Venetoclax combined with azacitidine in blastic plasmacytoid dendritic cell neoplasm: a case report and comprehensive review on the current and future treatment.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare hematological malignancy with a highly aggressive behavior and median survival of <2 years. Especially, most BPDCN patients present with extensive and non-specific skin lesions, usually leading to misdiagnosis as a skin disease and delay therapy. As for treatment, most patients with BPDCN experience relapse shortly after treatment with the traditional regimens. The alleviation of skin symptoms reflects the effects of clinical treatments. Herein, we report a case of a 71-year-old man with intermittent and gradually expanding skin lesions over his chest, abdomen, and back for 1 year. On admission, physical examination revealed extensive skin lesions and multiple enlarged lymph nodes. Laboratory examinations showed pancytopenia and numerous malignant cells in the peripheral blood smear (60%), bone marrow aspirate smear (73.5%). Immunophenotyping using flow cytometry and immunohistochemistry presented large numbers of BPDCN cells in the bone marrow, cervical lymph nodes and dermal tissue. PET/CT revealed multiple enlarged lymph nodes and splenomegaly. Once the diagnosis was identified as BPDCN, the patient began treatment with the oral BCL2 inhibitor venetoclax and subcutaneously administered azacitidine. After the first course, skin lesions reduced markedly and complete remission was achieved in the bone marrow. Our study and current cumulative data according to reviewing systematically suggest that venetoclax combined with azacitidine is safe, effective, and applicable in the treatment of BPDCN, especially for elderly relapsed/refractory patients. This study, therefore, significantly contributes to the literature on the current and future treatment for BPDCN.

Association between plant microbiota and cadmium uptake under the influence of microplastics with different particle sizes.

Plant microbiota are an important factor impacting plant cadmium (Cd) uptake. However, little is known about how plant microbiota affects the Cd uptake by plants under the influence of microplastics (MPs) with different particle sizes. In this study, bacterial structure and assembly in the rhizosphere and endosphere in pakchoi were analyzed by amplicon sequencing of 16S rRNA genes under the influence of different particle sizes of polystyrene microplastics (PS-MPs) combined with Cd treatments. Results showed that there were no significant differences observed in the shoot endophytes among different treatments. However, compared to Cd treatment, larger-sized PS-MPs (2 and 20 µm) significantly increased community diversity and altered the structural composition of rhizosphere bacteria and root endophytes, while smaller-sized PS-MPs (0.2 µm) did not. Under the treatment of larger-sized PS-MPs, the niche breadth of rhizosphere bacteria and root endophytes were significantly increased. And larger-sized PS-MPs also maintained stability and complexity of bacterial co-occurrence networks, while smaller-sized PS-MPs reduced them. Furthermore, compared to Cd treatment, the addition of larger particle size PS-MPs decreased the proportion of homogeneous section, while increased the proportion of drift in root endophytic bacterial community assembly. The role of larger-sized MPs in the community assembly of rhizosphere bacteria was opposite. Using random forest and structural equation models, the study found that larger-sized PS-MPs can promote the colonization of specific bacterial taxa, such as Brevundimonas, AKAU4049, SWB02, Ellin6055, Porphyrobacter, Sphingorhabdus, Rhodobacter, Erythrobacter, Devosia and some other bacteria belonging to Alphaproteobacteria, in the rhizosphere and root endosphere. The colonization of these taxa can may induce the formation of biofilms in the roots, immobilize heavy metals through oxidation processes, and promote plant growth, thereby reducing Cd uptake by pakchoi. The findings of this study provide important insights into the microbial mechanisms underlying the influence of MPs with different particle sizes on plant Cd uptake.

Novel and recurrent hemizygous variants in BCORL1 cause oligoasthenoteratozoospermia by interfering transcription.

