Effect of iTBS dual-target stimulation on lower limb function in patients with incomplete spinal cord injury:a randomized, single-blind,sham-controlled study.

OBJECTIVE: To explore the influence of intermittent theta burst stimulation (iTBS) dual-target stimulation on lower limb function in patients with incomplete spinal cord injury (iSCI). METHODS: A randomized, single -blind,sham-controlled trial was used in this study. Thirty iSCI patients with lower limb dysfunction meeting the inclusion criteria were randomly divided into a sham group and an iTBS group, with 15 cases in each group. The iTBS group received conventional rehabilitation therapy combined with iTBS dual-target stimulation on the central cerebral sulcus and the nerve root of the spinal cord injury segment. The sham group was treated with conventional rehabilitation therapy combined with iTBS dual-target sham stimulation therapy. Comprehensive functional assessment was performed on all patients before treatment, on the Day 3 and Day 21 of treatment.The main evaluation indicators were as follows: amplitude and latency of motor-evoked potential (MEP) in the anterior tibial muscles of both lower limbs,latency of sensory-evoked potential (SEP) of both lower limbs, knee flexor strength and knee extensor strength, lower extremity motor score (LEMS), lower extremity sensory score (LESS), spinal cord independence measure (SCIM) score and gait parameters (stride speed, stride frequency, stride length, ground reaction force). RESULTS: On day 21 of treatment, in the iTBS group, the MEP amplitude of the anterior tibial muscles increased, the latency of MEP shortened, knee flexor strength and knee extensor strength increased, and the lower extremity motor score and SCIM score of both lower limbs increased. In addition, there were statistically significant differences in the muscle strength of the knee flexion muscle, knee extensor muscle, MEP amplitude, LEMS and SCIM between the two groups (p<0.05). Among the 10 patients who could walk with an assisted walker, the step length and step frequency of the iTBS group were increased compared with the sham group after treatment (p<0.01), and the ground reaction force (GRF) was increased (p<0.05). There was no significant difference in the LESS of the lower limbs between the two groups (p > 0.05). CONCLUSIONS: ITBS dual-target stimulation can significantly improve the motor function of both lower limbs in patients with iSCI but does not significantly improve the sensory function of both lower limbs. Therefore, this treatment mode may participate in the reconstruction and repair of some nerve circuits in patients with iSCI. In addition, iTBS dual-target stimulation can improve the ability of iSCI patients to perform daily living.

Small bowel adenocarcinoma of the jejunum detected by double contrast enhanced ultrasound: a case report of a novel ultrasound modality.

Background: Small Bowel Adenocarcinoma (SBA) is rare, occult and life-threatening malignancy in digestive system. Given low incidence and nonspecific symptoms, SBA is frequently detected in later stages. Double contrast enhanced ultrasound (DCEUS) is an innovative imaging technique applied to visualize the gastrointestinal tract, merging intravenous contrast-enhanced ultrasound with oral contrast-enhanced ultrasound. In this case, DCEUS was utilized and successfully detected an SBA of the jejunum. Case presentation: A Chinese woman, aged 64, sought consultation in the gastroenterology department at our hospital, reporting symptoms of abdominal pain. Three months before entering the hospital, she underwent gastroscopy and colonoscopy which suggested chronic gastritis, and she was treated with oral drugs. However, her symptoms were not relieved, and even worsened. To further investigate, DCEUS was performed. The oral contrast agent dilated the luminal space of the upper gastrointestinal tract, resolving the hindrance caused by gas in the gastrointestinal tract and creating an acoustic window for scanning. Through this acoustic window, oral agent contrast-enhanced ultrasound (OA-CEUS) revealed a localized thickening of jejunal intestinal wall measuring 4x3 cm. Following intravenous injection of ultrasound contrast agent, the jejunal lesion exhibited faster enhancement and heterogeneous hyper-enhancement. Finally, the patient underwent jejunal tumor resection. Pathological examination revealed a jejunal adenocarcinoma. Conclusion: The timely diagnosis of SBA can be challenging. DCEUS may have the potential to contribute to diagnosis and detailed evaluation of SBA, particularly in cases involving jejunum. Further researches are needed to fully explore the benefits of DCEUS in the standard diagnostic approach for small bowel diseases.

