Long-term cultivation reduces soil carbon storage by altering microbial network complexity and metabolism activity in macroaggregates.

Cultivation alters soil aggregation, microbial compositions and the potential for carbon sequestration in cropland soils. However, the specific effects of long-term cultivation and the underlying mechanisms on soil organic carbon (SOC) storage at different aggregate sizes remain poorly understood. We characterized the dynamics of SOC storage in macroaggregates (>0.25 mm) and microaggregates (<0.25 mm) across four paddy soils successively cultivated for 60, 100, 125, and 150 years. Microbial community compositions, network patterns, enzyme activities and carbon use efficiency (CUE) were examined to elucidate the underlying microbial pathways governing SOC storage. The results showed that prolonged cultivation led to an average reduction of 45 % in SOC storage, particularly in macroaggregates. Partial least squares path modeling revealed that shifts in microorganisms in macroaggregates explained almost 80 % of the variation in SOC storage. Specifically, variations in fungal composition and decreased complexity of microbial interaction networks were strongly correlated with SOC storage. Fungal community and microbial interactions also indirectly affected SOC storage by positively correlating with extracellular enzyme activity. Moreover, bacterial composition indirectly regulated SOC storage by positively correlating with carbon use efficiency. Our findings indicated that the macroaggregate-associated microbial interactions and the metabolism activities had significant implications for SOC sequestration in paddy fields. We suggest that implementation of management practices targeted at improvement of these microbial attributes could enhance agroecosystems sustainability.

APbI3-A2AgBiI6 Double-Layer Perovskite Film for a Self-Powered and High-Stability X-ray Detector.

The development of lead halide perovskite X-ray detectors has promising applications in medical imaging and security inspection but is hindered by poor long-term stability and drift of the dark current and photocurrent. Herein, we design a (Cs0.05MA0.65FA0.3)PbI3-(Cs0.1MA1.3FA0.6)AgBiI6 double-layer perovskite film to assemble a self-powered flat-panel X-ray detector. The demonstrated X-ray detector achieves an outstanding self-powered sensitivity of 80 µC Gyair-1 cm-2 under a 0 V bias. More importantly, owing to the inhibition of the phase transition process and ion migration of (Cs0.05MA0.65FA0.3)PbI3 by the (Cs0.1MA1.3FA0.6)AgBiI6 layer, the device exhibits excellent continuous operating stability with a retention rate of 99% dark current and photocurrent over X-ray pulses of up to 4000 s and excellent long-term stability without a loss of the original response current after 150 days in an air environment. The strategy of double-layer perovskites improves the stability and sensitivity of devices, which paves a path for the industrial application of lead halide perovskite X-ray detectors.

Comparative and phylogenetic analyses based on the complete chloroplast genome of Cornus subg. Syncarpea (Cornaceae) species.

This study presents a comprehensive analysis of the chloroplast (cp) genomes of Cornus species, including comparative and phylogenetic evaluations, as well as examinations of their genomic structure and composition. The cp genomes exhibit a typical circular quadripartite structure and demonstrate highly similar gene order and genomic structure. The complete cp genome size of the 10 taxa in this study is 156,965 bp to 157,383 bp, where the length of the large single-copy (LSC) region is 86,296 bp to 86,691 bp, small single-copy (SSC) region is 18,386 bp to 18,454 bp, and inverted repeat (IR) region is 23,143 bp to 26,112 bp. A total of 131 genes were found, including 86 protein-coding genes (PCGs), eight rRNA genes, and 37 tRNA genes. The mean GC content of the 10 taxa is 38.145%, where the LSC region is 36.396%, the SSC region is 32.372%, and the IR region is 43.076%. Despite the relatively conserved nature of the cp genome within the species of Cornus, 25-31 simple sequence repeats (SSRs) were identified in the 10 taxa in our study. The SSRs were found to be distributed in the LSC, SSC, and IR regions in Cornus hongkongensis subsp. hongkongensis, C. hongkongensis subsp. elegans, C. hongkongensis subsp. gigantea, and C. hongkongensis subsp. tonkinensis, while the SSR was not found in the IR region of the other six taxa. Thus, whole cp genomics is a valuable tool for species identification, taxonomic clarification, and genomic evolutionary analysis. Furthermore, our findings reveal that C. hongkongensis and C. hongkongensis subsp. gigantea, along with Cornus kousa and Cornus elliptica, form sister groups. Notably, C. hongkongensis subsp. ferruginea and C. hongkongensis subsp. melanotricha did not exhibit affinity with C. hongkongensis subsp. hongkongensis. Our study furnishes essential data for further research on their classification and provides novel insights into the relationship within Cornus subg. Syncarpea.