BACKGROUND: Oligoasthenoteratozoospermia (OAT) is a common cause of male infertility, of which the causes remain largely unknown. Recently, BCORL1 was identified as a contributor to male infertility from non-obstructive azoospermia (NOA) to OAT. OBJECTIVES: To identify novel and hotspot variants in BCORL1 from infertile men with OAT and reveal their outcomes of assisted reproductive treatments (ARTs). MATERIALS AND METHODS: Forty-six infertile men characterized by OAT were recruited from 2017 to 2022. Variants in OAT patients were identified by whole-exome sequencing (WES) and verified by Sanger sequencing. Papanicolaou staining was used for sperm morphology analysis. Pathogenicity of BCORL1 variants were analyzed by bioinformatics analysis, and further confirmed in vitro by using recombinant plasmids and cells. Meanwhile, ARTs were performed on these patients to investigate the appropriate clinical treatment strategy. RESULTS: We identified a novel hemizygous missense variant (NM_021946: c.G4171A; p.G1391R) and a recurrent variant (NM_021946: c.T2615G; p.V872G) in BCORL1 from four OAT patients. Notably, routine semen assessment and Papanicolaou staining revealed a special OAT phenotype of patients with BCORL1 variants, whose rare mature sperm characterized by acephalic and abnormal acrosome. Pathogenicity analysis showed the interaction between BCORL1 with histone deacetylases (HDACs) were disrupted after variance, accompanied with epigenetic alterations and finally the orderly transcriptions of spermatogenetic genes were interfering. Besides, clinical record presented the poor outcomes of ARTs in these patients with BCORL1 variants. DISCUSSION AND CONCLUSIONS: Our findings further expand the variant spectrum of BCORL1 related to OAT, and provide new evidences that BCORL1 acts as an important transcriptional regulator, participating in epigenetic regulation and directing the expression of key genes throughout spermatogenesis. The outcomes of ARTs will facilitate the genetic counseling and clinical treatment of infertile men with BCORL1 variants in the future.

Gastrodin Improves the Activity of the Ubiquitin-Proteasome System and the Autophagy-Lysosome Pathway to Degrade Mutant Huntingtin.

Gastrodin (GAS) is the main chemical component of the traditional Chinese herb Gastrodia elata (called "Tianma" in Chinese), which has been used to treat neurological conditions, including headaches, epilepsy, stroke, and memory loss. To our knowledge, it is unclear whether GAS has a therapeutic effect on Huntington's disease (HD). In the present study, we evaluated the effect of GAS on the degradation of mutant huntingtin protein (mHtt) by using PC12 cells transfected with N-terminal mHtt Q74. We found that 0.1-100 µM GAS had no effect on the survival rate of Q23 and Q74 PC12 cells after 24-48 h of incubation. The ubiquitin-proteasome system (UPS) is the main system that clears misfolded proteins in eukaryotic cells. Mutated Htt significantly upregulated total ubiquitinated protein (Ub) expression, decreased chymotrypsin-like, trypsin-like and caspase-like peptidase activity, and reduced the colocalization of the 20S proteasome with mHtt. GAS (25 µM) attenuated all of the abovementioned pathological changes, and the regulatory effect of GAS on mHtt was found to be abolished by MG132, a proteasome inhibitor. The autophagy-lysosome pathway (ALP) is another system for misfolded protein degradation. Although GAS downregulated the expression of autophagy markers (LC3II and P62), it increased the colocalization of LC3II with lysosomal associated membrane protein 1 (LAMP1), which indicates that ALP was activated. Moreover, GAS prevented mHtt-induced neuronal damage in PC12 cells. GAS has a selective effect on mHtt in Q74 PC12 cells and has no effect on Q23 and proteins encoded by other genes containing long CAGs, such as Rbm33 (10 CAG repeats) and Hcn1 (>30 CAG repeats). Furthermore, oral administration of 100 mg/kg GAS increased grip strength and attenuated mHtt aggregates in B6-hHTT130-N transgenic mice. This is a high dose (100 mg/kg GAS) when compared with experiments on HD mice with other small molecules. We will design more doses to evaluate the dose-response relationship of the inhibition effect of GAS on mHtt in our next study. In summary, GAS can promote the degradation of mHtt by activating the UPS and ALP, making it a potential therapeutic agent for HD.

