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Post-transcriptional modification of RNA can contribute to regulating behavior. Here, the authors show that modulating the expression of Fto results in epitranscriptomic changes in the mouse hippocampus associated with depression-like behavior.

Abstract Background Vertigo and dizziness (VD) are among the most frequently seen symptoms in clinics and are important for medical students, especially for those in Chinese standardized residency training (SRT). The aim of our study was to examine the PAL method’s feasibility in the clinical teaching of VD-related diseases for SRT students in China. Methods This is a randomized, controlled, multicenter study. A total of 228 residents were invited to participate in this study, of which 198 completed the program. The students were randomized into two groups, and VD-related diseases were taught using lecture-based learning (control group) or peer-assisted learning (PAL). An examination paper and a rating scale were used to evaluate students’ performance in the mastery of VD-related theoretical knowledge and clinical skills, meanwhile students’ perceptions, satisfaction, and risk of burnout were also analyzed using a questionnaire. Independent-samples t-test and chi-square analysis were performed to evaluate statistical significance for continuous variables and categorical variables, respectively, using SPSS 18.0 software. Results The PAL group performed better in mastering theoretical knowledge and clinical skills than the control group. And more students believed that PAL could help improve their personal qualities such as teamwork skills. However, more students reported that PAL increased the risk of burnout. Conclusions PAL was a suitable and effective method in the clinical teaching of some specialized diseases, especially it was recommended for students who had gained initial knowledge and skills, such as Chinese SRT students. However, we should draw attention to the increased risk of burnout if PAL is intended to be widely used in clinical teaching. Trial registration ISRCTN registry, ISRCTN53773239 , 05/07/2021, retrospectively registered.

Pathologic protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells via extracellular vesicles or direct cell-to-cell contact. Here, Liu et al. show that viral glycoproteins can contribute to intercellular proteopathic seed transmission via both routes.

Abstract This paper proposes a novel distribution line parameter estimation method, driven by the probabilistic data fusion of the distributed phasor measurement unit (D‐PMU) and the advanced measurement infrastructure. The synchronized and high‐precision D‐PMU is utilized to tackle the challenge risen by the a‐synchronization of smart meters. Correspondingly, a time‐alignment algorithm is proposed to obtain the time‐synchronous error (TSE) dataset for the up‐stream smart meter. The non‐parametric estimation method is performed then to evaluate the probabilistic density curve of TSE. Furthermore, TSE data of down‐stream smart meters are generated by implementing the acceptance‐rejection process based on the obtained probabilistic density curve. Leveraging the generated TSE dataset, a new time‐shifted D‐PMU curve is probabilistically aligned or fused with the down‐stream advanced measurement infrastructure curves. According to the complete voltage drop model, the line parameter estimation of resistance and reactance is formulated as a quadratic programming problem and solved by Optimal Toolbox in MATLAB by conducting multi‐run Monte‐Carlo simulations under various scenarios. Simulation results demonstrate the effectiveness and robustness of the proposed methodology.

BackgroundExtramedullary plasmacytoma (EMP) is a localized plasma cell neoplasm that originates from tissues other than bone. The survival trends and prognostic factors of patients with EMP in recent years remain unreported.MethodsWe used the SEER databases to extract the data. Survival curves were calculated using the Kaplan-Meier method and a nomogram was created based on the Cox’s proportional hazards model.ResultsA total of 1676 cases of EMP were identified. Patients in period-2 (2008-2016) show similar survival (p=0.8624) to those in period-1(1975-2007). Age, gender, race, and sites were prognostic of patient outcomes. And the use of surgery was associated with improved survival. The patients were randomly assigned to the training cohort and the validation cohort in a ratio of 2:1. Four factors including age, gender, race, and sites were identified to be independently predictive of the overall survival of patients with EMP. A prognostic model (EMP prognostic index, EMP-PI) comprising these four factors was constructed. Within the training cohort, three risk groups displayed significantly different 10-year survival rates: low-risk (73.0%, [95%CI 66.9-78.2]), intermediate-risk (39.3%, [95%CI 34.3-44.3]), and high-risk (22.6%, [95%CI 15.3-30.9]) (p

Urolithin A (UA) has received considerable research attention because of its health benefits. However, only a few strains have been reported to produce UA from ellagic acid (EA), and the molecular mechanisms underlying the gut microbiota-mediated transformation of ellagic acid into urolithin A is limited. In the present study, a single strain FUA027 capable of converting ellagic acid into UA in vitro was isolated from the fecal samples. The strain was identified as Enterococcus faecium through the morphological, physiological, biochemical and genetic tests. UA was produced at the beginning of the stationary phase and its levels peaked at 50 h, with the highest concentration being 10.80 μM. The strain Enterococcus faecium FUA027 is the first isolated strain of Enterococcus sp. producing urolithin A from ellagic acid, which may be developed as probiotics and used to explore molecular mechanisms underlying the biotransformation of ellagic acid into UA.

Photoperiod responsiveness is important to soybean production potential and adaptation to local environments. Varieties from temperate regions generally mature early and exhibit extremely low yield when grown under inductive short-day (SD) conditions. The long-juvenile (LJ) trait is essentially a reduction and has been introduced into soybean cultivars to improve yield in tropical environments. In this study, we used next-generation sequencing (NGS)-based bulked segregant analysis (BSA) to simultaneously map qualitative genes controlling the LJ trait in soybean. We identified two genomic regions on scaffold_32 and chromosome 18 harboring loci LJ32 and LJ18, respectively. Further, we identified LJ32 on the 228.7-kb scaffold_32 as the soybean pseudo-response-regulator gene Tof11 and LJ18 on a 301-kb region of chromosome 18 as a novel PROTEIN FLOWERING LOCUS T-RELATED gene, Glyma.18G298800. Natural variants of both genes contribute to LJ trait regulation in tropical regions. The molecular identification and functional characterization of Tof11 and LJ18 will enhance understanding of the molecular mechanisms underlying the LJ trait and provide useful genetic resources for soybean molecular breeding in tropical regions.