Co-Occurrence Patterns of Soil Fungal and Bacterial Communities in Subtropical Forest-Transforming Areas.

Soil microbial communities are engineers of important biogeochemical processes and play a critical role in regulating the functions and stability of forest ecosystem. However, few studies have assessed microbial interactions during forest conversion, which is essential to the understanding of the structure and function of soil microbiome. Herein, we investigated the co-occurrence network pattern and putative functions of fungal and bacterial communities in forest-transforming areas (five sites that cover the typical forests) using high-throughput sequencing of the ITS genes and 16S rRNA. Our study showed that the bacterial network had higher average connectivity and more links than fungal network, which might indicate that the bacterial community had more complex internal interactions compared with fungal one. Alphaproteobacteria_unclassfied, Telmatobacter, 0319-6A21 and Latescibacteria_unclassfied were the keystone taxa in bacterial network. For the fungal community network, the keystone taxon was Ceratobasidium. A structural equation model indicated that the available potassium and total organic carbon were important soil environmental factors, which affected all microbial modules, including bacterial and fungi. Total nitrogen had significant effects on the bacterial module that contains a relatively rich group of nitrogen cycling functions, and pH influenced the bacterial module which have higher potential functions of carbon cycling. And, more fungal modules were directly affected by forest structure (S Tree) compared with bacterial ones. This study provides new insights into our understanding of the feedback of underground creatures to forest conversion and highlights the importance of microbial modules in the nutrient cycling process.

POH1 facilitates pancreatic carcinogenesis through MYC-driven acinar-to-ductal metaplasia and is a potential therapeutic target.

Pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), a necessary process for pancreatic ductal adenocarcinoma (PDAC) initiation. However, the regulatory role of POH1, a deubiquitinase linked to several types of cancer, in ADM and PDAC is unclear. In this study, we investigated the role of POH1 in ADM and PDAC using murine models. Our findings suggest that pancreatic-specific deletion of Poh1 alleles attenuates ADM and impairs pancreatic carcinogenesis, improving murine survival. Mechanistically, POH1 deubiquitinates and stabilizes the MYC protein, which potentiates ADM and PDAC. Furthermore, POH1 is highly expressed in PDAC samples, and clinical evidence establishes a positive correlation between aberrantly expressed POH1 and poor prognosis in PDAC patients. Targeting POH1 with a specific small-molecule inhibitor significantly reduces pancreatic tumor formation, highlighting POH1 as a promising therapeutic target for PDAC treatment. Overall, POH1-mediated MYC deubiquitination is crucial for ADM and PDAC onset, and targeting POH1 could be an effective strategy for PDAC treatment, offering new avenues for PDAC targeted therapy.

Foldback-crRNA-Enhanced CRISPR/Cas13a System (FCECas13a) Enables Direct Detection of Ultrashort sncRNA.

The CRISPR/Cas13a system has promising applications in clinical small noncoding RNA (sncRNA) detection because it is free from the interference of genomic DNA. However, detecting ultrashort sncRNAs (less than 20 nucleotides) has been challenging because the Cas13a nuclease requires longer crRNA-target RNA hybrids to be activated. Here, we report the development of a foldback-crRNA-enhanced CRISPR/Cas13a (FCECas13a) system that overcomes the limitations of the current CRISPR/Cas13a system in detecting ultrashort sncRNAs. The FCECas13a system employs a 3'-terminal foldback crRNA that hybridizes with the target ultrashort sncRNA, forming a double strand that "tricks" the Cas13a nuclease into activating the HEPN structural domain and generating trans-cleavage activity. The FCECas13a system can accurately detect miRNA720 (a sncRNA currently known as tRNA-derived small RNA), which is only 17 nucleotides long and has a concentration as low as 15 fM within 20 min. This FCECas13a system opens new avenues for ultrashort sncRNA detection with significant implications for basic biological research, disease prognosis, and molecular diagnosis.