Intraoperative application of low-dose dexmedetomidine or lidocaine for postoperative analgesia in pediatric patients following craniotomy: a randomized double-blind placebo-controlled trial.

Background: Postoperative pain is a common occurrence in pediatric patients following craniotomy, often leading to negative outcomes. Intravenous dexmedetomidine and lidocaine are commonly used adjuvant medicines in general anesthesia to reduce perioperative opioid consumption and relieve postoperative pain in adults. While they show promise for use in pediatrics, the evidence of their application in pediatric craniotomy patients is limited. Therefore, we aimed to compare the effects of dexmedetomidine and lidocaine on postoperative pain in pediatric patients following craniotomy. Methods: We conducted a randomized, double-blind, single-center trial on children scheduled for craniotomy. The 255 recruited participants aged 1-12 years were randomly assigned to intraoperatively receive a loading intravenous dose of either dexmedetomidine 1 µg·kg-1 or lidocaine 2 mg·kg-1 or normal saline for 15 min followed by dexmedetomidine 0.5 µg·kg-1·h-1 or lidocaine 1 mg·kg-1·h-1 or normal saline until the sutures of endocranium were completed. The primary outcome was the cumulative sufentanil consumption within 24 h post-surgery. Results: A total of 241 patients were included in the statistical analysis. The primary outcome did not show any significant differences among the three groups (median (IQR) lidocaine group: 3.36 (1.32-5.64) µg vs. dexmedetomidine group: 3.12 (1.36-6.39) µg vs. control group 3.46 (1.77-7.62) µg, p = 0.485). Among the secondary outcomes, there was a statistically significant but small reduction in sufentanil consumption within 2 h, postoperative FLACC/WBFS/NRS pain scores within 4 h after surgery and postoperative Ramsay sedation scores in dexmedetomidine group (p < 0.05). Regarding postoperative complications, the incidence of electrolyte disturbance within 24 and 48 h after surgery was significantly higher in control group compared to the other two groups. There were no significant differences in intraoperative opioid consumption, postoperative frequency of remedy medication, or length of hospitalization among the three groups. No adverse events related to lidocaine or dexmedetomidine were observed. Conclusions: There were no significant differences in the primary outcome among the three groups. Although dexmedetomidine showed some benefits in reducing postoperative opioid consumption within the first 2 h and pain intensity within the first 4 h post-surgery, these findings should be interpreted with caution. Further research is required to comprehensively assess the outcomes and determine the optimal administration strategy. Clinical Trial Registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR1800019411].

Enhanced immobilization of cadmium and lead in contaminated soil using calcium alginate-modified HAP biochar: Improvements in soil health and microbial diversity.

A novel adsorbent, calcium alginate-modified HAP (Hydroxyapatite)-wood ear mushroom sticks biochar (CA-HAPMB), was synthesized to enhance the immobilization of Cd and Pb in soil. Over 150 days, applying CA-HAPMB at concentrations of 0%-3% in contaminated soils from Chenzhou City in Hunan Province (CZ) and Shenyang City in Liaoning Province (SY) resulted in decreased effective concentrations of Cd and Pb. Specifically, in CZ soil, Cd and Pb decreased by 30.9%-69.3% and 31.9%-78.6%, respectively, while in SY soil, they decreased by 27.5%-53.7% and 26.4%-62.3%, respectively. Characterization results, obtained after separating CA-HAPMB from the soil, indicate that complexation, co-precipitation, and ion exchange play crucial roles in the efficient immobilization of Cd and Pb by CA-HAPMB. Additionally, adjusting the amount of CA-HAPMB added allows modulation of soil pH, leading to increased soil organic matter and nutrient content. Following treatment with CA-HAPMB for immobilizing Cd and Pb, soil bacteria abundance and diversity increased, further promoting heavy-metal immobilization.