The role of sex hormone binding globulin levels in the association of surgical and natural premature menopause with incident type 2 diabetes.

OBJECTIVE: To examine associations of surgical and natural menopause before the age of 40 years with the risk of type 2 diabetes (T2D) in women. METHODS: A total of 273,331 women from the United Kingdom were recruited between 2006 and 2010 in the UK Biobank (UKB) study, and 146,343 women aged 40 to 69 years who were postmenopausal at baseline were included in the analysis. Surgical menopause and natural premature menopause were defined as bilateral oophorectomy before the age of 40 and menopause before the age of 40 without oophorectomy, respectively. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between premature menopause and the incidence of T2D. RESULTS: During a median follow-up of 10.4 years, 47 women with surgical premature menopause, 244 women with natural premature menopause, and 4724 women without premature menopause developed T2D. Compared with women without premature menopause, both surgical premature menopause (adjusted HR = 1.46, 95 % CI: 1.09-1.95; P = 0.01) and natural premature menopause (adjusted HR = 1.20, 95 % CI: 1.06-1.37; P < 0.01) were associated with higher risks of incident T2D in the multivariable-adjusted models. Additionally, we observed a significant interaction between levels of sex hormone binding globulin (SHBG) (Pinteraction < 0.01) and the effects of premature menopause on incident T2D. The association between premature menopause and T2D risk appeared to be stronger in women with higher SHBG levels. Furthermore, a joint association was detected between premature menopause and the genetic risk score (GRS) of T2D, with a higher score indicating a higher risk of developingT2D. The highest risk of T2D was observed with higher T2D GRS and surgical premature menopause (adjusted HR = 2.61, 95 % CI: 1.65-4.12; P < 0.01). CONCLUSIONS: Surgical menopause and natural menopause before the age of 40 years were associated with an increased risk of T2D among postmenopausal women. The findings also suggest potential interactions of premature menopause with SHBG levels, with the association appearing to be stronger in higher SHBG levels, as well as a joint association between menopause status and genetic risk factors on T2D incidence.

The Fill-Mask Association Test (FMAT): Measuring propositions in natural language.

Recent advances in large language models are enabling the computational intelligent analysis of psychology in natural language. Here, the Fill-Mask Association Test (FMAT) is introduced as a novel and integrative method leveraging Masked Language Models to study and measure psychology from a propositional perspective at the societal level. The FMAT uses Bidirectional Encoder Representations from Transformers (BERT) models to compute semantic probabilities of option words filling in the masked blank of a designed query (i.e., a clozelike contextualized sentence). The current research presents 15 studies that establish the reliability and validity of the FMAT in predicting factual associations (Studies 1A-1C), measuring attitudes/biases (Studies 2A-2D), capturing social stereotypes (Studies 3A-3D), and retrospectively delineating lay perceptions of sociocultural changes over time (Studies 4A-4D). Empirically, the FMAT replicated seminal findings previously obtained with human participants (e.g., the Implicit Association Test) and other big-data text-analytic methods (e.g., word frequency analysis, the Word Embedding Association Test), demonstrating robustness across 12 BERT model variants and diverse training text corpora. Theoretically, the current findings substantiate the propositional (vs. associative) perspective on how semantic associations are represented in natural language. Methodologically, the FMAT allows for more fine-grained language-based psychological measurement, with an R package developed to streamline its workflow for use on broader research questions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer.

More than 1.9 million new colorectal cancer (CRC) cases and 935000 deaths were estimated to occur worldwide in 2020, representing about one in ten cancer cases and deaths. Overall, colorectal ranks third in incidence, but second in mortality. More than half of the patients are in advanced stages at diagnosis. Treatment options are complex because of the heterogeneity of the patient population, including different molecular subtypes. Treatments have included conventional fluorouracil-based chemotherapy, targeted therapy, immunotherapy, etc. In recent years, with the development of genetic testing technology, more and more targeted drugs have been applied to the treatment of CRC, which has further prolonged the survival of metastatic CRC patients.