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a major bacterial pathogen that causes hospital- and community-acquired infections. Owing to its multidrug resistance, it is imperative to develop new antimicrobial agents to treat MRSA infections. In this study, using genome mining analysis and a culture-based screening method to detect bacteriocin activity, we screened a strain, Bacillus sp. TL12, which harbored a putative leaderless bacteriocin gene cluster (bac gene cluster) and exhibited potent anti-MRSA activity. The antimicrobial agents, products of the bac gene cluster, were purified and identified as four novel leaderless bacteriocins: bacin A1, A2, A3, and A4. Bacin A2 was evaluated as a representative antimicrobial agent and showed remarkable antimicrobial activity against S. aureus, MRSA, and the foodborne pathogens Listeria monocytogenes and Bacillus cereus. Mechanistic experiments revealed that bacin A2 damaged cell membranes and exhibited bactericidal activity against MRSA. Bacin A2 effectively inhibited the formation of S. aureus and MRSA biofilms (>0.5× MIC) and killed the cells in their established biofilms (>4× MIC). The hemolytic and NIH/3T3 cytotoxicity assay results for bacin A2 confirmed its biosafety. Thus, bacins have potential as alternative antimicrobial agents for treating MRSA infections. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen that is difficult to treat because of its resistance to several widely used antibiotics. The present study aimed to identify novel anti-MRSA bacteriocins in a prominent producer of bacteriocins, Bacillus cereus group. Four novel leaderless bacteriocins, bacin A1, A2, A3, and A4, which show potent bactericidal effect against S. aureus and MRSA, were identified in Bacillus sp. TL12. Moreover, bacins inhibited biofilm formation and killed cells in the established biofilms of S. aureus and MRSA. These findings suggest that bacins are promising alternatives to treat MRSA infections.

Chitooligosaccharides (COS), a high-value chitosan derivative, have many applications in food, pharmaceuticals, cosmetics and agriculture owing to their unique biological activities. Chitosanase, which catalyzes the hydrolysis of chitosan, can cleave β-1,4 linkages to produce COS. In this study, a chitosanase-producing Bacillus paramycoides BP-N07 was isolated from marine mud samples. The chitosanase enzyme (BpCSN) activity was 2648.66 ± 20.45 U/mL at 52 h and was able to effectively degrade chitosan. The molecular weight of purified BpCSN was approximately 37 kDa. The yield and enzyme activity of BpCSN were 0.41 mg/mL and 8133.17 ± 47.83 U/mg, respectively. The optimum temperature and pH of BpCSN were 50 °C and 6.0, respectively. The results of the high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) of chitosan treated with BpCSN for 3 h showed that it is an endo-chitosanase, and the main degradation products were chitobiose, chitotriose and chitotetraose. BpCSN was used for the preparation of oligosaccharides: 1.0 mg enzyme converted 10.0 g chitosan with 2% acetic acid into oligosaccharides in 3 h at 50 °C. In summary, this paper reports that BpCSN has wide adaptability to temperature and pH and high activity for hydrolyzing chitosan substrates. Thus, BpCSN is a chitosan decomposer that can be used for producing chitooligosaccharides industrially.

Ascophyllum nodosum, a brown algae abundantly found along the North Atlantic coast, is recognized for its high polysaccharide content. In this study, we investigated the anti-hyperlipidemic effect of fucoidans derived from A. nodosum, aiming to provide information for their potential application in anti-hyperlipidemic therapies and to explore comprehensive utilization of this Iceland brown seaweed. The crude fucoidan prepared from A. nodosum was separated using a diethylethanolamine column, resulting in two fucoidan fractions, AFC-1 and AFC-2. Both fractions were predominantly composed of fucose and xylose. AFC-1 exhibited a higher sulfate content of 27.8% compared to AFC-2 with 17.0%. AFC-2 was primarily sulfated at the hydroxy group of C2, whereas AFC-1 was sulfated at both the hydroxy groups of C2 and C4. To evaluate the anti-hyperlipidemic effect, a hyperlipidemia mouse model was established by feeding mice a high-fat diet. The effects of AFC-1, AFC-2, and the crude extract were investigated, with the drug atorvastatin used as a positive comparison. Among the different fucoidan fractions and doses, the high dose of AFC-2 administration demonstrated the most significant anti-hyperlipidemic effect across various aspects, including physiological parameters, blood glucose levels, lipid profile, histological analysis, and the activities of oxidative stress-related enzymes and lipoprotein-metabolism-related enzymes (p < 0.05 for the final body weight and p < 0.01 for the rest indicators, compared with the model group), and its effect is comparable to the atorvastatin administration. Furthermore, fucoidan administration resulted in a lower degree of loss in gut flora diversity compared to atorvastatin administration. These findings highlight the significant biomedical potential of fucoidans derived from A. nodosum as a promising therapeutic solution for hypolipidemia.

Curved structures are used in many engineering applications. Temperature affects the performance of structural vibration and acoustics and can damage the equipment when its effects are severe. A theoretical model of the sound transmission loss (STL) of a simply supported curved plate considering the effect of temperature was established. Moreover, a numerical solution was obtained using the modal superposition method. The finite element results were compared to validate the theoretical model. The effects of temperature and acoustic loading on the modal frequency and STL were considered, and the variation laws of the radius of curvature, opening angle, and loss factor on the STL were analyzed. The results showed that the modal frequency increased with decreasing temperature, the frequency ratio of the same-order modal frequency varied approximately linearly with temperature, and the trough of the STL shifted toward high frequencies. The pitch angle substantially influenced the STL, whereas the azimuth angle was negligible. A larger radius increased the effect of temperature. In addition, an increase in the opening angle formed an aggregation of STL at (1, 1)-order modal frequencies. The loss factor affects only the amplitude of the trough position of the STL. Therefore, the proposed theoretical model can aid in the vibroacoustic design of curved plates in a thermal environment.

The authors present a method for the conversion of full-length tau protein into seeding-competent amyloid fibrils without heparin or other negatively charged co-factors, which could be useful for studying the effects of post-translational modifications on Tau aggregation as well as to identify potential inhibitors of tau aggregation. Biochemical experiments and solid-state NMR spectroscopy measurements show that these co-factor-free tau fibrils have similar properties as amyloid fibrils isolated from brain tissue but differ from those of commonly used heparin-induced tau fibrils.

High-fat diets (HFDs) are related to the incidence of obesity and diabetes, but the effect of high-fat diet-induced brain damage remains to be clarified. In our study, we found that 24 weeks of a HFD effectively induced obesity and a change in fur color in mice. In addition, the mice also exhibited deficits in learning and memory. We further found that autophagic flux was impaired in mice after HFD feeding. Hypoxia-inducible factor 1α (HIF-1α) expression was significantly increased in HFD-fed mice, and HFD feeding inhibited adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and induced mechanistic target of rapamycin (mTOR) phosphorylation and p70S6K expression. Treatment of HFD-induced BV2 cell model with palmitic acid (PA) was used to further verify a similar result. We concluded that improving tissue hypoxia or enhancing autophagy through the AMPK/mTOR/p70S6K pathway may be a relevant strategy for improving obesity- and ageing-related disorders.