Drying kinetics and energy efficiency of soot ash of smelting silicon manganese alloys under microwave heating.

When smelting silicon manganese alloy in an industrial electric furnace, it will produce smoke and dust waste gas, which can be utilized again back to the furnace and improve the utilization rate of raw materials after a particular trapping device and collection treatment. However, at higher moisture levels, they are prone to explode. Effects of various initial masses, initial moisture contents, and microwave output powers on the soot ash of smelting silicon manganese alloy were studies. The findings indicate that the microwave drying rate increases with all three variables. The time for complete microwave drying is directly proportional to the sample's initial moisture content and the sample's initial mass, and the time for complete microwave drying is inversely proportional to the microwave output power. The results demonstrate that the Modified Page model can accurately describe the microwave drying process. The experimental data were fitted experimentally by drying kinetic models. Microscopic characterization of soot ash from refining silico­manganese alloys before and after drying was carried out using FTIR and SEM. Through FTIR characterization, the peak value of the -OH absorption peak decreases upon drying, and SEM results in no agglomeration caused by microwave drying and better dispersion of the soot ash of the dried smelted silica­manganese alloys, all of which proved that microwaves could effectively remove water. It was discovered that the diffusion coefficient increased gradually with increasing power when it was computed using Fick's second law. The diffusion coefficient increases and then decreases as the moisture content increases. The diffusion coefficient decreases as the initial mass increases. Activation energy of microwave drying of soot ash from the refining of silicomanganese alloys was calculated to be -1.4467 W/g. Its purpose is to offer a detailed guide for the industrial drying of soot ash from silicomanganese alloy refinement using microwave drying technology.

Exploration the interaction of cadmium and copper toxic effects in pakchoi (Brassica chinensis L) roots through combinatorial transcriptomic and weighted gene co-expression network analysis.

The interaction between cadmium(Cd) and copper(Cu) during combined pollution can lead to more complex toxic effects on humans and plants.However, there is still a lack of sufficient understanding regarding the types of interactions at the plant molecular level and the response strategies of plants to combined pollution. To assess this, we investigated the phenotypic and transcriptomic patterns of pakchoi (Brassica chinensis L) roots in response to individual and combined pollution of Cd and Cu. The results showed that compared to single addition, the translocation factor of heavy metals in roots significantly decreased (p < 0.05) under the combined addition, resulting in higher accumulation of Cd and Cu in the roots. Transcriptomic analysis of pakchoi roots revealed that compared to single pollution, there were 312 and 1926 differentially expressed genes (DEGs) specifically regulated in the Cd2Cu20 and Cd2Cu100 combined treatments, respectively. By comparing the expression of these DEGs among different treatments, we found that the combined pollution of Cd and Cu mainly affected the transcriptome of the roots in an antagonistic manner. Enrichment analysis indicated that pakchoi roots upregulated the expression of genes involved in glucosetransferase activity, phospholipid homeostasis, proton transport, and the biosynthesis of phenylpropanoids and flavonoids to resist Cd and Cu combined pollution. Using weighted gene co-expression network analysis (WGCNA), we identified hub genes related to the accumulation of Cd and Cu in the roots, which mainly belonged to the LBD, thaumatin-like protein, ERF, MYB, WRKY, and TCP transcription factor families. This may reflect a transcription factor-driven trade-off strategy between heavy metal accumulation and growth in pakchoi roots. Additionally, compared to single metal pollution, the expression of genes related to Nramp, cation/H+ antiporters, and some belonging to the ABC transporter family in the pakchoi roots was significantly upregulated under combined pollution. This could lead to increased accumulation of Cd and Cu in the roots. These findings provide new insights into the interactions and toxic mechanisms of multiple metal combined pollution at the molecular level in plants.

FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer.