Accuracy of dental implant placement using different dynamic navigation and robotic systems: an in vitro study.

Computer-aided implant surgery has undergone continuous development in recent years. In this study, active and passive systems of dynamic navigation were divided into active dynamic navigation system group and passive dynamic navigation system group (ADG and PDG), respectively. Active, passive and semi-active implant robots were divided into active robot group, passive robot group and semi-active robot group (ARG, PRG and SRG), respectively. Each group placed two implants (FDI tooth positions 31 and 36) in a model 12 times. The accuracy of 216 implants in 108 models were analysed. The coronal deviations of ADG, PDG, ARG, PRG and SRG were 0.85 ± 0.17 mm, 1.05 ± 0.42 mm, 0.29 ± 0.15 mm, 0.40 ± 0.16 mm and 0.33 ± 0.14 mm, respectively. The apical deviations of the five groups were 1.11 ± 0.23 mm, 1.07 ± 0.38 mm, 0.29 ± 0.15 mm, 0.50 ± 0.19 mm and 0.36 ± 0.16 mm, respectively. The axial deviations of the five groups were 1.78 ± 0.73°, 1.99 ± 1.20°, 0.61 ± 0.25°, 1.04 ± 0.37° and 0.42 ± 0.18°, respectively. The coronal, apical and axial deviations of ADG were higher than those of ARG, PRG and SRG (all P < 0.001). Similarly, the coronal, apical and axial deviations of PDG were higher than those of ARG, PRG, and SRG (all P < 0.001). Dynamic and robotic computer-aided implant surgery may show good implant accuracy in vitro. However, the accuracy and stability of implant robots are higher than those of dynamic navigation systems.

[Meteorological Influences on Annual Variation and Trend of Autumn Surface Ozone in the Pearl River Delta].

Based on the ozone （O3） monitoring data of the Pearl River Delta （PRD） from 2015 to 2022 and the reanalysis of meteorological data, the impact of meteorological conditions on the annual variation and trends of the maximum daily 8-hour average O3 concentration （MDA8-O3） were quantified using multiple linear regression （MLR） and LMG methods. The results indicated that the MLR model constructed using meteorological parameters from individual months in autumn better simulated the variation in MDA8-O3 compared to that in the model built using meteorological parameters from the entire autumn season. The combined influence of total cloud cover, relative humidity, 2 m maximum temperature, and 850 hPa zonal wind led to a reduction of 34.1 µg·m-3 in MAD8-O3 in 2020 compared to that in 2019, with contributions of 31.3%, 45.2%, 15.8%, and 6.7%, respectively. The observed trends of MDA8-O3 in the PRD for September, October, November, and the autumn season during 2015-2022 were 7.3, 5.2, 4.8, and 5.8 µg·ï¼ˆm3·a）-1, respectively. Among these, the trends driven by meteorological factors were 3.6, 2.4, 2.4, and 3.1 µg·ï¼ˆm3·a）-1. Overall, meteorological conditions contributed 53.4% to the variations in autumn MDA8-O3 in the PRD from 2015 to 2022.

Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy.

Despite the considerable advancements in chemotherapy as a cornerstone modality in cancer treatment, the prevalence of complications and pre-existing diseases is on the rise among cancer patients along with prolonged survival and aging population. The relationships between these disorders and cancer are intricate, bearing significant influence on the survival and quality of life of individuals with cancer and presenting challenges for the prognosis and outcomes of malignancies. Herein, we review the prevailing complications and comorbidities that often accompany chemotherapy and summarize the lessons to learn from inadequate research and management of this scenario, with an emphasis on possible strategies for reducing potential complications and alleviating comorbidities, as well as an overview of current preclinical cancer models and practical advice for establishing bio-faithful preclinical models in such complex context.

Analysis of the causal relationship between gut microbiota and bone remodeling growth factor from the gene association.

