Isolation and Culture of Primary Human Mammary Epithelial Cells.

The mammary gland is a fundamental structure of the breast and plays an essential role in reproduction. Human mammary epithelial cells (HMECs), which are the origin cells of breast cancer and other breast-related inflammatory diseases, have garnered considerable attention. However, isolating and culturing primary HMECs in vitro for research purposes has been challenging due to their highly differentiated, keratinized nature and their short lifespan. Therefore, developing a simple and efficient method to isolate and culture HMECs is of great scientific value for the study of breast biology and breast-related diseases. In this study, we successfully isolated primary HMECs from small amounts of mammary tissue by digestion with a mixture of enzymes combined with an initial culture in 5% fetal bovine serum-DMEM containing the Rho-associated kinase (ROCK) inhibitor Y-27632, followed by culture expansion in serum-free keratinocyte medium. This approach selectively promotes the growth of epithelial cells, resulting in an optimized cell yield. The simplicity and convenience of this method make it suitable for both laboratory and clinical research, which should provide valuable insights into these important areas of study.

A potent new-scaffold androgen receptor antagonist discovered on the basis of a MIEC-SVM model.

Prostate cancer (PCa) is the second most prevalent malignancy among men worldwide. The aberrant activation of androgen receptor (AR) signaling has been recognized as a crucial oncogenic driver for PCa and AR antagonists are widely used in PCa therapy. To develop novel AR antagonist, a machine-learning MIEC-SVM model was established for the virtual screening and 51 candidates were selected and submitted for bioactivity evaluation. To our surprise, a new-scaffold AR antagonist C2 with comparable bioactivity with Enz was identified at the initial round of screening. C2 showed pronounced inhibition on the transcriptional function (IC50 = 0.63 µM) and nuclear translocation of AR and significant antiproliferative and antimetastatic activity on PCa cell line of LNCaP. In addition, C2 exhibited a stronger ability to block the cell cycle of LNCaP than Enz at lower dose and superior AR specificity. Our study highlights the success of MIEC-SVM in discovering AR antagonists, and compound C2 presents a promising new scaffold for the development of AR-targeted therapeutics.

Cancer progression and tumor hypercoagulability: a platelet perspective.

Venous thromboembolism, which is common in cancer patients and accompanies or even precedes malignant tumors, is known as cancer-related thrombosis and is an important cause of cancer- associated death. At present, the exact etiology of the elevated incidence of venous thrombosis in cancer patients remains elusive. Platelets play a crucial role in blood coagulation, which is intimately linked to the development of arterial thrombosis. Additionally, platelets contribute to tumor progression and facilitate immune evasion by tumors. Tumor cells can interact with the coagulation system through various mechanisms, such as producing hemostatic proteins, activating platelets, and directly adhering to normal cells. The relationship between platelets and malignant tumors is also significant. In this review article, we will explore these connections.

Approaching the Ideal Linearity in Epitaxial Crystalline-Type Memristor by Controlling Filament Growth.

Brain-inspired neuromorphic computing has attracted widespread attention owing to its ability to perform parallel and energy-efficient computation. However, the synaptic weight of amorphous/polycrystalline oxide based memristor usually exhibits large nonlinear behavior with high asymmetry, which aggravates the complexity of peripheral circuit system. Controllable growth of conductive filaments is highly demanded for achieving the highly linear conductance modulation. However, the stochastic behavior of the filament growth in commonly used amorphous/polycrystalline oxide memristor makes it very challenging. Here, the epitaxially grown Hf0.5Zr0.5O2-based memristor with the linearity and symmetry approaching ideal case is reported. A layer of Cu nanoparticles is inserted into epitaxially grown Hf0.5Zr0.5O2 film to form the grain boundaries due to the breaking of the epitaxial growth. By combining with the local electric field enhancement, the growth of filament is confined in the grain boundaries due to the fact that the diffusion of oxygen vacancy in crystalline lattice is more difficult than that in the grain boundaries. Furthermore, the decimal operation and high-accuracy neural network are demonstrated by utilizing the highly linear and multi-level conductance modulation capacity. This method opens an avenue to control the filament growth for the application of resistance random access memory (RRAM) and neuromorphic computing.

GJB3: a comprehensive biomarker in pan-cancer prognosis and immunotherapy prediction.