Programmed cell death 1 ligand 1 (PDL1)/programmed cell death 1 (PD1) blockade immunotherapy provides a prospective strategy for the treatment of colorectal cancer (CRC), but various constraints on the effectiveness of the treatment are still remaining. As reported in previous studies, follistatin-like 3 (FSTL3) could mediate inflammatory response in macrophages by induction lipid accumulation. Herein, we revealed that FSTL3 were overexpressed in malignant cells in the CRC microenvironment, notably, the expression level of FSTL3 was related to tumor immune evasion and the clinical efficacy of anti-PD1 therapy. Further studies determined that hypoxic tumor microenvironment induced the FSTL3 expression via HIF1α in CRC cells, FSTL3 could bind to the transcription factor c-Myc (354-406 amino acids) to suppress the latter's ubiquitination and increase its stability, thereby to up-regulated the expression of PDL1 and indoleamine 2,3-dioxygenase 1 (IDO1). The results in the immunocompetent tumor models verified that FSLT3 knockout in tumor cells increased the proportion of CD8+ T cells in the tumor microenvironment, reduced the proportion of regulatory T cells (CD25+ Foxp3+) and exhausted T cells (PD1+ CD8+), and synergistically improved the anti-PD1 therapy efficacy. To sum up, FSTL3 enhanced c-Myc-mediated transcriptional regulation to promote immune evasion and attenuates response to anti-PD1 therapy in CRC, suggesting the potential of FSTL3 as a biomarker of immunotherapeutic efficacy as well as a novel immunotherapeutic target in CRC.

Single and mixture toxicity of cadmium and copper to swim bladder in early life stages of Japanese medaka (Oryzias latipes).

Toxicity observed in aquatic ecosystems often cannot be explained by the action of a single pollutant. Likewise, evaluation standards formulated by a single effect cannot truly reflect the environmental quality requirements. The study of mixtures is needed to provide environmental relevance and knowledge of combined toxicity. In this study, the embryos of Japanese medaka (Oryzias latipes) were treated with individual and binary mixture of copper (Cu) and cadmium (Cd) until 12 days post-fertilization (dpf). Hatching, mortality, development, histology and gene expression were assessed. Our results showed that the highest concentration mixture of Cd (10 mg/L) and Cu (1 mg/L) affected survival, hatching time and hatching success. Occurrence of uninflated swim bladder was the highest (value) with exposure to 10 mg/L Cd. Swim bladder was commonly over-inflated in a mixture (0.1 mg/L Cd + 1.0 mg/L Cu) exposure. Individuals exposed to the mixture (0.1 Cd + 1.0 Cu mg/L) showed up to a 7.69% increase in swim bladder area compared to the control group. The mixtures containing 0.1 or 10 mg/L Cd, each with 1.0 mg/L Cu resulted in significantly increased of Pbx1b expression, higher than any Cd or Cu alone (p < 0.01). In the co-exposure group (0.1/10 Cd + 1.0 Cu mg/L), Pbx1b expression was found at 12 dpf but not 7 dpf in controls. Higher concentrations of Cd may progressively reduce Pbx1b expression, potentially explaining why 75% of individuals in the 10 mg/L Cd group failed to inflate their swim bladders. Additionally, the swim bladder proved to be a valuable bio-indicator for biological evaluation.

Melatonin as an immunomodulator in CD19-targeting CAR-T cell therapy: managing cytokine release syndrome.

BACKGROUND: Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood. METHODS: In this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells. RESULTS: Our findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy. CONCLUSION: The study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments.

Multi-source exposure and health risks of phthalates among university students in Northeastern China.