BACKGROUND: A growing body of evidence indicates a close association between the gut microbiota (GM) and the bone remodeling (BR) process, raising suspicions that the GM may actively participate in BR by modulating the levels of growth factors. However, the precise causal relationship between them remains unclear. Due to many confounding factors, many microorganisms related to BR growth factors have not been identified. We aimed to elucidate the causal relationship between the GM and BR growth factors. METHODS: We evaluated the genome-wide association study (GWAS) summary statistics for GM and five common growth factors associated with BR: namely, bone morphogenetic proteins (BMP), transforming growth factors(TGF), insulin growth factors (IGFs), epidermal growth factors (EGFs), and fibroblast growth factors (FGF). The causal relationship between the GM and BR growth factors was studied by double-sample Mendelian randomized analysis. We used five Mendelian randomization (MR) methods, including inverse variance-weighted (IVW), MR-Egger, simple mode, weighted median, and weighted model methods. RESULTS: Through MR analysis, a total of 56 bacterial genera were co-identified as associated with BMP, TGF, IGF, EGF, and FGF. Among them, eight genera were found to have a causal relationship with multiple growth factors: Marvinbryantia was causally associated with BMP-6 (P = 0.018, OR = 1.355) and TGF-ß2 (P = 0.002, OR = 1.475); Lachnoclostridium, BMP-7 (P = 0.021, OR = 0.73) and IGF-1 (P = 0.046, OR = 0.804); Terrisporobacter, TGF-ß (P = 0.02, OR = 1.726) and FGF-23 levels (P = 0.016, OR = 1.76); Ruminiclostridium5, TGF-ß levels (P = 0.024, OR = 0.525) and FGFR-2 (P = 0.003, OR = 0.681); Erysipelatoclostridium, TGF-ß2 (P = 0.001, OR = 0.739) and EGF and its receptor (EGFR) (P = 0.012, OR = 0.795); Eubacterium_brachy_group, FGFR-2 (P = 0.045, OR = 1.153) and EGF (P = 0.013, OR = 0.7); Prevotella9 with EGFR (P = 0.022, OR = 0.818) and FGFR-2 (P = 0.011, OR = 1.233) and Faecalibacterium with FGF-23 (P = 0.02, OR = 2.053) and IGF-1 (P = 0.005, OR = 0.843). CONCLUSION: We confirmed the causal relationship between the GM and growth factors related to BR, which provides a new perspective for the study of BR, through targeted regulation of specific bacteria to prevent and treat diseases and growth factor-mediated BR disorders.

Application progress of exergames in health interventions for the elderly. / 运动游戏在老年人健康干预中的应用进展.

With the aging population in China, health issues among the elderly are becoming increasingly prominent, leading to a rapidly growing demand for health interventions for the elderly. Exergames are one of the important emerging methods in the field of health interventions for the elderly, widely used and yielding positive results. While research on exergames is well-established abroad, it is still in its infancy in China, lacking reports on the types, interaction forms, intervention content, application status, and effectiveness of exergames. Exergames are suitable for widespread use among the elderly in China, and there is a need to accelerate the development and application of exergames in the field of health interventions for the elderly in China.

Maternal mRNA deadenylation is defective in in vitro matured mouse and human oocytes.

Oocyte in vitro maturation is a technique in assisted reproductive technology. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (MII) oocytes compared to those matured in vivo in bovines, mice, and humans. The mechanisms underlying this phenomenon are poorly understood. Here, we use poly(A) inclusive RNA isoform sequencing (PAIso-seq) for profiling the transcriptome-wide poly(A) tails in both in vivo and in vitro matured mouse and human oocytes. Our results demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes. Moreover, the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes, contributing to reduced translation of these deadenylase machinery components and subsequently impaired global maternal mRNA deadenylation. Our findings highlight impaired maternal mRNA deadenylation as a distinct molecular defect in in vitro MII oocytes.

Versatile Curve Design by Level Set with Quadratic Convergence.