Ultrasound-enhanced catalytic hairpin assembly capable of ultrasensitive microRNA biosensing for the early screening of Alzheimer's disease.

Catalytic hairpin assembly (CHA) is a promising enzyme-free, isothermal signal amplification strategy, but the relatively time-consuming strand replacement limits its application scenarios. Here, we developed an ultrasound-enhanced catalytic hairpin assembly (UECHA) biosensing platform for early screening of Alzheimer's disease by introducing a portable acoustic-drive platform with functionalized microspheres for effective biomarkers enrichment and fluorescence enhancement. By constructing a gradient ultrasonic field in a microcavity, the platform concentrates the functionalized microspheres in a central position, accompanied by an enhanced fluorescence signal with a specific release. In addition, the programmable frequency modulation can also modify the acoustic potential well and effectively promote non-equilibrium chemical reactions such as CHA (25 min). Compared with the conventional catalytic hairpin assembly (CHA), UECHA allows for direct and quantitative measurement of AD miRNAs down to 3.55 × 10-15 M in 1 µL samples. This visual analysis of ultra-trace biomarkers based on acoustic enrichment and promotion provides a new perspective for the rapid and highly sensitive clinical detection of Alzheimer's disease.

RatioCRISPR: A ratiometric biochip based on CRISPR/Cas12a for automated and multiplexed detection of heteroplasmic SNPs in mitochondrial DNA.

Mitochondrial genetic diseases are often characterized by heteroplasmic single nucleotide polymorphisms (SNPs) where both wild-type (WT) and mutant-type (MT) coexist, making detection of accurate SNP abundance critical for diagnosis. Here, we present RatioCRISPR, an automated ratiometric biochip sensor based on the CRISPR/Cas12a system for detecting multiple heteroplasmic SNPs in mitochondrial DNA (mtDNA). The ratiometric sensor output is only influenced by the relative abundance of WT and MT, with minimal impact from sample concentration. Biochips allow the simultaneous detection of multiple SNP sites for more accurate disease diagnosis. RatioCRISPR can accurately detect 8 samples simultaneously within 25 min with a limit of detection (LOD) of 15.7 aM. We successfully detected 13 simulated samples of three mtDNA point mutations (m.3460G>A, m.11778G>A, and m.14484T>C), which lead to Leber's hereditary optic neuropathy (LHON) and set a threshold (60%) of heteroplasmy to evaluate disease risk. This automated and accurate biosensor has broad applications in diagnosing multiple SNPs, especially those with heteroplasmic variations, making it an advanced and convenient tool for mtDNA disease diagnosis.

Interactive Effects of Flooding Duration and Sediment Texture on the Growth and Adaptation of Three Plant Species in the Poyang Lake Wetland.

Flooding duration and sediment texture play vital roles in the growth and adaptation of wetland plants. However, there is a lack of research on the interactive effects of flooding duration and sediments on wetland plants. A two-factor experiment with flooding duration and sediment texture was designed in the study, involving three plant species commonly found in the Poyang Lake wetland (i.e., Carex cinerascens, Phalaris arundinacea, and Polygonum criopolitanum). Our findings were as follows: (i) Sediments play a crucial role in the growth and adaptation of hygrophilous plants, but they exhibited a weaker effect than flooding. (ii) Sediment texture mediates flooding to affect the stressing responses of wetland plant functional traits, including the leaf chlorophyll content, the plant height, and the number of leaves and ramets. (iii) Sediment texture forms interactive effects with flooding duration and directly influences hygrophilous plants. The results of this study help provide theoretical insights from a more scientific perspective for the prediction of hygrophilous plant dynamics and to facilitate the formulation of wetland management.

The transvaginal mesh class action: a tertiary teaching hospital experience of all mid-urethral sling procedures performed between 1999 and 2017.