The endocrine disruptor phthalates (PAEs) are widely used as important chemical additives in a variety of areas around the globe. PAEs are toxic to reproduction and development and may adversely affect the health of adolescents. Risk assessments of exposure to PAEs from different sources are more reflective of actual exposure than single-source assessments. We used personal exposure parameters to estimate the dose of PAEs to 107 university students from six media (including dormitory dust, dormitory air, clothing, food, disposable food containers, and personal care products (PCPs)) and three exposure routes (including ingestion, inhalation, and dermal absorption). Individual factors and lifestyles may affect PAE exposure to varying degrees. Based on a positive matrix factorization (PMF) model, the results indicated that the main sources of PAEs in dust were indoor building materials and plastics, while PCPs and adhesives were the major sources of airborne PAEs. The relative contribution of each source to PAE exposure showed that food and air were the primary sources of dimethyl phthalate (DMP) and dibutyl phthalate (DBP). Air source contributed the most to diethyl phthalate (DEP) exposure, followed by PCPs. Food was the most significant source of diisobutyl phthalate (DiBP), benzyl butyl phthalate (BBP), and bis(2-ethylhexyl) phthalate (DEHP) exposure. Additionally, the exposure of DEHP to dust was not negligible. The ingestion pathway was the most dominant among the three exposure pathways, followed by dermal absorption. The non-carcinogenic risk of PAEs from the six sources was within acceptable limits. DEHP exhibits a low carcinogenic risk. We suggest university students maintain good hygienic and living habits to minimize exposure to PAEs.

The pan-cancer multi-omics landscape of key genes of sialylation combined with RNA-sequencing validation.

BACKGROUND: Sialylation, the process of salivary acid glycan synthesis, plays a pivotal function in tumor growth, immune escape, tumor metastasis, and resistance to drugs. However, the association between sialylation and prognosis, tumor microenvironment (TME), and treatment response in a variety of cancers remains unclear. METHODS: A comprehensive survey of the expression profile, prognostic value, and genetic and epigenetic alterations of sialylation-related genes was performed in pan-cancer. Subsequently, the single-sample gene set enrichment analysis (ssGSEA) algorithm was used to compute sialylation pathway scores in pan-cancer. Correlations of sialylation pathway scores with clinical features, prognosis, and TME were evaluated using multiple algorithms. Finally, the efficacy of the sialylation pathway score in determining the effect of immunotherapy was evaluated. The expression of sialylation-related genes were verified by RNA-sequencing. RESULTS: Significant differences were observed in sialylation-related genes expression between tumors and adjacent normal tissues for most cancer types. Sialylation pathway scores differed according to the type of tumor, where the poor prognosis was correlated with high sialylation pathway scores in uveal melanoma (UVM) and pancreatic adenocarcinoma (PAAD). In addition, sialylation pathway scores were positively associated with the ImmuneScore, StromalScore and immune-related pathways. Moreover, the level of immune cells infiltration was higher in tumors with higher sialylation pathway scores. Finally, patients with high sialylation pathway scores were more sensitive to immunotherapy. CONCLUSION: Sialylation-related genes are essential in pan-cancer. The sialylation pathway score may be used as a biomarker in oncology patients.

[Expressions and Clinical Significance of Notch1 and Hes1 in Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the expressions of Notch1 and Hes1 in diffuse large B-cell lymphoma (DLBCL), and their correlations with clinical features. METHODS: Immunohistochemistry (IHC) was performed on DLBCL samples (54 cases) and lymphadenitis tissues (20 cases) to evaluate the expressions of Notch1 and Hes1, and analyze their correlations with clinical characteristics of patients. Based on Oncomine database, the expressions of Notch1 and Hes1 mRNA and DNA were also explored. RESULTS: IHC result showed that the positive expression rates of Notch1 and Hes1 in DLBCL patients were significantly higher than those in the control group (P <0.05). In DLBCL patients, the expression of Notch1 was closely associated with B symptoms, Ann Arbor stage, lymphocyte count and the level of lactate dehydrogenase (P <0.05), while the expression level of Hes1 was significantly higher in patients with B symptoms (P <0.05). Notch+/Hes1+ expression was found in 21 DLBCL tissues (38.9%), and there was a correlation between Notch1 and Hes1 expression (r =0.296, P <0.05). Bioinformatics analysis (Oncomine database) showed that the mRNA expressions of Notch1 and Hes1 in the Brune dataset were significantly higher than those in the control tissues (P <0.05). CONCLUSION: The expressions of Notch1 and Hes1 in DLBCL are significantly higher than those in lymphadenitis, and correlated with B symptoms and Ann Arbor stage, suggesting that Notch1 and Hes1 play important roles in the occurrence and development of DLBCL.