Objective: The purpose of this study was to analyze the stability and instrument-related complications associated with fixation of the lumbar spine using the Short-Rod (SR) technique.Methods: Using finite element analysis, this study assessed the stability of a bilateral lumbar fixation system when inserting the pedicle screws at angles of 10°, 15°, and 20° to the endplate in the sagittal plane. Using the most stable construct with a screw angle, the model was then assessed with different rod lengths of 25, 30, 35, and 45 mm. The optimal screw inclination angle and rod length were incorporated into the SR model and compared against traditional parallel screw insertion (pedicle screws in parallel to the endplate, PPS) in terms of the stability and risk of instrument-related complications. The following parameters were evaluated using the validated L4–L5 lumbar finite element model: axial stiffness, range of motion (ROM), stress on the endplate and facet joint, von-Mises stress on the contact surface between the screw and rod (CSSR), and screw displacement.Results: The results showed that the SR model with a 15° screw inclination angle and 35 mm rod length was superior in terms of construct stability and risk of complications. Compared to the PPS model, the SR model had lower stiffness, lower ROM, less screw displacement, and lower stress on the facet cartilage, the CSSR, and screws. However, the SR model also suffered more stress on the endplate in flexion and lateral bending.Conclusion: The SR technique with a 15° screw inclination and 35 mm rod length offers good lumbar stability with a low risk of instrument-related complications.

Objectives: To examine associations between maternal sulfur dioxide (SO2) exposure and congenital ear malformations risk in offspring.Methods: We surveyed 1676 cases with congenital ear malformations and 7950 controls from the Maternal and Child Health Certificate Registry of Liaoning Province between 2010 and 2015. SO2 concentrations were obtained from the Municipal Environment Protection Bureau of Liaoning Province. Multivariable logistic regression models and Restricted cubic splines (RCS) model were used to assess the aforementioned association.Results: There were significant associations between maternal SO2 exposure and congenital ear malformations risk during the 3 months before conception (OR Q4 vs. Q1 = 1.93, 95% CI = 1.43–2.59) and the 3 months after conception (OR Q4 vs. Q1 = 1.63, 95% CI = 1.22–2.18). Similar results were obtained in the analysis of single-month exposure windows, except for the third month before conception and the third month after conception. Moreover, these findings were broadly consistent across subgroups and robust in sensitivity analyses. There were non-linear dose-response associations between SO2 exposure and congenital ear malformations based on restricted cubic spline model analysis.Conclusion: Maternal SO2 exposure is associated with increased congenital ear malformations risk in offspring.

The prediction of photovoltaic power generation is helpful to the overall allocation of power planning departments and improves the utilization rate of photovoltaic power generation. Therefore, this study puts forward an ultra-short-term power forecasting model of a photovoltaic power station based on modal decomposition and deep learning. The methodology involved taking the data of a 50 MW photovoltaic power generation system in the Inner Mongolia Autonomous Region as a sample. Furthermore, the weather conditions were classified, and the historical power data were decomposed into multiple VMF subcomponents and residual terms by the VMD method. Then, the residual term was decomposed twice by the CEEMDAN method. All subcomponents were sent to the LSTM network for prediction, and the predicted value of the photovoltaic power station was obtained by superimposing the subcomponent prediction results. ARIMA, SVM, LSTM, and VMD-LSTM models were built to compare the accuracy with the proposed models. The results revealed that the prediction accuracy of a non-combination forecasting model was limited when the weather suddenly changed. The VMD method was used to decompose the residual term twice, which could fully extract the complex data information in the residual term, and when compared with the VMD-LSTM model, the eRMSE, eMAPE, and eTIC of the VMD-CEEMDAN-LSTM model were reduced by 0.104, 16.596, and 0.038, respectively. The second decomposition technology has obvious prediction advantages. The proposed quadratic modal decomposition model effectively improves the precision of ultra-short-term prediction of photovoltaic power plants.

The diet of prehistoric humans in the Qijia period (4,400–3,500 BP) was significantly changed by the advent of dry agriculture and food globalization. However, it is yet to be proven whether wild plants were exploited despite the cultivation of millet, and whether wheat crops, cattle, and sheep originating from southwestern Asia were adopted into the regional human diet. This study presents stable isotope, starch grain, and phytolith analyses of 24 human teeth from the Lajia site in Qinghai, which is a representative Qijia culture settlement site. The carbon and nitrogen isotope results show that the subjects primarily ate C4 plants and had a high protein diet. Starch grain and phytolith results showed that the inhabitants consumed broomcorn millet (Panicum miliaceum), foxtail millet (Setaria italica), Triticeae, tubers and roots, along with other Pooideae and Poaceae plants. This data proves that although broomcorn and foxtail millet formed the mainstay of the Qijia diet, it also included a wide range of plants, such as the tribe Triticeae, tubers and roots, which would have been foraged rather than grown. Compared with the other three contemporaneous sites in Northern China, the proportion of millet starches was highest at the Lajia site, while the type and proportion of foraged plants were the lowest. This was probably because of the arid environment in the region, which could not have supported sufficient plant resources for foraging, which in turn might have led to enhanced millet cultivation and/or a greater reliance on hunting. No wheat or barley traces were found in human teeth in Lajia, and the high proportion of nitrogen was possibly related to the consumption of sheep because sheep bones were found in a zooarchaeological study. This study enhances our understanding of the subsistence strategies present in Qijia culture and of prehistoric food globalization, which is of pivotal significance for a deeper understanding of interactions between east and west Asia during the Neolithic and Bronze ages.