Many 3D mesh processing tasks revolve around generating and manipulating curves on surface meshes. While it is intuitive to explicitly model these curves using mesh edges or parametric curves in the ambient space, these methods often suffer from numerical instability or inaccuracy due to the projection operation. Another natural strategy is to adapt spline based tools, these methods are quite fast but are hard to be extended to more versatile constraints and need heavy manual interactions. In this paper, we present an efficient and versatile approach to curve design based on an implicit representation known as the level set. While previous works have explored the use of the level set to generate curves with minimal length, they typically have limitations in accommodating additional conditions for rich and robust control. To address these challenges, we formulate curve editing with constraints like smoothness, interpolation, tangent control, etc., via a level set based variational problem by constraining the values or derivatives of the level set function. However, the widely used gradient flow strategy converges very slowly for this complicated variational problem compared to the classical geodesic one. Thus, we propose to solve it via Newton's method enhanced by local Hessian correction and a trust-region strategy. As a result, our method not only enables versatile control, but also excels in terms of performance due to nearly quadratic convergence and almost linear complexity in each iteration via narrow band acceleration. In practice, these advantages effectively benefit various applications, such as interactive curve manipulation, boundary smoothing for surface segmentation and path planning with obstacles as demonstrated.

Physiological and Cellular Ultrastructural Responses of Isatis indigotica Fort. under Salt Stress.

This study aimed to analyze the effects of salt stress on the growth physiology and plant-cell ultrastructure of Isatis indigotica Fort. (I. indigotica) to evaluate its adaptability under salt stress. The effects of different concentrations of salt (NaCl; 0, 25, and 300 mmol·L-1) on the agronomic traits, activities of related enzymes, ion balance, and mesophyll-cell ultrastructure of I. indigotica were studied in a controlled pot experiment. Results showed that compared with those of the control group, the aerial-part fresh weight, underground fresh weight, tiller number, root length, root diameter, plant height, and leaf area of salt-stressed I. indigotica increased at 25 mmol·L-1 and then decreased at 300 mmol·L-1. The changes in levels of superoxide dismutase, peroxidase, ascorbate peroxidase, and catalase showed a similar trend, with significant differences compared with control group. Salt stress altered the ion balance of I. indigotica, resulting in a significant increase in Na+ content and a significant decrease in K+ content. The contents of Ca2+ and Mg2+ changed to varying degrees. The analysis of the microstructure of the root showed that under salt treatment, the epidermal cells of the root significantly thickened and the diameter of the xylem decreased. The results of ultrastructural analysis of mesophylls showed that salt stress can cause cell-membrane contraction, cell-gap enlargement, disorder in the structures of chloroplasts and mitochondria, and an increase in the number of osmiophilic particles. These changes were aggravated by the increase in NaCl concentration. This study reveals the response of I. indigotica to salt stress and provides a basis for further study on the salt-tolerance mechanism of I. indigotica.

The Dependence of Solid Electrolyte Interphase on the Crystal Facet of Current Collector in Li Metal Battery.

The continuous electrolyte decomposition and uncontrolled dendrite growth caused by the unstable solid electrolyte interphase (SEI) have largely hindered the development of Li metal batteries. Here, we demonstrate that tuning the facet of current collector can regulate the composition of SEI and the subsequent Li deposition behavior using single-crystal Cu foils as an ideal platform. The theoretical and experimental studies reveal that the (100) facet of Cu possesses strong adsorption to anions, guiding more anions to participate preferentially in the inner Helmholtz plane and further promoting the formation of the stable inorganic-rich SEI. Consequently, the single-crystal Cu foils with a single [100] orientation (s-Cu(100)) achieve the dendrite-free Li deposition with enhanced Li plating/stripping reversibility. Moreover, the Li anode deposited on s-Cu(100) can stabilize the operation of an Ah-level pouch cell (350 Wh kg-1) with a low negative/positive capacity ratio (~2) and lean electrolyte (2.4 g Ah-1) for 150 cycles. Impressively, this strategy demonstrates universality in a series of electrolytes employed different anions. This work provides new insights into the correlation between the SEI and current collector, opening a universal avenue towards high-performance Li metal batteries.

Accurately recognizing chromium species with multi-functionalized nano Au-based sensor array.