BACKGROUND: A wide range of connexins are situated between normal-normal cells, cancer-cancer cells, and cancer-normal cells. Abnormalities in connexin expression are typically accompanied by cancer development; however, no systematic studies have examined the role of Gap Junction Protein Beta 3 (GJB3) in the context of tumor progression and immunity, especially when considering a broad range of cancer types. METHODS: In this study, data on GJB3 expression were gathered from Genotype-Tissue Expression, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas databases. Then, we analyzed the relationship between GJB3 expression and tumor characteristics. In vitro experiments using colony formation, EdU, CCK8, transwell migration assays, immunohistochemistry and western blot were performed to investigate the function of GJB3 in tumor progression of various cell lines. A drug sensitivity analysis of GJB3 was performed using the Genomics of Drug Sensitivity in Cancer database. RESULT: Our findings demonstrate that GJB3 is widely expressed in various cancers and correlates significantly with disease stages, patient survival, immunotherapy response, and pharmaceutical guidance. Additionally, GJB3 plays a role in different cancer pathways, as well as in different immune and molecular subtypes of cancer. Co-expression of GJB3 with immune checkpoint genes was observed. Further experiments showed that knockdown of GJB3 inhibited the PI3K/AKT pathway and resulted in reduced proliferation, migration, and viability of different cancer cells. CONCLUSION: Overall, GJB3 shows potential as a molecular biomarker and therapeutic target for various cancers, particularly lung adenocarcinomas, mesothelioma, pancreatic adenocarcinoma. Thus, GJB3 may represent a new therapeutic target for a wide range of cancers.

Whole-brain Mapping of Inputs and Outputs of Specific Orbitofrontal Cortical Neurons in Mice.

The orbitofrontal cortex (ORB), a region crucial for stimulus-reward association, decision-making, and flexible behaviors, extensively connects with other brain areas. However, brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized. Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons. We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions, albeit with quantitative variations, particularly in somatomotor areas and medial groups of the dorsal thalamus. By counting parvalbumin (PV) or somatostatin (SST) interneurons innervated by neurons in specific ORB subregions, we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons. These results provide insights into understanding and investigating the function of specific ORB neurons.

Percutaneous transhepatic cholangioscopy-assisted biliary polypectomy for local palliative treatment of intraductal papillary neoplasm of the bile duct.

BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a premalignant biliary-type epithelial neoplasm with intraductal papillary or villous growth. Currently reported local palliative therapeutic modalities, including endoscopic nasobiliary drainage, stenting and biliary curettage, endoscopic biliary polypectomy, percutaneous biliary drainage, laser ablation, argon plasma coagulation, photodynamic therapy, and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and disadvantages. We have applied percutaneous transhepatic cholangioscopy (PTCS)-assisted biliary polypectomy (PTCS-BP) technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since 2010. AIM: To assess the technical feasibility, efficacy, and safety of PTCS-BP for local palliative treatment of IPNB. METHODS: Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were included. PTCS-BP was performed by using a half-moon type snare with a soft stainless-steel wire, and the tumor was snared and resected with electrocautery. The primary outcome was its feasibility, indicated by technical success. The secondary outcomes were efficacy, including therapeutic success, curative resection, and clinical success, and safety. RESULTS: Five patients (four with mucin-hypersecreting cast-like type and one with polypoid type IPNB) were included. Low- and high-grade intraepithelial neoplasia (HGIN) and recurrent IPNB with invasive carcinoma were observed in one, two, and two patients, respectively. Repeated cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type IPNB. All five patients achieved technical success of PTCS-BP. Four patients (three with mucin-hypersecreting cast-like type and one with polypoid type IPNB) obtained therapeutic success; one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN had residual tumors. All four patients with mucin-hypersecreting IPNB achieved clinical success. The patient with polypoid type IPNB achieved curative resection. There were no PTCS-BP-related serious adverse events. CONCLUSION: PTCS-BP appears to be feasible, efficacious, and safe for local palliative treatment of both mucin-hypersecreting cast-like and polypoid type IPNB.

Glycoprotein non-metastatic melanoma protein B (GPNMB) protects against neuroinflammation and neuronal loss in pilocarpine-induced epilepsy via the regulation of microglial polarization.