Effects of cadmium and copper mixtures on antibiotic resistance genes in rhizosphere soil.

The evolvement and development of antibiotic resistance in microorganisms may be influenced by metals; however, it is still unclear how cadmium (Cd) and copper (Cu) combined affect the distribution and presence of antibiotic-resistance genes (ARGs) in rhizosphere soil. The aims of this research were to (1) compare the distribution patterns of bacterial communities and ARGs in response to the effects of Cd and Cu both separately and combined; (2) explore the possible mechanisms underlying the variation in soil bacterial communities and ARGs in addition to the combined effects of Cd, Cu, and various environmental variables (nutrients, pH, etc.); and (3) provide a reference for assessing the risks of metals (Cd and Cu) and ARGs. The findings showed that the multidrug resistance genes acrA and acrB and the transposon gene intI-1 were present in high relative abundance in bacterial communities. Cadmium and Cu had a substantial interaction effect on the abundance of acrA, whereas Cu had a notable main effect on the abundance of intI-1. According to the network analysis, the strong links between bacterial taxa and specific ARGs revealed that most ARGs were hosted by Proteobacteria, Actinobacteria, and Bacteroidetes. According to structural equation modeling, Cd had a larger effect on ARGs than Cu. Compared to previous analyses of ARGs, bacterial community diversity had little effect on ARGs in this study. Overall, the results may have important consequences for determining the possible hazard of soil metals and extend the understanding of how Cd and Cu co-select ARGs in rhizosphere soils.

Characteristics and health risks of population exposure to phthalates via the use of face towels.

The production of face towels is growing at an annual rate of about 4% in China, reaching 1.13 million tons by 2021. Phthalates (PAEs) are widely used in textiles, and face towels, as an important household textile, may expose people to PAEs via the skin, further leading to health risks. We collected new face towels and analyzed the distribution characterization of PAEs in them. The changes of PAEs were explored in a face towel use experiment and a simulated laundry experiment. Based on the use of face towels by 24 volunteers, we calculated the estimated daily intake (EDI) and comprehensively assessed the hazard quotient (HQ), hazard index (HI), and dermal cancer risk (DCR) of PAEs exposure in the population. PAEs were present in new face towels at total concentrations of

Loureirin C, from Chinese Dragon's Blood (Dracaena cochinchinensis S.C. Chen), is a novel selective estrogen receptor α modulator with anti-Alzheimer's disease effects.

As the incidence of Alzheimer's disease (AD) continues to rise in recent years, there are few therapeutic drugs for AD treatment with limited efficacy. AD occurs twice as often in women as that in men, partially due to the low estrogen level in women after menopause. Phytoestrogens (PEs), similar to endogenous estrogens in chemical structure with neuroprotection and fewer side effects, have good development and application prospects in AD-treatment. Loureirin C is an active ingredient isolated from Chinese Dragon's Blood (CDB) with a similar structure to 17ß-E2. In our study, we found that loureirin C targeted to ERα and had partial-agonistic activity using molecular docking prediction and dual-luciferase reporter assay. However, it is still unclear whether loureirin C has estrogenic effects in body, and whether exerts anti-AD effect through ERα. In this paper, the ERα selective inhibitor MPP or ERα specific small interfering RNA (siERα) mediated gene silencing technology were used. Besides,E-SCREEN method were used to evaluate the estrogen effects of loureirin C in vivo and in vitro. MTT assay, Western blot, real-time PCR technology and behaver tests was used to investigate the neuroprotective effect, cognitive function and the underlying mechanism. We found that loureirin C possessed estrogenic activity, had neuroprotective effects in AD cells and improved cognitive impairment in AD mice via ERα. Loureirin C may be a potential candidate for AD.