INTRODUCTION AND HYPOTHESIS: Class action against Ethicon (J&J), manufacturer of transvaginal mesh devices, including mid-urethral slings (MUS), was brought to the Federal Court of Australia in 2016 by Shine Lawyers. As a result, subpoenas to all hospitals and networks were received, which overrode patient privacy concerns. This medical record search allowed a complete audit and communication with patients to offer clinical review. This enabled a review of complications, readmission and re-operation for women who underwent a MUS for stress urinary incontinence. METHODS: A cohort study of women who underwent MUS treatment for stress urinary incontinence (SUI) at a single tertiary teaching hospital between 1999 and 2017 was carried out. The main outcome measures were the rate of readmission and re-operation following MUS procedures. These include voiding dysfunction managed by sling loosening or sling division, mesh pain or exposure managed by mesh removal and reoperation for recurrent stress urinary incontinence. RESULTS: Between 1999 and 2017, a total of 1,462 women were identified as having a MUS; of these, 1,195 (81.7%) had full patient records available. Voiding dysfunction requiring surgical intervention with sling loosening or division was 3%, excision for mesh exposure was 2%, and partial or complete excision for pain was 1% at a median of 10 years from index surgery. The reoperation rate for recurrent stress urinary incontinence was 3%. CONCLUSION(S): This audit of all MUS procedures performed at a tertiary centre confirms an overall low rate of readmission for complications and recurrent SUI surgery; this justifies its continued availability with appropriate informed consent.

Species richness disparity in tropical terrestrial herbaceous floras: Evolutionary insight from Collabieae (Orchidaceae).

Species richness is spatially heterogeneous even in the hyperdiverse tropical floras. The main cause of uneven species richness among the four tropical regions are hot debated. To date, higher net diversification rates and/or longer colonization time have been usually proposed to contribute to this pattern. However, there are few studies to clarify the species richness patterns in tropical terrestrial floras. The terrestrial tribe Collabieae (Orchidaceae) unevenly distributes in the tropical regions with a diverse and endemic center in Asia. Twenty-one genera 127 species of Collabieae and 26 DNA regions were used to reconstruct the phylogeny and infer the biogeographical processes. We compared the topologies, diversification rates and niche evolutionary rates of Collabieae and regional lineages on empirical samplings and different simulated samplings fractions respectively. Our results suggested that the Collabieae originated in Asia at the earliest Oligocene, and then independently spread to Africa, Central America, and Oceania since the Miocene via long-distance dispersal. These results based on empirical data and simulated data were similar. BAMM, GeoSSE and niche analyses inferred that the Asian lineages had higher net diversification and niche evolutionary rates than those of Oceanian and African lineages on the empirical and simulated analyses. Precipitation is the most important factor for Collabieae, and the Asian lineage has experienced more stable and humid climate, which may promote the higher net diversification rate. Besides, the longer colonization time may also be associated with the Asian lineages' diversity. These findings provided a better understanding of the regional diversity heterogeneity in tropical terrestrial herbaceous floras.

D-mannose reduces adipogenesis by inhibiting the PI3K/AKT signaling pathway.

PURPOSE: To explore the effects and potential mechanisms of D-mannose on adipogenic differentiation of two kinds of representative mesenchymal stem cells (MSCs). METHODS: We cultured two kinds of representative MSCs, human adipose tissue-derived stromal cells (hADSCs) as well as human bone marrow mesenchymal stem cells (hBMSCs), with adipogenic-induced medium containing D-mannose or D-fructose as the control. Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB) were used to detect whether D-mannose had effects on adipogenic differentiation of MSCs. RNA sequencing (RNA-seq) transcriptomic analysis was further used to explore the potential mechanisms of D-mannose on adipogenic differentiation of MSCs. After that, qRT-PCR and WB were used to verify the results of RNA-seq. Last, we removed bilateral ovaries of female rats to establish an estrogen deficiency obesity model, and gave D-mannose intragastric administration. One month later, the femurs of rats were sliced for oil red O staining, and the inhibitory effect of D-mannose on lipid formation in vivo was studied. RESULTS: Oil red O staining, qRT-PCR and WB in vitro demonstrated that D-mannose inhibited the adipogenic differentiation of both hADSCs and hBMSCs. Oil red O staining of femur sections proved that D-mannose was able to reduce in vivo adipogenesis. The results of RNA-seq transcriptomic analysis revealed that the adipogenesis-inhibition effects of D-mannose were performed by antagonizing the PI3K/AKT signaling pathway. Besides, qRT-PCR and WB further verified the results of RNA-seq. CONCLUSION: Our study indicated that D-mannose was able to reduce adipogenic differentiation of both hADSCs and hBMSCs by antagonizing the PI3K/AKT signaling pathway. D-mannose is expected to be a safe and effective treatment strategy for obesity.