Epilepsy is a progressive neurodegenerative disease highlighted by recurrent seizures, neuroinflammation, and the loss of neurons. Microglial dysfunction is commonly found in epileptic foci and contributes to neuroinflammation in the initiation and progression of epilepsy. Glycoprotein non-metastatic melanoma protein B (GPNMB), a transmembrane glycoprotein, has been involved in the microglial activation and neuroinflammation response. The present study investigated the functional significance of GPNMB in epilepsy. A proven model of epilepsy was established by intraperitoneal injection of pilocarpine to male Sprague Dawley rats. Lentivirus vectors carrying GPNMB or GPNMB short hairpin RNA (shGPNMB) were injected into the hippocampus to induce overexpression or knockdown of GPNMB. GPNMB expression was significantly upregulated and overexpression of GPNMB in the hippocampus reduced seizure activity and neuronal loss after status epilepticus (SE). We here focused on the effects of GPNMB deficiency on neuronal injury and microglia polarization 28 days after SE. GPNMB knockdown accelerated neuronal damage in the hippocampus, evidenced by increased neuron loss and neuronal cell apoptosis. Following GPNMB knockdown, M1 polarization (iNOS) and secretion of pro-inflammatory cytokines IL-6, IL-1ß, and TNF-α were increased, and M2 polarization (Arg1) and secretion of anti-inflammatory cytokines IL-4, IL-10, and TGF-ß were decreased. BV2 cells were used to further confirm the regulatory role of GPNMB in modulating phenotypic transformations and inflammatory cytokine expressions in microglia. In conclusion, these results indicated that GPNMB suppressed epilepsy through repression of hippocampal neuroinflammation, suggesting that GPNMB might be considered the potential neurotherapeutic target for epilepsy management and play a protective role against epilepsy by modulating the polarization of microglia.

A case of primary breast angiosarcoma diagnosed by multimodal ultrasound imaging with literature review.

Primary Breast Angiosarcoma (PBA) is an exceptionally rare form of breast cancer, accounting for less than 0.05% of all breast cancers. It is characterized by a high level of malignancy, invasiveness, and has a prognosis that is typically poor. The lack of distinctive clinical features makes it prone to underdiagnosis and misdiagnosis. This study retrospectively examines a case utilizing multimodal ultrasound imaging techniques (including 2D ultrasound, contrast-enhanced ultrasound, and ultrasound elastography) for diagnosing PBA. Furthermore, the study reviews relevant literature to summarize the ultrasound characteristics of PBA, with the aim of improving understanding of this elusive condition.

Efficacy and Toxicity of Moderately Hypofractionated Radiation Therapy with Helical TomoTherapy Versus Conventional Radiation Therapy in Patients with Unresectable Stage III Non-Small Cell Lung Cancer Receiving Concurrent Chemotherapy: A Multicenter, Randomized Phase 3 Trial.

PURPOSE: The standard treatment schedule for unresectable stage III non-small cell lung cancer (NSCLC) is chemotherapy with concurrent radiation therapy (60 Gy delivered in 30 fractions), although moderately hypofractionated radiation therapy (Hypo-RT) has also been considered as an alternative strategy. This study aimed to compare the efficacy and toxicity of moderately Hypo-RT with helical TomoTherapy versus conventionally fractionated radiation therapy (Con-RT) in patients with unresectable stage III NSCLC receiving concurrent chemotherapy. METHODS AND MATERIALS: In this randomized, multicenter, nonblinded phase 3 clinical trial, eligible patients were randomised at a 1:1 ratio to either the Hypo-RT group (60 Gy in 20 fractions) or Con-RT group (60 Gy in 30 fractions). All patients received 2 cycles of concurrent platinum-based chemotherapy plus 2 cycles of consolidation therapy. The primary endpoint was 3-year overall survival (OS) in the intention-to-treat population. The secondary endpoints were progression-free survival and treatment-related adverse events. RESULTS: A total of 146 patients were enrolled from July 27, 2018, to November 1, 2021. The median follow-up was 46 months. The 3-year OS rates in the Hypo-RT and Con-RT groups were 58.4% and 38.4%, respectively (P = .02). The median OS from randomisation was 41 months in the Hypo-RT group and 30 months in the Con-RT group (hazard ratio, 0.61; 95% confidence interval, 0.40-0.94; P = .02). There was no significant difference in the rates of grade ≥2 treatment-related adverse events between the 2 groups. CONCLUSIONS: Moderately Hypo-RT using helical TomoTherapy may improve OS in patients with unresectable stage III NSCLC, while maintaining toxicity rates.