Abstract Urban flooding can be predicted by using different modeling approaches. This study considered different methods of modeling the dynamic flow interactions between pipe systems and surface flooding in urban areas. These approaches can be divided into two categories based on surface runoff collection units. This paper introduces a new hydrodynamic model that couples the storm water management model and the 2D overland model. The model’s efficiency was validated based on the aforementioned experimental dataset; agreement was verified by correlation values above 0.6. Additionally, this study used different approaches and compared their accuracy in predicting flooding patterns. The results show that the use of sub-catchments to model the collection of surface runoff was not predictive of the inundation process, indicating a lower goodness of fit with the recorded values than that of adopting cells. Moreover, to determine which method of adopting cells to collect runoff could better predict rainstorm-induced inundation, an error and correlation analysis was conducted. The analysis found low error and high correlation, suggesting that inundation can be effectively predicted by the new approaches. Ultimately, this study contributes to existing work on numerical analysis of the interaction methods of urban flooding.

ABSTRACT Objective: To determine sonographic features of malignancy in partially cystic thyroid nodules and assess the diagnostic efficacy of these features for differentiating between benign and malignant lesions in the nodules with indeterminate cytology. Subjects and methods: From January 2016 to December 2017, a total of 91 patients with 94 partially cystic thyroid nodules who had undergone ultrasound-guided fine-needle aspiration biopsy and thyroid surgery in our hospital were included in this study. The sonographic features of the thyroid nodules were analyzed to identify the predictive features of malignancy and assess the diagnostic efficacy of these features. Results: The features of hypoechogenicity, microcalcification, composition, and an eccentric solid component with an acute angle had statistically significant associations with malignant nodule (p

Northern Shaanxi is important in understanding the ancient use and northward spread of foxtail millet (Setaria italica) and broomcorn millet (Panicum miliaceum). Nonetheless, due to the lack of millet remains, AMS radiocarbon data, and environmental background, the emergence, crop structure, and environmental factors of millet use in northern Shaanxi remain ambiguous. To address this knowledge gap, a systematic survey was conducted along the Beiluo River. Forty-two relic units at 19 Neolithic sites were selected for analysis through phytolith, AMS radiocarbon dating, and spatio-temporal approaches. Phytolith and AMS radiocarbon dating analyses traced the utilization of millets in the Beiluo River to 6280 cal. BP. In addition, broomcorn millet was more prevalent than foxtail millet during the Neolithic period, although the prevalence of the latter increased during the late Longshan period. Spatio-temporal analysis demonstrated that millets initially appeared in the Beiluo River during the Yangshao period, gradually moving away during the Longshan period, which was probably first related to the nearest rivers and then the spread of cattle and sheep. However, the millet cultivation altitude remained at 1400 m throughout the Yangshao and Longshan periods. Collectively, these findings provide evidence for the use and northward spread of millets in northwest China.

Fucoidanase is an unstable enzyme with high specificity that requires a large about of time to screen it from microorganisms. In this study, enzymatic hydrolysis was used to produce low-molecular-weight fucoidan from microorganisms via the degradation of high-molecular-weight fucoidan without damage to the sulfate esterification structure of oligosaccharide. The microbial strain HN-25 was isolated from sea mud and was made to undergo mutagenicity under ultraviolet light. Fucoidanase was extracted via ultrasonication and its enzymatic activity was improved via optimization of the ultrasonic conditions. The enzymatic properties and degradation efficiency of fucoidanase were characterized. The microbial strain HN-25 is a Gram-negative aerobic and rod-shaped-cell bacterium, and therefore was identified as Cobetia amphilecti via 16s rDNA. The results proved that fucoidanase is a hydrolytic enzyme with a molecular weight of 35 kDa and with high activity and stability at 30 °C and pH 8.0. The activity of fucoidanase was significantly enhanced by sodium and calcium ions and inhibited by a copper ion and ethylenediaminetetraacetate (EDTA). There was a significant decrease in the molecular weight of fucoidan after enzymatic hydrolysis. The low-molecular-weight fuicodan was divided into four fractions, mainly concentrated at F3 (20~10 kDa) and F4 (≤6 kDa). These consequences suggest that fucoidanase obtained from Cobetia amphilecti is stable and efficient and could be a good tool in the production of bioactive compounds.

VPS33B is reported to be a tumor suppressor in hepatocellular carcinoma, nasopharyngeal carcinoma, colon cancer, and lung adenocarcinoma. Here, we observed that reduced VPS33B protein level was an unfavorable factor that promoted the pathogenesis of non-small cell lung cancer (NSCLC) in clinical specimens. We achieved lentivirus-mediated stable overexpression of VPS33B in NSCLC cells. Increased VPS33B reduced cell cycle transition and cell proliferation of NSCLC cells in vivo and in vitro. Knocking down VPS33B restored cell growth. Mechanism analysis indicated that miR-192-3p was induced by VPS33B and acted as a tumor suppressor of cell growth in NSCLC. Further, c-Myc or p53 was identified as a transcription factor that bound to the miR-192-3p promoter and regulated its expression. miR-192-3p directly targeted cell cycle-promoted factor CCNB1 and suppressed NSCLC cell growth. VPS33B modulated c-Myc/p53/miR-192-3p signaling to target CCNB1 by reducing activation of the Ras/ERK pathway. Our study reveals a novel molecular basis for VPS33B as a tumor suppressor to participate in the pathogenesis of NSCLC.

Abstract Background Chest keloids often converged into a large lesion on the chest in some patients. Such keloids often lead to obstacle to excision and reconstruction. We describe a surgical method for large chest keloids with expanded parasternal intercostal perforator flap (EPIPF). Methods Fifteen patients with chest keloid were treated with EPIPF in our department between August 2017 and Dec 2019. The surgical treatment was divided into two different phases. In the first phase, we implanted skin expanders into the layer under the deep fascia beside the keloids. The expander was expanded every week for about 3–4 months. In the second phase, the expander was removed, the keloid tissue was removed and an expanded perforator flap was then designed to cover the wound. Patients were followed-up after surgery. Complications after surgery were analyzed. Recurrence and the patients, satisfactory rate was recorded. Results Of the 15 patients, one patient complicated with undesirable small area wound healing. 11 were cured without scar hypertrophy or recurrence and four were partially cured with a small portion of scar hypertrophy. Eleven patients thought that the esthetic result was good (73.7%), and 4 patients thought the result was acceptable (26.7%). None patient was dissatisfied. Conclusion EPIPF are effective surgical method for managing large chest keloids. It can offer enough skin flap coverage for keloid wound resurfacing with stable blood supply to assure satisfactory results. Level of evidence Level IV, case series.