An aM-level sensitive cascade CRISPR-Dx system (ASCas) for rapid detection of RNA without pre-amplification.

The CRISPR/Cas system is known as one of the directions of the next generation of mainstream molecular diagnostic technology. However, most current CRISPR/Cas molecular diagnostics still rely on the pre-amplification of nucleic acid due to the limited sensitivity of CRISPR/Cas alone, which has no significant advantage over commercial Taqman-PCR and TwistAmp® Exo kits. Herein, we report an aM-level sensitive cascade CRISPR-Dx system (ASCas) that eliminates nucleic acid pre-amplification, thus avoiding aerosol contamination and greatly reducing the testing environment and personnel skill requirements for molecular diagnostics. Most importantly, the Cas13a nucleases with high sensitivity and trans-cleavage efficiency can rapidly cleaved RNA bubbles on the hybridized cascade probe at low concentration target RNA detection, which results in the destruction of the cascade probe and releases a large amount of trigger DNA for further signal amplification of secondary Cas12a reactions. Therefore, the ASCas system achieves amplification-free, ultra-sensitivity (1 aM), and ultra-fast (20 min) RNA detection. In addition, the ASCas system replaces the complicated screening process of primers and probes with the programmed Cas13a-crRNA design so that a suitable detection system can be constructed more quickly and straightforwardly for the mutation-prone SARS-CoV-2 virus.

A portable thermostatic molecular diagnosis device based on high-efficiency photothermal conversion material for rapid field detection of SARS-CoV-2.

The outbreak of the novel coronavirus (SARS-CoV-2) has seriously harmed human health and economic development worldwide. Studies have shown that timely diagnosis and isolation are the most effective ways to prevent the spread of the epidemic. However, the current polymerase chain reaction (PCR) based molecular diagnostic platform has the problems of expensive equipment, high operation difficulty, and the need for stable power resources support, so it is difficult to popularize in low-resource areas. This study established a portable (<300 g), low-cost (<$10), and reusable molecular diagnostic device based on solar energy photothermal conversion strategy, which creatively introduces a sunflower-like light tracking system to improve light utilization, making the device suitable for both high and low-light areas. The experimental results show that the device can detect SARS-CoV-2 nucleic acid samples as low as 1 aM within 30 min.

Association of caspase-1 gene polymorphisms with rheumatoid arthritis risk in a Chinese Han population.

The goals of present research are to investigate if the genetic polymorphisms in the caspase-1 (CASP1) gene are associated with the risk of rheumatoid arthritis (RA) and the clinical characteristics of the illness in Han patients from China. Our team studied the CASP1 rs2409062 A/G polymorphisms in 1095 healthy controls and 805 RA patients, while the genotype was identified via a custom-by-design 48-Plex single nucleotide polymorphism (SNP) scan™ Kit. The mRNA expression levels of the CASP1 in 40 RA cases and 40 healthy controls were detected by qRT-PCR, while blood plasma levels of the CASP1 in 40 RA cases and 40 paired controls measured via ELISA. Our research showed that the CASP1 rs2409062 A/G polymorphisms were related to an elevated risk for RA. By stratified analysis, our team discovered a remarkably elevated RA risk in females sufferers, age ≥ 55, CRP-positive, or DAS28 < 3.20. In contrast to the control group, the mean level of CASP1 protein in the plasma of RA cases rised significantly. Moreover, RA cases displayed significantly greater levels of CASP1 mRNA versus the control group (P < 0.05). Those outcomes reveal that the CASP1 rs2409062 A/G gene polymorphisms are associated with an elevated risk for RA in a Chinese Han population.

Enhanced Selectivity in the Electroproduction of H2 O2 via F/S Dual-Doping in Metal-Free Nanofibers.