Insulin-like growth factor-1 promotes the testicular sperm production by improving germ cell survival and proliferation in high-fat diet-treated male mice.

BACKGROUND: A decrease in semen volume among men is comparable to the rising prevalence of obesity worldwide. The anabolic hormone insulin-like growth factor-1 (IGF-1) can promote proliferation and differentiation in cultured mouse spermatogonial stem cells and alleviate abnormal in vitro spermatogenesis. Additionally, serum IGF-1 level is negatively correlated with body mass index. Whereas the role of IGF-1 in the sperm production in obese men remains unclear. OBJECTIVE: To investigate the therapeutic effect and potential mechanism of IGF-1 on spermatogenesis of high-fat diet (HFD)-induced obesity mice. METHODS: An HFD-induced obesity mouse model was established. Alterations in testicular morphology, sperm count, proliferation, and apoptosis were observed by H&E staining,immunohistochemistry, immunofluorescence, and Western blotting. Exogenous recombinant IGF-1 was administered to obese mice to investigate the correlations between altered testicular IGF-1 levels and sperm production. RESULTS: The sperm count was reduced, the testicular structure was disordered, and sex hormone levels were abnormal in HFD-fed mice compared with normal diet-fed mice. The expression of proliferation-related antigens such as proliferating cell nuclear antigen (PCNA) and Ki-67 was decreased, while that of proapoptotic proteins such as c-caspase3 was increased in testes from HFD-fed mice. Most importantly, the phosphorylation of insulin-like growth factor-1 receptor (IGF-1R) in testes was decreased due to reductions in IGF-1 from hepatocytes and Sertoli cells. Recombinant IGF-1 alleviated these functional impairments by promoting IGF-1R, Akt, and Erk1/2 phosphorylation in the testes. CONCLUSIONS: Insufficient IGF-1/IGF-1R signaling is intimately linked to damaged sperm production in obese male mice. Exogenous IGF-1 can improve survival and proliferation as well as sperm production. This study provides a novel theoretical basis and a target for the treatment of obese men with oligozoospermia.

Developmental characteristics of aggregated lymphoid nodules area in the abomasum of fetal Bactrian camels (Camelus bactrianus).

BACKGROUND: Bactrian camel is one of the important economic animals in northwest China. They live in arid desert, and their gestation period is about 13 months, which is longer than other ruminants (such as cattle and sheep). The harsh living conditions have made its unique histological characteristics a research focus. Aggregated lymphoid nodules area (ALNA) in the abomasum of Bactrian camels, as one of the most important sites for the induction of the immune response, provide a comprehensive and effective protective role for the organism, and their lack of information will affect the feeding management, reproduction and epidemic prevention of Bactrian camels. In this study, the histological characteristics of the fetal ALNA in the abomasum of Bactrian camels at different developmental gestation have been described by using light microscopy and histology . RESULTS: The ALNA in the abomasum of the Chinese Alashan Bactrian camel is a special immune structure that was first discovered and reported by Wen-hui Wang. To further establish the developmental characteristics of this special structure in the embryonic stage, the abomasum ALNA of 8 fetuses of Alashan Bactrian camels with different gestational ages (5~13 months) were observed and studied by anatomy and histology. The results showed that the aggregation of reticular epithelial cells (RECs) surrounded by a very small number of lymphoid cells was detected for the first time in the abomasum of fetal camel at 5 months gestation, which was presumed to be primitive ALNA. At 7 months gestation, the reticular mucosal folds region (RMFR) appeared, but the longitudinal mucosal folds region (LMFR) was not significant, and histological observations showed that there were diffusely distributed lymphocytes around the RECs. At 10months gestation, RMFR and LMFR were clearly visible, lymphoid follicles appeared in histological observation, lymphocytes proliferated vigorously. By 13 months, the volume of lymphoid follicles increased, forming the subepithelial dome (SED), and there was a primitive interfollicular area between the lymphoid follicles, which contained high endothelial vein (HEV), but no germinal center (GC) was found. In summary, ALNA of Bactrian camels is not fully mature before birth. CONCLUSIONS: Generally, the small intestine PPs of ruminants (such as cattle and sheep) is already mature before birth, while the ALNA in the abomasum of Bactrian camels is not yet mature in the fetal period. During the development of ALNA in Bactrian camel, the development of lymphoid follicles extends from submucosa to Lamina propria. Interestingly, the deformation of FAE changes with age from simple columnar epithelium at the beginning of pregnancy to Simple cuboidal epithelium, which is opposite to the FAE deformation characteristics of PPs in the small intestine of fetal cattle and sheep. These results are the basis of further research on the specificity of ALNA in the abomasum of Bactrian camels.