High-resolution identification of chromium (Cr) species, especially various organic-Cr complexes, in a convenient and economically-feasible manner is the prerequisite for achieving the advanced treatment of chromium wastewater. To this end, a colorimetric nano-Au sensor array was developed by taking advantage of the UV-spectra shift of gold nanoparticles (Au NPs) upon interaction with Cr species; specifically, four molecular modifiers [i.e., iminodiacetic acid (IDA), tripolyphosphate (TPP), cetyltrimethylammonium bromide (CTAB), and 1,5-diphenylcarbazide (DPC)] were intentionally employed for assembling nano-Au array receptors, which showed respective responses toward different Cr species through the formation of coordination, hydrophobic interaction, electrostatic attraction, and redox reaction, respectively; the "fingerprint" differences of the unique optical properties were then integrated for semi-quantitatively recognizing Cr species by pattern recognition techniques. Eleven ubiquitous Cr species [i.e., Cr(III), Cr(VI), and various Cr(III)-organic complexes] served as the model samples, which could be sensitively identified, no matter in individual or mixture mode, by the developed nano-Au sensor array on the basis of the colorimetric responses resulted from diverse nano-Au-aggregation behaviors, with excellent anti-interference ability in the simulated or actual water scenario. Attractively, the nano-Au sensor array can achieve very sensitive detection limit of the quantitative analyses of Cr species in a prompt in-situ manner, which usually requires a two-step process of separation and detection for the conventional analytical methods. Such a convenient strategy of Cr species discrimination conduces to rationally designing specific protocols for the advanced treatment of chromium wastewater.

Nonlinear optical signatures of topological Dirac fermion.

Dirac fermion in topological materials exhibits intriguing nonlinear optical responses. However, their direct correlation with the linearly dispersed band remains elusive experimentally. Here, we take topological semimetal ZrSiS as a paradigm, unveiling three unique nonlinear optical signatures of Dirac fermion. These signatures include strong quadrupolar response, quantum interference effect, and exponential divergent four-wave mixing (FWM), all of which are described by the prominent third-order nonlinear optical susceptibility. Resonantly enhanced by linear bands, quadrupolar second harmonic generation in centrosymmetric bulk overwhelms the electric-dipole contribution at the surface with inherent inversion symmetry breaking. Furthermore, owing to the interference between multiple resonant transition pathways within linear bands, difference-frequency FWM is several orders of magnitude stronger than sum-frequency FWM and third harmonic generation. The difference-frequency FWM further displays an inverse-square divergence toward degenerate excitation, whose scaling law perfectly matches with the long-sought behavior of Dirac fermion. These signatures lay the solid foundation toward the practical applications of topological materials in nonlinear optoelectronics and photonics.

Microvesicles-delivering Smad7 have advantages over microvesicles in suppressing fibroblast differentiation in a model of Peyronie's disease.

BACKGROUND: This study compared the differences of microvesicles (MVs) and microvesicles-delivering Smad7 (Smad7-MVs) on macrophage M1 polarization and fibroblast differentiation in a model of Peyronie's disease (PD). METHODS: Overexpression of Smad7 in rat BMSCs was obtained by pCMV5-Smad7 transfection. MVs were collected from rat BMSCs using ultracentrifugation. In cells, 100 µg/mL of MVs or Smad7-MVs were used to treat the 100 ng/mL of lipopolysaccharide (LPS)-induced RAW264.7 cells or 10 ng/mL of recombinant transforming growth factor-ß1 (TGF-ß1)-induced fibroblasts. The pro-inflammatory cytokines and markers of M1 macrophages were measured in RAW264.7 cells, and the migration and markers of fibroblast differentiation were measured in fibroblasts. In rats, 50 µg of MVs or Smad7-MVs were used to treat the TGF-ß1-induced animals. The pathology of tunica albuginea (TA), the markers of M1 macrophages and fibroblast differentiation in the TA were measured. RESULTS: The MVs or Smad7-MVs treatment suppressed the LPS-induced macrophage M1 polarization and TGF-ß1-induced fibroblast differentiation. Moreover, the Smad7-MVs treatment decreased the fibroblast differentiation compared with the MVs treatment. In the TGF-ß1-induced TA of rats, MVs or Smad7-MVs treatment ameliorated the TA fibrosis by suppressing the macrophage M1 polarization and fibroblast differentiation. There was no significance on the M1-polarized macrophages between the MVs treatment and the Smad7-MVs treatment. Meanwhile, the Smad7-MVs treatment had an edge in terms of suppressing the fibroblast differentiation in the TGF-ß1-induced PD model compared with the MVs treatment. CONCLUSIONS: This study demonstrated that Smad7-MVs treatment had advantages over MVs treatment in suppressing of fibroblast differentiation in a model of PD.