Electrocatalytic two-electron oxygen reduction (2e- ORR) to hydrogen peroxide (H2 O2 ) is attracting broad interest in diversified areas including paper manufacturing, wastewater treatment, production of liquid fuels, and public sanitation. Current efforts focus on researching low-cost, large-scale, and sustainable electrocatalysts with high activity and selectivity. Here a large-scale H2 O2 electrocatalysts based on metal-free carbon fibers with a fluorine and sulfur dual-doping strategy is engineered. Optimized samples yield with a high onset potential of 0.814 V versus reversible hydrogen electrode (RHE), an almost ideal 2e- pathway selectivity of 99.1%, outperforming most of the recently reported carbon-based or metal-based electrocatalysts. First principle theoretical computations and experiments demonstrate that the intermolecular charge transfer coupled with electron spin redistribution from fluorine and sulfur dual-doping is the crucial factor contributing to the enhanced performances in 2e- ORR. This work opens the door to the design and implementation of scalable, earth-abundant, highly selective electrocatalysts for H2 O2 production and other catalytic fields of industrial interest.

Isoliquiritigenin from licorice flavonoids attenuates NLRP3-mediated pyroptosis by SIRT6 in vascular endothelial cells.

ETHNOPHARMACOLOGIC RELEVANCE: Licorice is a traditional Chinese medicine that has been used for cardiovascular diseases. Recent studies found that supplementation with licorice extracts attenuated the development of atherosclerosis (AS) in hypercholesterolemic patients. Many studies have shown that licorice flavonoids, the main active components of licorice, have a variety of pharmacological effects, including anti-inflammation, regulation of lipid metabolism, and antioxidation. However, the key active components against AS in licorice flavonoids are still unclear. AIM OF THE STUDY: The aim of this paper is to investigate the active components of licorice flavonoids that exert anti-atherosclerotic effects and the underlying mechanisms. MATERIALS AND METHODS: Network pharmacology was used to screen the active components of licorice flavonoids that have anti-atherosclerotic effects. Combining bioinformatics analysis and in vitro studies, the effects and underlying mechanisms of the active component isoliquiritigenin (ISL) on cell pyroptosis were further investigated in tumor necrosis factor (TNF)-α-treated human umbilical vein endothelial cells (HUVECs). RESULTS: We constructed a compound-target network and screened 3 active components, namely, ISL, glabridin, and naringenin in licorice flavonoids. The half maximal effective concentration values of these 3 components suggested that ISL was the key active component against TNF-α-induced endothelial cell injury. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that ISL could potentially treat AS via the nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathway. An in vitro study verified that ISL suppressed TNF-α-induced NLRP3 activation and pyroptosis in HUVECs. The molecular docking and cellular thermal shift assay showed good compatibility between ISL and class III histone deacetylase sirtuin 6 (SIRT6). Moreover, we found that ISL upregulated the expression of SIRT6 in TNF-α-treated HUVECs. Further study found that SIRT6 knockdown reduced the inhibitory effect of ISL on pyroptosis, whereas the NLRP3 inhibitor reversed this process in TNF-α-treated HUVECs. CONCLUSIONS: Our results demonstrate that ISL is a key active component of licorice flavonoids. ISL attenuates NLRP3-mediated vascular endothelial cell pyroptosis via SIRT6, and SIRT6 may be a potential target of ISL for the treatment of AS.

Bendamustine in the treatment of patients with indolent non-Hodgkin lymphoma refractory or relapse to rituximab treatment: An open-label, single-agent, multicenter study in China.

BACKGROUND: The optimal treatment strategy for refractory or relapse (R/R) indolent non-Hodgkin lymphoma (iNHL) has not been fully identified. This study aims to investigate the efficacy and tolerance of bendamustine hydrochloride developed in native Chinese corporation in the treatment of patients with R/R iNHL. METHODS: A total of 101 patients from 19 centers were enrolled in this study from July 2016 to February 2019. Bendamustine hydrochloride (120 mg/m2 ) was given on days 1 and 2 of each 21-day treatment cycle for six planned cycles or up to eight cycles if tolerated. Parameters of efficacy and safety were analyzed. RESULTS: The median age of the patients was 53.44 (range, 24.4-74.6) years old. A total of 56 (55.44%) patients completed at least six treatment cycles, and the relative dose intensity was 93.78%. The overall response rate was 72.28%, and the median duration of response was 15.84 months (95% confidence interval [CI], 13.77-27.48 months). Median progression-free survival was 16.52 months (95% CI, 14.72-23.41 months), and the median overall survival was not reached. Grade 3 or 4 hematologic toxicities included neutropenia (77.22%), thrombocytopenia (29.70%), and anemia (15.84%). The most frequent nonhematologic adverse events (any grade) included nausea, vomiting, fatigue, fever, decreased appetite, and weight loss. Seven patients died during the trial, and four cases may be related to the investigational drug. CONCLUSIONS: This study reveals that bendamustine hydrochloride is a feasible treatment option for the indolent B-cell non-Hodgkin lymphoma patient who has not remitted or relapsed after treatment with rituximab. All adverse events were predictable and manageable.