Clinical performance and utility of a noninvasive urine-based methylation biomarker: TWIST1/Vimentin to detect urothelial carcinoma of the bladder.

Traditional clinical modalities for diagnosing bladder urothelial carcinoma (BUC) remain limited due to their invasive nature, significant costs, discomfort associated with cystoscopy, and low sensitivity to urine cytology. Therefore, there is an urgent need to identify highly sensitive, specific, and noninvasive biomarkers for the early detection of this neoplasm. Hypermethylated TWIST1/Vimentin promoter may be a noninvasive biomarker using urine sample. We assessed the TWIST1/Vimentin promoter methylation status in urine samples using the Methylated Human TWIST1 and Vimentin Gene Detection Kit (Jiangsu MicroDiag Biomedicine Co., Ltd., China). The samples were collected from five groups: group 1 consisted of patients with BUC, group 2 contained other patients with urologic tumors, group 3 consisted of patients with benign diseases (e.g., urinary tract infections, lithiasis, and benign prostatic hyperplasia), Group 4 included UTUC (upper tract urothelial carcinoma) patients and group5 comprised healthy individuals. The study encompassed 77 BUC patients, and we evaluated the degree of methylation of the TWIST1/Vimentin gene in their urine samples. Notably, TWIST1/Vimentin positivity was significantly elevated in comparison to groups 2, 3 and 5 (all p < 0.001) at a rate of 77.9%, but no significant difference was observed when compared to group 4. In the relationship between TWIST1/Vimentin methylation and clinicopathological features of BC patients from our center, we found there was no significant association between TWIST1/Vimentin status and proteinuria and/or hematuria, and hypermethylation of TWIST1 / VIM genes was found in both high and low tumor grade and in both non-muscle invasive bladder cancer (stages Tis, Ta, or T1) and muscle-invasive bladder cancer (stage T2 or above). In the multivariable analysis for cancer detection, a positive TWIST1/Vimentin methylation were significantly linked to a heightened risk of BC. Moreover, TWIST1/Vimentin promoter methylation demonstrated an ability to detect BUC in urine samples with a sensitivity of 78% and a specificity of 83%. Our findings reveal that hypermethylation of the TWIST1/Vimentin promoter occurs in bladder urothelial carcinoma, and its high sensitivity and specificity suggest its potential as a screening and therapeutic biomarker for urothelial carcinoma of the bladder.

MicroRNA-1258 suppresses oxidative stress and inflammation in septic acute lung injury through the Pknox1-regulated TGF-ß1/SMAD3 cascade.

AIM: The study was to clarify the mechanism of miR-1258 targeting Prep1 (pKnox1) to control Transforming Growth Factor ß1 (TGF-ß1)/SMAD3 pathway in septic Acute Lung Injury (ALI)-induced oxidative stress and inflammation. METHODS: BEAS-2B cells and C57BL/6 mice were used to make in vitro and in vivo septic ALI models, respectively. miR-1258 expression was checked by RT-qPCR. After transfection in the in vitro experimental model, inflammation, oxidative stress, viability, and apoptosis were observed through ELISA, MTT, and flow cytometry. RESULTS: In the in vivo model after miR-1258 overexpression treatment, inflammation, oxidative stress, and lung injury were further investigated. The targeting relationship between miR-1258 and Pknox1 was tested. Low miR-1258 was expressed in septic ALI patients, LPS-treated BEAS-2B cells, and mice. Upregulated miR-1258 prevented inflammation, oxidative stress, and apoptosis but enhanced the viability of LPS-treated BEAS-2B cells. The impact of upregulated miR-1258 on LPS-treated BEAS-2B cells was mitigated by inhibiting Pknox1 expression. MiR-1258 overexpression had the alleviating effects on inflammation, oxidative stress, and lung injury of LPS-injured mice through suppressing Pknox1 expression and TGF-ß1/SMAD3 cascade activation. CONCLUSIONS: The study concludes that miR-1258 suppresses oxidative stress and inflammation in septic ALI through the Pknox1-regulated TGF-ß1/SMAD3 cascade.