Quercetin is a widely-occurring flavonoid that protects against cancer, and improves memory and cardiovascular functions. However, whether quercetin exhibits therapeutic effects in diabetic retinopathy remains unclear. In this study, we established a rat model of streptozocin-induced diabetic retinopathy. Seventy-two hours later, the rats were intraperitoneally administered 150 mg/kg quercetin for 16 successive weeks. Quercetin markedly increased the thickness of the retinal cell layer, increased the number of ganglion cells, and decreased the overexpression of the pro-inflammatory factors interleukin-1β, interleukin-18, interleukin-6 and tumor necrosis factor-α in the retinal tissue as well as the overexpression of high mobility group box-1 and the overactivation of the NLRP3 inflammasome. Furthermore, quercetin inhibited the overexpression of TLR4 and NF-κBp65, reduced the expression of the pro-angiogenic vascular endothelial growth factor and soluble intercellular adhesion molecule-1, and upregulated the neurotrophins brain-derived neurotrophic factor and nerve growth factor. Intraperitoneal injection of the heme oxygenase-1 inhibitor zinc protoporphyrin blocked the protective effect of quercetin. These findings suggest that quercetin exerts therapeutic effects in diabetic retinopathy possibly by inducing heme oxygenase-1 expression. This study was approved by the Animal Ethics Committee of China Medical University, China (approval No. 2016PS229K) on April 8, 2016.

Hollow-core negative-curvature fibres have been the focus of current research, but how to reduce the loss of hollow-core negative-curvature fibres is a serious problem. This paper proposes a new structure of hollow-core negative-curvature fibres, that is numerically simulated using the finite-element method, and compared with the simulation results of hollow-core conjoined-tube negative curvature fibres (CTNCFs) and hollow-core nested anti-resonant nodeless fibres (NANFs). The results show that, the LP01 mode loss can reach 0.003694 dB/km with a transmission wavelength of 1.06 μm, the LP11 mode loss can be as low as 0.28423 dB/km, and the bending loss is 0.4405 dB/km with a bending radius of 5 cm and a transmission wavelength of 1.06 μm. The loss is reduced by an order of magnitude compared to CTNCFs and NANFs.

Abstract Solitary plasmacytoma of bone (SPB) is a single, isolated plasmacytoma originated from the bone. The survival trends of patients with SPB in recent years remain unknown. And the prognostic system of SPB may also need to be refined. The 18 Surveillance, Epidemiology, and End Results (SEER) databases of the National Cancer Institute in the United States were used to extract data for this study. The third edition of the International Classification of Disease for Oncology (ICD‐O‐3) code 9731 was used to identify cases of SPB. For each case, factors including age at the time of diagnosis, sex, race, marital status, insurance status, primary sites of tumors, and the use of surgery were collected. The outcomes of patients with SPB were compared between two groups. And the prognostic impacts of baseline characteristics and use of surgery was studied. A total of 4103 (from 1976 to 2016) cases of SPB were identified. The median age was 65 years old. Patients in time period‐2 (2008–2016) show better survival as compared to those in time period‐1(1976–2007) (median overall survival: 88 months vs. 73 months, p = 0.0332). Age ≤ 65 years and being male were associated with better outcomes. The widowed individuals had significantly inferior survival and myeloma‐specific survival than the single, married, or divorced individuals (p values all

With the access to a large number of intermittent and fluctuating new energy sources in the low-voltage distribution network, the complex relationship between producers and consumers makes the node voltage stability and other problems in the power system increasingly prominent. Aiming at the voltage stability problem caused by the intermittent and fluctuation of the new power system, based on the high-precision measurement data of PMU, this article used the model predictive control algorithm to realize regional voltage optimization and improve the stability of node voltage. First, the voltage sensitivity matrix is calculated using PMU measurement data and grid structure state information. Second, active power, reactive power, and voltage were taken as the input of the MPC algorithm, and the optimal compensation voltage instruction was obtained by rolling optimization, and the node voltage was compensated by SVG and SVC. Finally, a simulation experiment was carried out on the MATLAB/Simulink simulation platform, and the experimental results verified the correctness and effectiveness of the proposed control method.

As a common-used pothole repairing material, cold mix patching asphalt (CMA) has been widely used in practice. This article aims to develop a novel CMA with good overall performance and better environmental-friendliness. A few environmental-friendly ingredients, including a modifier named Usual-temperature Synthetic Pitch (USP), polyester-basalt composite fibers, a commercial anti-stripping agent, a commercial tackifier and biodiesel, were utilized for preparing Fiber-reinforced USP modified CMAs (FUAs). Laboratory tests, including workability assessment tests, Marshall stability tests, boiling water tests, rolling sieve cohesion tests, freeze-thaw splitting tests, wheel tracking tests and three-point bending tests, etc. were conducted to evaluate the workability, Marshall stability, adhesion, moisture susceptibility, rutting resistance, bending resistance and storage stability. Two mix designs of the cutback (termed as Scheme 1 and 2) with weight ratios of 100:6:18:0.3:0.6 and 100:6:20:0.4:0.8 for binder: USP: biodiesel: anti-stripping agent: tackifier were considered. Effect of fiber content (0.2%, 0.3%, 0.4% and 0.5% by aggregate weight) was also investigated considering an optimal polyester to basalt fiber weight ratio of 3:2. The results show that the optimal fiber content is 0.4%. The engineering properties of FUAs meet the construction requirements, and they also present good storage stability. Scheme 2-based cutback shows better workability, smaller penetration and better binder-aggregate adhesion than the Scheme 1-based cutback; consequently, the Scheme 2-based FUA presents advantages over Marshall stability, rutting resistance and bending resistance. Compared with Styrene-Butadiene-Styrene (SBS) modified CMAs, FUAs possess better overall performance and advantages over environmental conservation. The FUAs, therefore, have good application prospects in pavement repair.

Evidence of the association between maternal sulfur dioxide (SO2) exposure and the risk of omphalocele is limited and equivocal. We aimed to assess the aforementioned topic during the first trimester of pregnancy. A population-based case-control study was carried out in infants consisting of 292 cases of omphalocele and 7,950 healthy infant controls. Exposure to SO2, particulate matter with aerodynamic diameters ≤ 10 μm, and nitrogen dioxide was assessed by averaging the concentration from all stations in the mother's residential city. SO2 exposure was categorized into three groups, with the lowest tertile defined as the reference category. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression models. Higher SO2 exposure during the first trimester was significantly associated with omphalocele risk [per standard deviation (42 ug/m3) increment: OR = 1.39, 95% CI = 1.22–1.65]. When focusing on shorter exposure windows, similar positive associations were observed for SO2 exposure in the first and third months of pregnancy. In addition, compared with the lowest tertile, high SO2 exposure in the second month of pregnancy increased the risk of omphalocele (OR = 2.80, 95% CI = 1.61–4.97). Maternal exposure to SO2 during the first trimester may increase the risk of omphalocele in offspring.