Concerns about Data Integrity of 22 Randomized Controlled Trials in Women's Health.

OBJECTIVE: During a review on postpartum hemorrhage, we identified randomized controlled trials (RCTs) of one author conducted at the same time and place for the same condition, with large differences in baseline characteristics. We assessed the data integrity of the RCTs of this author. STUDY DESIGN: We undertook a focused analysis of the data integrity of all RCTs published by Dr. Ahmed M. Maged. We examined the studies for clinical logic and made pairwise comparisons of baseline characteristics and outcomes between trials. We used mathematical methods to assess whether the distribution of baseline characteristics was compatible with chance. RESULTS: Between March 2015 and December 2019, Dr. Maged published 22 RCTs (n = 3,722). The median number of participants randomized per center per month was 32 (range = 1-89). Fifteen studies were either not or retrospectively registered, with one study registered 1 year after publication. One study was submitted for publication prior to the completion of the described study period. There were many unusual findings in the studies, including biologically implausible occurrences such as the absence of an association between gestational age and birthweight in seven studies and very different body mass index between three trials, which ran at the same time in the same hospital on the same topic as well as unlikely occurrences such as limited participant drop outs. One paper contained considerable text duplication and identical data to that in a paper published by a different author group from a different hospital, with both papers submitted at the same time. Mathematical analysis of the baseline characteristics of all 22 trials indicated that at least some of the reported baseline characteristics were unlikely to be the result of proper randomization. CONCLUSION: Our analyses of the 22 RCTs of Dr. Maged suggest potential data integrity issues in at least some of them. We suggest that journals investigate according to the Committee on Publication Ethics guidelines. The procedures demonstrated in this paper may help to assess data integrity in future attempts to verify the authenticity of published RCTs. KEY POINTS: · We identified a number of findings biologically implausible in RCTs by Maged.. · Monte Carlo simulation found pooled data of Maged RCTs were unlikely result of proper randomization.. · Textual overlap and almost identical data were found between a Maged paper and another paper.. · The methods we described may be useful for future efforts in validating scientific data integrity..

Study on the imbalance of M1/M2 macrophage polarization in severe chronic periodontitis.

BACKGROUND: Macrophages commonly exist in two distinct subsets in different microenvironments: classically activated macrophages (M1) and alternatively activated macrophages (M2). The imbalance of M1-M2 macrophage polarization is often related to various diseases or inflammatory states. OBJECTIVE: The purpose of this study was to determine whether there is an imbalance in the expression of M1 and M2 macrophage-related cytokines in severe chronic periodontitis. METHODS: A total of 30 clinical specimens, including severe chronic periodontitis tissues (n= 15) and healthy control tissues (n= 15), were used in this study. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot methods were used to detect the mRNA and protein expression levels of M1 macrophage-related cytokines (inducible nitric oxide synthase (iNOS) and signal transducer and activator of transcription 1 (STAT1)) and M2 macrophage-related cytokines (arginase-1 (Arg-1) and STAT6), respectively. RESULTS: The mRNA and protein expression levels of M1 macrophage-related cytokines (iNOS and STAT1) and M2 macrophage-related cytokines (Arg-1 and STAT6) were significantly increased in severe chronic periodontitis patients. In addition, the ratios of iNOS/Arg-1 and STAT1/STAT6 in the severe chronic periodontitis group were also significantly increased (P< 0.01). CONCLUSION: The imbalance of M1/M2 macrophages exists in the pathogenesis of severe chronic periodontitis, and has a tendency towards M1 polarization. Therefore, maintaining the immune balance of M1/M2 macrophages may be a novel therapeutic alternative for the management of severe chronic periodontitis.