WSZG), a traditional Chinese prescription, is used to adjunctively treat breast cancer bone metastases in clinical practice. This study was undertaken to investigate the antibone-metastatic activities and mechanisms of WSZG extract by evaluating the effect of this formula on the cross-talk between bone marrow-derived mesenchymal stem cells (BMSCs) and breast cancer cells in triggering epithelial-mesenchymal transition (EMT) in vivo and in vitro. The results demonstrated that BMSCs might enhance the invasive and metastatic potentials of breast cancer cells as a consequence of EMT induction through direct cell-to-cell contact. WSZG treatment remarkably suppressed motility, invasion, EMT-related gene, and protein markers in BMSC-conditioned breast cancer cells and ameliorated bone metastases and damages in nude mice following co-injection of BMSCs and MDA-MB-231BO breast cancer cells. Further investigation showed that the transforming growth factor-β1 (TGF-β1)/Smads pathway was an important mechanism enabling BMSCs to induce EMT occurrence of breast cancer cells. WSZG treatment reversed BMSC-induced EMT by downregulating TGF-β1/Smads signaling. Thus, WSZG extracts may be regarded as a potential antibone-metastatic agent for breast cancer therapy.

In this paper, we obtain the boundedness of commutators generated by singular integral operators and Lipschitz functions on amalgam spaces and weighted amalgam spaces.

Marine engines often use diesel as an alternative fuel to improve the economy. In recent years, waste oil, biodiesel and alcohol fuel are the most famous research directions among the alternative fuels for diesel. With the rapid development of the shipping industry, the air of coastal areas is becoming increasingly polluted. It is now necessary to reduce the emission of marine engines to meet the strict emission regulations. There are many types of alternative fuels for diesel oil and the difference of the fuel may interfere with the engine emissions; however, PM, HC, CO and other emissions will have a negative impact on SCR catalyst. This paper reviews the alternative fuels such as alcohols, waste oils, biodiesel made from vegetable oil and animal oil, and then summarizes and analyzes the influence of different alternative fuels on engine emissions and pollutant formation mechanism. In addition, this paper also summarizes the methods that can effectively reduce the emissions of marine engines; it can provide a reference for the study of diesel alternative fuel and the reduction of marine engine emissions.

Abstract Background Spinal cord injury (SCI) is one of the most severe central nervous system injuries. Currently, transplanting bone marrow mesenchymal stem cells (BMSCs) is considered a therapeutic option for SCI. Tanshinone IIA (TIIA) is one of the extracts obtained from Salvia miltiorrhiza Bunge, which has been shown to have some protective effects against SCI. The present research was aimed to explore whether TIIA would influence the fate of transplanted BMSCs in a rat model of SCI, especially with regard to their differentiation into neuronal cells. Methods Bone marrow mesenchymal stem cells were obtained from immature rats and identified using flow cytometry. After SCI, 1.0 × 107 cells labeled with PKH67 were transfused into the injured spinal cord. TIIA was first injected into the tail vein (30 mg/kg) 1 h before surgery. From day 1 to day 7 post-SCI, TIIA was injected (20 mg/kg) per day at the same time. Recovery of locomotor function and histological regeneration of the spinal cord were compared among the groups, with the differentiation and distribution of BMSCs determined anatomically and biochemically by the expression of neural cell markers. Results Locomotor assessments showed that the rats in the BMSCs + TIIA group exhibited higher scores (19.33 ± 0.58) than those in the other groups (13.67 ± 1.53, 17.67 ± 0.58, 18.00 ± 1.73). The area of the cavity in the BMSCs + TIIA rats was smaller than that in the other groups (1.30 ± 0.56, 10.39 ± 1.59, 6.84 ± 1.18, 4.36 ± 0.69). Co-expression of glial fibrillary acid protein was observed in transplanted BMSCs, with a reduced rate in the BMSCs + TIIA group relative to that in the SCI group. In contrast, the expression levels of Nestin, neuron-specific nuclear protein (NeuN) and neurofilament protein 200 (NF200) were greatest in the transplanted cells in the BMSCs + TIIA group. Conclusions Tanshinone IIA treatment enhances the therapeutic effects of BMSC transplant on SCI, likely by promoting the differentiation of neuronal cells.

Summary: Brown adipose tissue (BAT) is a thermogenic organ that maintains body temperature and energy homeostasis. Transcriptional regulation plays an important role in the program of brown adipogenesis. However, it remains unclear how the transcriptional events are controlled in this program. In this study, we analyze an SENP2 BAT conditional knockout mouse model and find that SENP2-mediated de-SUMOylation is essential for BAT development. SENP2 catalyzes de-SUMOylation of cAMP response element-binding protein (CREB) to suppress Necdin expression, which induces brown adipocyte differentiation and brown adipogenesis. Mechanistically, we find that SUMOylation enhances CREB interaction with serine/threonine protein phosphatase 2A (PP2A) to de-phosphorylate CREB, which activates Necdin transcription. SENP2 deficiency enhances the expression of Necdin to inhibit brown adipocyte differentiation. Therefore, we reveal a crucial role of SENP2-mediated de-SUMOylation of CREB in suppression of Necdin expression during brown adipose development and brown adipogenesis. : Liang et al. show that SENP2 suppresses Necdin expression, leading to brown adipocyte differentiation, which is essential for brown adipose tissue (BAT) adipogenesis. Keywords: SUMOylation, SENP2, brown adipogenesis, Necdin, CREB

Proteogenomics methods have identified many non-annotated protein-coding genes in the human genome. Many of the newly discovered protein-coding genes encode peptides and small proteins, referred to collectively as microproteins. Microproteins are produced through ribosome translation of small open reading frames (smORFs). The discovery of many smORFs reveals a blind spot in traditional gene-finding algorithms for these genes. Biological studies have found roles for microproteins in cell biology and physiology, and the potential that there exists additional bioactive microproteins drives the interest in detection and discovery of these molecules. A key step in any proteogenomics workflow is the assembly of RNA-Seq data into likely mRNA transcripts that are then used to create a searchable protein database. Here we demonstrate that specific features of the assembled transcriptome impact microprotein detection by shotgun proteomics. By tailoring transcript assembly for downstream mass spectrometry searching, we show that we can detect more than double the number of high-quality microprotein candidates and introduce a novel open-source mRNA assembler for proteogenomics (MAPS) that incorporates all of these features. By integrating our specialized assembler, MAPS, and a popular generalized assembler into our proteogenomics pipeline, we detect 45 novel human microproteins from a high quality proteogenomics dataset of a human cell line. We then characterize the features of the novel microproteins, identifying two classes of microproteins. Our work highlights the importance of specialized transcriptome assembly upstream of proteomics validation when searching for short and potentially rare and poorly conserved proteins.