Medical wound dressing with natural antibacterial efficacy is an important issue. However, few studies on Artemisia argyi oil based wound dressing have been studied because of the volatility of the Artemisia argyi oil. In this study, Artemisia argyi oil -microcapsules (AAO-MC)/PVC fibrous membrane were fabricated through emulsification-internal gelation and electrospinning method. The membranes were characterized by SEM, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and particle diameter, hydrophilicity, breathability, water vapor transmission rate (WVTR), and antibacterial performance were evaluated. The results show that AAO-MC microcapsules excellent stability, and the slow-release property. Moreover, the prepared AAO-MC/PVC fibrous membrane indicated good WVT (72.47 g/(m²·h)), high hydrophilicity (30.5°), and outstanding antibacterial rate (94.3%). This study provides a new strategy to prepare microcapsule nanofibrous membrane with excellent performance and is suggested to be a promising candidate for medical wound dressings.

Abstract Aims/Introduction To assess the efficacy and safety of metformin/sitagliptin‐based dual/triple therapy in elderly Chinese patients with type 2 diabetes mellitus. Materials and Methods This subgroup analysis included individuals aged ≥65 years from the STRATEGY study, a two‐stage study in which type 2 diabetes mellitus patients with unsatisfactory glycemic control on metformin were first treated with the dual combination of metformin and sitagliptin for 16 weeks (n = 681), and then, if glycemic control had not been achieved, were treated with a third add‐on oral antihyperglycemic drug for another 24 weeks (n = 291). The efficacy end‐point was change in glycated hemoglobin (HbA1c) in each stage, and the safety end‐point was adverse events with a focus on hypoglycemia. Results At week 16, the change in HbA1c was −0.81% from baseline, and the percentages of patients who achieved HbA1c targets of

Abstract Discovering the node roles in a network helps to solve diverse social problems. Role discovery attempts to predict the node roles from a network structure, and this method has been extensively studied in various fields. Role discovery using transfer learning has many advantages, but methods using this approach face two kinds of problems: domain-shift problems and model selection. To address these problems, we propose a general framework that includes network representation learning, domain adversarial learning for suppressing domain-shift problems, and model selection without using target labels. As a result of computational experiments, we show on publicly available datasets that the proposed model outperforms conventional methods, the proposed model selection method performs well without using target labels, and the proposed method can be used in real-world datasets. Furthermore, we found that our framework suppressed domain-shift problems, worked well even with differences between networks, and could handle imbalanced classes.

Abstract Human amyloids have been shown to interact with viruses and interfere with viral replication. Based on this observation, we employed a synthetic biology approach in which we engineered virus-specific amyloids against influenza A and Zika proteins. Each amyloid shares a homologous aggregation-prone fragment with a specific viral target protein. For influenza we demonstrate that a designer amyloid against PB2 accumulates in influenza A-infected tissue in vivo. Moreover, this amyloid acts specifically against influenza A and its common PB2 polymorphisms, but not influenza B, which lacks the homologous fragment. Our model amyloid demonstrates that the sequence specificity of amyloid interactions has the capacity to tune amyloid-virus interactions while allowing for the flexibility to maintain activity on evolutionary diverging variants.

Liver failure: A NEAT possibility for treatment A long noncoding RNA molecule, one that does not encode the synthesis of protein, is implicated in acute liver failure (AHF) and might offer a new target for drugs to treat the condition. AHF can be induced by various factors, including viruses, drugs, alcohol abuse, and inherited traits. Ke Cheng, Yujun Zhao and colleagues at Central South University in Changsha, China investigated the role of this RNA, called NEAT1, in cell and animal models of AHF. They identified increased production of NEAT1, which suppressed liver cell proliferation and promoted liver cell death. They also uncovered molecular details of the mechanisms underlying these effects, in which the RNA altered the production and regulatory modification of certain proteins. Further research should investigate the therapeutic possibilities of interfering with NEAT1 activity.

Background: The main objective of this study was to isolate fungi associated with Anthopleura xanthogrammica and measure their antimicrobial and enzymatic activities. A total of 93 fungal strains associated with A. xanthogrammica were isolated in this study, of which 32 isolates were identified using both morphological characteristics and internal transcribed spacer (ITS) sequence analysis. The antibacterial activities of 32 fungal isolates were tested against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Edwardsiella tarda, Vibrio harveyi, Fusarium oxysporum, and Pyricularia oryzae by agar diffusion assay. Extracellular hydrolytic enzyme activities of the fungal isolates were determined by agar diffusion assays. Enzyme activities were detected from clear halo size. Results: The isolated fungi belonged to 18 genera within 7 taxonomic orders of 1 phylum. The genera Aspergillaceae were the most diverse and common. The antimicrobial activities of 32 isolates were evaluated, and 19 (59.4%) of fungi isolate displayed unique antimicrobial activities. All fungal strains displayed at least one enzyme activity. The most common enzyme activities in the fungi isolates were amylase and protease, while the least common were pectinase and xylanase. Conclusions: This is first report on the sea anemone-derived fungi with antimicrobial and enzyme activities. Results indicated that sea anemone is a hot spot of fungal diversity and a rich resource of bioactive natural products. Keywords: Anthopleura xanthogrammica, Antimicrobial activity, Characterization of fungi, Diversity, Enzymatic activity, Internal transcribed spacer, Isolation of fungi, Marine fungi, Sea anemone

Enrichment of trace bioactive constituents and metabolites from complex biological samples is challenging. This study presented a one-pot synthesis of magnetic polydopamine nanoparticles (Fe3O4@SiO2@PDA NPs) with multiple recognition sites for the magnetic dispersive solid-phase extraction (MDSPE) of ginsenosides from rat plasma treated with white ginseng. The extracted ginsenosides were characterized by combining an ultra-high-performance liquid chromatography coupled to a high-resolution mass spectrometry with supplemental UNIFI libraries. Response surface methodology was statistically used to optimize the extraction procedure of the ginsenosides. The reusability of Fe3O4@SiO2@PDA NPs was also examined and the results showed that the recovery rate exceeded 80% after recycling 6 times. Furthermore, the proposed method showed greater enrichment efficiency and could rapidly determine and characterize 23 ginsenoside prototypes and metabolites from plasma. In comparison, conventional methanol method can only detect 8 ginsenosides from the same plasma samples. The proposed approach can provide methodological reference for the trace determination and characterization of different bioactive ingredients and metabolites of traditional Chinese medicines and food. Keywords: Fe3O4@SiO2@PDA NPs, Multiple recognition sites, Magnetic dispersive solid-phase extraction, Enrichment, Ginsenosides