Inhalation Bioaccessibility and Risk Assessment of Metals in PM2.5 Based on a Multiple-Path Particle Dosimetry Model in the Smelting District of Northeast China.

PM2.5 can deposit and partially dissolve in the pulmonary region. In order to be consistent with the reality of the pulmonary region and avoid overestimating the inhalation human health risk, the bioaccessibility of PM2.5 heavy metals and the deposition fraction (DF) urgently needs to be considered. This paper simulates the bioaccessibility of PM2.5 heavy metals in acidic intracellular and neutral extracellular deposition environments by simulating lung fluid. The multipath particle dosimetry model was used to simulate DF of PM2.5. According to the exposure assessment method of the U.S. Environmental Protection Agency, the inhalation exposure dose threshold was calculated, and the human health risk with different inhalation exposure doses was compared. The bioaccessibility of heavy metals is 12.1−36.2%. The total DF of PM2.5 in adults was higher than that in children, and children were higher than adults in the pulmonary region, and gradually decreased with age. The inhalation exposure dose threshold is 0.04−14.2 mg·kg−1·day−1 for the non-carcinogenic exposure dose and 0.007−0.043 mg·kg−1·day−1 for the carcinogenic exposure dose. Cd and Pb in PM2.5 in the study area have a non-carcinogenic risk to human health (hazard index < 1), and Cd has no or a potential carcinogenic risk to human health. A revised inhalation health risk assessment may avoid overestimation.

CMTM Family and Gastrointestinal Tract Cancers: A Comprehensive Review.

Gastrointestinal tract cancers are a highly heterogeneous group of malignant diseases, contributing significantly to the burden of death worldwide. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTMs) plays important roles in cancer development and progression. Since the first member was cloned, there have been abundant studies on the relationships between the CMTM family and human cancers. It has been reported that the CMTM family has a large potential prognostic value for multiple cancers. Meanwhile, upregulated or downregulated expression of the family members was related to advanced tumor stage, metastasis, and overall survival. Studies have also reported that these proteins play critical roles in antitumor immunity. We performed a systematic review to sum up the latest advances of CMTM family' roles in gastrointestinal tract cancers, with a primary focus on hepatocellular carcinoma and gastric carcinoma.

Efficient extraction and antioxidant activity of polyphenols from Antrodia cinnamomea.

BACKGROUND: Antrodia cinnamomea, a rare medicinal fungus, has been increasingly studied in recent years because of its abundant secondary metabolites which are beneficial to humans. However, there is a lack of research on its polyphenols which are of good research value due to their antioxidant, anti-inflammatory, hypoglycemic and other activities. RESULTS: In this study, the effects of different extraction conditions on the yield of its polyphenols were investigated. Deep-Eutectic Solvents composed of choline chloride and malonic acid had the best extraction efficiency, with the optimal extraction conditions being as follows: a solid-liquid ratio of 40 mg/mL, an extraction temperature of 55 °C, an extraction time of 70 min and a DES with 20% water content. Under these conditions, the extraction yield of polyphenols reached 22.09 mg/g which was about 2 times that of alcohol-based extraction (10.95 mg/g). In vitro antioxidant test results further showed that polyphenols from A. cinnamomea had strong antioxidant activities. When the concentration of polyphenols reached 0.1 mg/mL of polyphenols, the scavenging activity of free radical basically reached its maximum, with values of 94.10%, 83.34% and 95.42% for DPPH, ABTS+ and ·OH scavenging. In this case, the corresponding IC50 values were 0.01, 0.014 and 0.007 mg/mL, respectively. CONCLUSIONS: This study lays the foundation for the efficient extraction and application of polyphenols from A. cinnamomea.