Low NDRG2, regulated by the MYC/MIZ-1 complex and methylation, predicts poor outcomes in DLBCL patients.

Diffuse large B-cell lymphoma (DLBCL) represents the most common tumor in non-Hodgkin's lymphoma. N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor highly expressed in healthy tissues but downregulated in many cancers. Although cell proliferation-related metabolism rewiring has been well characterized, less is known about the mechanism of metabolic changes with DLBCL. Herein, we investigated the expressions of NDRG2, MYC and Myc-interacting zinc finger protein 1 (MIZ-1) in seven human lymphoma (mostly DLBCLs) cell lines. NDRG2 expression was inversely correlated with the expressions of MYC and MIZ-1. Further, we explored the regulatory mechanism and biological functions underlying the lymphomagenesis involving NDRG2, MYC and MIZ-1. MYC and MIZ-1 promoted DLBCL cell proliferation, while NDRG2 induced apoptosis in LY8 cells. Moreover, NDRG2 methylation was reversed by the 5-Aza-2'-deoxycytidine (5-Aza-CDR) treatment, triggering the downregulation of MYC and inhibiting DLBCL cell survival. MYC interacts with NDRG2 to regulate energy metabolism associated with mTOR. Remarkably, supporting the biological significance, the converse correlation between NDRG2 and MYC was observed in human DLBCL tumor tissues (R = -0.557). Bioinformatics analysis further validated the association among NDRG2, MYC, MIZ-1, mTOR, and related metabolism genes. Additionally, NDRG2 (P = 0.001) and MYC (P < 0.001) were identified as promising prognostic biomarkers in DLBCL patients through survival analysis. Together, our data demonstrate that the MYC/MIZ-1 complex interplays with NDRG2 to influence the proliferation and apoptosis of DLBCL cells and show the characterizations of NDRG2, MYC and MIZ-1 for metabolism features and prediction prognosis in DLBCL.

Positive roles of the Ca2+ sensors GbCML45 and GbCML50 in improving cotton Verticillium wilt resistance.

As a universal second messenger, cytosolic calcium (Ca2+) functions in multifaceted intracellular processes, including growth, development and responses to biotic/abiotic stresses in plant. The plant-specific Ca2+ sensors, calmodulin and calmodulin-like (CML) proteins, function as members of the second-messenger system to transfer Ca2+ signal into downstream responses. However, the functions of CMLs in the responses of cotton (Gossypium spp.) after Verticillium dahliae infection, which causes the serious vascular disease Verticillium wilt, remain elusive. Here, we discovered that the expression level of GbCML45 was promoted after V. dahliae infection in roots of cotton, suggesting its potential role in Verticillium wilt resistance. We found that knockdown of GbCML45 in cotton plants decreased resistance while overexpression of GbCML45 in Arabidopsis thaliana plants enhanced resistance to V. dahliae infection. Furthermore, there was physiological interaction between GbCML45 and its close homologue GbCML50 by using yeast two-hybrid and bimolecular fluorescence assays, and both proteins enhanced cotton resistance to V. dahliae infection in a Ca2+-dependent way in a knockdown study. Detailed investigations indicated that several defence-related pathways, including salicylic acid, ethylene, reactive oxygen species and nitric oxide signalling pathways, as well as accumulations of lignin and callose, are responsible for GbCML45- and GbCML50-modulated V. dahliae resistance in cotton. These results collectively indicated that GbCML45 and GbCML50 act as positive regulators to improve cotton Verticillium wilt resistance, providing potential targets for exploitation of improved Verticillium wilt-tolerant cotton cultivars by genetic engineering and molecular breeding.