For the surface-mount permanent magnet synchronous motors (SPMSM) with fractional slot concentrated windings, the winding distribution of per phase under different poles is uneven, which results in unbalanced magnetic pull (UMP) between the stator and rotor. UMP has an important impact on the performance and service life of the motor. In this paper, a new permanent magnet (PM) structure is proposed to reduce UMP and torque fluctuation of the fractional slot SPMSM. Furthermore, a 48p/54s SPMSM is taken as an example, the proposed PM structure is optimized by the Taguchi method which can comprehensively consider the control factors and noise factors. The effects of various variables and process error on UMP, torque fluctuation and robustness of results are analyzed respectively. Finally, the optimized PM structure is obtained, which improves the operation stationarity.

Maximum rank distance (MRD for short) codes lately attract more attention due to their various applications in storage systems, network coding, cryptography and space time coding. Similar to Reed-Solomon codes in classical coding theory, Gabidulin codes are the most prominent family of MRD codes. Due to their poor performance in list decoding or in constructing McEliece-type cryptosystems, the focus moves from Gabidulin codes to other non-Gabidulin codes. A natural following challenge is then to see if we can construct an infinite family of MRD codes that are not equivalent to Gabidulin codes. In this paper, we utilize Dickson matrices to construct an infinite family of Fq-linear MRD codes. Our codes are characterized by each of their codewords corresponding to a linearized polynomial with leading coefficient determined by one of any other coefficients. The family of codes corresponding to the set of linearized polynomials with leading coefficients dependent on the linear terms provides an extension to both Twisted Gabidulin codes and generalized Twisted Gabidulin codes for dimensions 1 and n-1. Lastly, we also provide some analysis on the equivalence between our proposed codes with some known families of MRD codes.

Feshbach resonances are transiently trapped states along a reaction coordinate, providing a probe to the reaction’s potential energy surface (PES) but difficult to analyze in polyatomic systems. Here the authors identify Feshbach resonances in a reacting 4-atom system by state-to-state quantum dynamics using a full-dimensional PES.

Nanoliposome is a useful dosage form to increase solubility and absorption of simvastatin (SMV), and consequently improves its therapeutic effects. However, in vivo toxicity of SMV could also be elevated accompanied by the absorption enhancement, which is a decisive factor for the clinical application of SMV nanoliposome (SMV-Lipo), but has not been studied systematically and reported so far. In this study, organ toxicity of SMV-Lipo was evaluated in mice in the presence and absence of isoproterenol and compared to those of free SMV. Results demonstrated that compared to free SMV, the SMV-Lipo administrated at an equal dose of 25 mg/kg/d led to severe myocardiotoxicity, hepatotoxicity at baseline and more pronounced liver injury with elevation of alanine aminotransferase. In addition, muscular adverse effect was also observed in SMV-Lipo treated group but not in SMV group. Pharmacokinetic studies revealed that compared to free SMV, the SMV-Lipo administration significantly improved the plasma SMV concentration, and the oral bioavailability was 6.5 times of free SMV. Notably, when the dosage of free SMV increased to 50 mg/kg/d, yielding the comparable plasma concentration as SMV-Lipo given at 25 mg/kg/d, the myocardiotoxicity was observed in free SMV treated mice as well, which further confirmed that the enhanced absorption of SMV by the nanoliposomal formulation resulted in more severe myocardiotoxicity than the equal dose of free SMV. Keywords: Simvastatin, Nanoliposome, Myocardiotoxicity, Muscular toxicity, Hepatotoxicity

Background: Exploring the pharmacokinetic (PK) changes of various active components of single herbs and their combinations is necessary to elucidate the compatibility mechanism. However, the lack of chemical standards and low concentrations of multiple active ingredients in the biological matrix restrict PK studies. Methods: A putative multiple reaction monitoring strategy based on liquid chromatography coupled with mass spectrometry (LC–MS) was developed to extend the PK scopes of quantification without resorting to the use of chemical standards. First, the compounds studied, including components with available reference standard (ARS) and components lacking reference standard (LRS), were preclassified to several groups according to their chemical structures. Herb decoctions were then subjected to ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis with appropriate collision energy (CE) in MS2 mode. Finally, multiple reaction monitoring transitions transformed from MS2 of ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were used for ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry to obtain the mass responses of LRS components. LRS components quantification was further performed by developing an assistive group-dependent semiquantitative method. Results: The developed method was exemplified by the comparative PK process of single herbs Radix Ginseng (RG), Radix Polygala (RP), and their combinations (RG–RP). Significant changes in PK parameters were observed before and after combination. Conclusion: Results indicated that Traditional Chinese Medicine combinations can produce synergistic effects and diminish possible toxic effects, thereby reflecting the advantages of compatibility. The proposed strategy can solve the quantitative problem of LRS and extend the scopes of PK studies. Keywords: Herb–herb interactions, Liquid chromatography coupled with mass spectrometry, Pharmacokinetics study, Radix Ginseng, Radix Polygala

In undertaking a functional study of ceramic Li tripods, a common archaeological artifact in Northeast China during the Bronze Age, this study provides a crucial insight into both the function of these ceramics, plant resource strategies and human diets during this period. The precise function of the Li tripod has to date been controversial due to a lack of direct contextual evidence. Hence, this paper presents analyses of 10 Li tripods from six sites in the Chifeng area of Northeast China, all of which can be dated from their excavation contexts to the Lower Xiajiadian cultural period (3,900–3,400 cal a B.P.). The interior and exterior surfaces of the tripods were analyzed using starch grain analysis, phytolith analysis and microfossil charcoal analysis. A total of 133 starch grains were recovered, of which 111 (83.46%) were found on 80% of the interior surfaces examined. Further analysis found that these starch grains had damage features specifically gelatinised characteristics, which were consistent with the starch grains that had been boiled in our cooking simulations. In addition, there were obvious soot traces on the surfaces of the tripods, 2,835 microfossil charcoal grains not completely burned were identified, and 70% of the exterior surface samples had a higher frequency of contact with fire. These findings serve to confirm that Li tripods were used in the cooking of food. Of the 133 starch grains found, only 62 could be identified to species level. These were foxtail millet (Setaria italica) and broomcorn millet (Panicum milliaceum) and plants from Triticeae taxa, as well as roots and tubers. The 3,424 phytoliths recovered from the 10 tripods were found to belong to the Panicoideae and Pooideae genera, of which the husks from foxtail and broomcorn millets from the Panicoideae genus accounted for 6.19% of the total. These results indicate that millets, the Triticeae, roots, and tubers, in addition to plants from Panicoideae and Pooideae genera, were utilized in the Chifeng area of Northeast China during the Bronze Age. This study deepens our understanding of the local subsistence patterns and the social context of early Bronze age civilization in the region.

To solve the instability problem of wind turbine power output, the wind power was predicted, and a wind power prediction algorithm optimized by the backpropagation neural network based on the CSO (cat swarm optimization) algorithm was studied, and a wind farm energy storage system model was built on this basis. By collecting the wind power plant’s historical wind speed, power, and other parameters, the short-term wind farm output power was predicted, and the operation of the wind farm energy storage system was controlled to suppress the output power of the wind farm when the wind farm was connected to the grid so as to improve the stability of the output power of the wind farm. At the same time, typical wind farm data were taken as an example to verify the feasibility of the proposed method.

BackgroundSevere hyperlipidemia is characterized by markedly elevated blood triglyceride levels and severe early-onset cardiovascular diseases, pancreatitis, pancreatic necrosis or persistent multiple organ failure if left untreated. It is a rare autosomal recessive metabolic disorder originated from the variants of lipoprotein lipase gene, and previous studies have demonstrated that most cases with severe hyperlipidemia are closely related to the variants of some key genes for lipolysis, such as LPL, APOC2, APOA5, LMF1, and GPIHBP1. Meanwhile, other unidentified causes also exist and are equally worthy of attention.MethodsThe 29-day-old infant was diagnosed with severe hyperlipidemia, registering a plasma triglyceride level as high as 25.46 mmol/L. Whole exome sequencing was conducted to explore the possible pathogenic gene variants for this patient.ResultsThe infant was put on a low-fat diet combined with pharmacological therapy, which was successful in restraining the level of serum triglyceride and total cholesterol to a low to medium range during the follow-ups. The patient was found to be a rare novel homozygous duplication variant-c.45_48dupGCGG (Pro17Alafs*22) in GPIHBP1 gene-leading to a frameshift which failed to form the canonical termination codon TGA. The mutant messenger RNA should presumably produce a peptide consisting of 16 amino acids at the N-terminus, with 21 novel amino acids on the heels of the wild-type protein.ConclusionsOur study expands on the spectrum of GPIHBP1 variants and contributes to a more comprehensive understanding of the genetic diagnosis, genetic counseling, and multimodality therapy of families with severe hyperlipidemia. Our experience gained in this study is also contributory to a deeper insight into severe hyperlipidemia and highlights the importance of molecular genetic tests.

Bietti crystalline dystrophy (BCD) is an autosomal recessive inherited retinal disease, resulting in blindness in most patients. The etiology and development mechanism of it remain unclear. Given the defects in previous mouse models of BCD, we generated a new Cyp4v3−/− mouse model, using CRISPR/Cas9 technology, for investigating the pathogenesis of BCD. We estimated the ocular phenotypes by fundus imaging, optical coherence tomography (OCT) and full-field scotopic electroretinography, and investigated the histological features by Hematoxylin and Eosin staining, Oil Red O staining and immunofluorescence. This model effectively exhibited age-related progression that mimicked the human ocular phenotypes. Moreover, gas chromatography-mass spectrometry and RNA-seq analysis indicated that the defect of Cyp4v3 led to the abnormal lipid metabolism, inflammation activation and oxidative stress of retina. Notably, inflammation activation and oxidative stress could also promote the progression of BCD in light-induced retinal degeneration. In conclusion, our data provided evidence that we established a novel and more effective Cyp4v3 knockout preclinical mouse model for BCD, which served as a useful tool for evaluating the effect of drugs and gene therapy in vivo.

Individual variations in concentrations of rituximab in different B cell non-Hodgkin’s lymphoma subtypes and their relevance to efficacy were still unclear. From 2016 to 2021, a prospective clinical trial was conducted, and 510 samples with 6 uncommon subtypes of B-cell lymphoma were enrolled to examine the pharmacokinetic behaviour of rituximab and its impact on clinical outcomes, including complete response (CR), progression-free survival (PFS) and overall survival (OS). Considerable variability was observed in the rituximab trough concentration in the first cycle (C1-trough, 1.16–55.52 μg/ml) in patients with different lymphoma subtypes. Patients with “double-hit” lymphoma (4.01 ± 0.77 μg/ml) or mantle cell lymphoma (MCL; 15.65 ± 16.45 μg/ml) had much lower C1-trough and worse outcomes. Great individual variation in the C1-trough existed among patients with mucosa-associated lymphoma (MALT), and the high C1-trough observed in patients treated with the RB regimen was associated with a better response than was obtained with R-CHOP (38.41 ± 14.13 μg/ml vs 15.49 ± 8.80 μg/ml, p = 0.0029). Despite the high aggressiveness of the cancer, Burkitt lymphoma patients receiving intensive chemotherapy had the highest C1-trough (28.85 ± 9.35 μg/ml) and maintained long-term PFS. The C1-trough in patients with mixed, unclassifiable B-cell lymphoma was close to 20 μg/ml, and these patients had acceptable outcomes. Overall, a low rituximab C1-trough was associated with adverse consequences, including persistent progression, early recurrence and a short OS, however, some high-risk factors appeared to be balanced by the presence of a high C1-trough. Basal levels of circulating CD19+ lymphocytes differed between and within patients with diverse lymphoma subtypes and were negatively correlated with C1-trough. Therefore, the traditional doses of rituximab are inadequate for patients with “double-hit” lymphoma and MCL. Increasing the initial rituximab dose according to the disease, high-risk factors and even the baseline CD19+ lymphocyte count will be new methods to optimize therapeutic regimens for patients with different lymphoma subtypes.