N6-methyladenosine-modified circSLCO1B3 promotes intrahepatic cholangiocarcinoma progression via regulating HOXC8 and PD-L1.

BACKGROUND: Refractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality and poor prognosis. Important function invests circRNAs with tremendous potential in biomarkers and therapeutic targets. Nevertheless, it is still unknown how circRNAs contribute to the evolution of ICC. METHODS: CircRNAs in paired ICC and adjacent tissues were screened by circRNAs sequencing. To explore the impact of circRNAs on ICC development, experiments involving gain and loss of function were conducted. Various experimental techniques, including quantitative real-time PCR (qPCR), western blotting, RNA immunoprecipitation (RIP), luciferase reporter assays, RNA pull-down, chromatin immunoprecipitation (ChIP), ubiquitination assays and so on were employed to identify the molecular regulatory role of circRNAs. RESULTS: Herein, we reported a new circRNA, which originates from exon 9 to exon 15 of the SLCO1B3 gene (named circSLCO1B3), orchestrated ICC progression by promoting tumor proliferation, metastasis and immune evasion. We found that the circSLCO1B3 gene was highly overexpressed in ICC tissues and related to lymphatic metastasis, tumor sizes, and tumor differentiation. Mechanically, circSLCO1B3 not only promoted ICC proliferation and metastasis via miR-502-5p/HOXC8/SMAD3 axis, but also eradicated anti-tumor immunity via suppressing ubiquitin-proteasome-dependent degradation of PD-L1 by E3 ubiquitin ligase SPOP. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circSLCO1B3 and stabilizes its expression. Our findings indicate that circSLCO1B3 is a potential prognostic marker and therapeutic target in ICC patients. CONCLUSIONS: Taken together, m6A-modified circSLCO1B3 was correlated with poor prognosis in ICC and promoted ICC progression not only by enhancing proliferation and metastasis via potentiating HOXC8 expression, but also by inducing immune evasion via antagonizing PD-L1 degradation. These results suggest that circSLCO1B3 is a potential prognostic marker and therapeutic target for ICC.

The future of sex and gender in research.

Our understanding of sex and gender evolves. We asked scientists about their work and the future of sex and gender research. They discuss, among other things, interdisciplinary collaboration, moving beyond binary conceptualizations, accounting for intersecting factors, reproductive strategies, expanding research on sex-related differences, and sex's dynamic nature.

Less is more: A new strategy combining nanomaterials and PGPB to promote plant growth and phytoremediation in contaminated soil.

Novel combination strategies of nanomaterials (NMs) and plant growth-promoting bacteria (PGPB) may facilitate soil remediation and plant growth. However, the efficiency of the NM-PGPB combination and interactions among NMs, PGPB, and plants are still largely unknown. We used multiwalled carbon nanotubes (MWCNTs) and zero-valent iron (nZVI) combined with Bacillus sp. PGP5 to enhance the phytoremediation efficiency of Solanum nigrum on heavy metal (HM)-contaminated soil. The NM-PGPB combination showed the best promoting effect on plant growth, which also had synergistic effects on the bioaccumulation of HMs in S. nigrum. The MWCNT-PGP5 combination increased the Cd, Pb, and Zn removal efficiency of S. nigrum by 62.03%, 69.44%, and 61.31%, respectively. The underlining causes of improved plant growth and phytoremediation by NMs-PGPB combination were further elucidated. NM application promoted PGPB survival in soil. Compared with each single application, the combined application minimized disturbance to plant transcription levels and rhizosphere microbial community, resulting in the best performance on soil remediation and plant growth. The NM-PGPB-induced changes in the microbial community and root gene expression were necessary for plant growth promotion. This work reveals the "less is more" advantage of the NM-PGPB combination in soil remediation, providing a new strategy for soil management.

Generation of skyrmions by combining thermal and spin-orbit torque: breaking half skyrmions into skyrmions.

Skyrmions, swirling spin textures with topologically protected stability and low critical driven-current density, can be generated from the stripe domain with current pulses, bringing them closer to practical applications in racetrack memory. However, the mechanism of this topological transition from the stripe domain to the skyrmion remains unclear because the transition process occurs at a nanosecond timescale, giving rise to difficulties in observing this process using imaging tools. In this study, we controlled the domain wall - skyrmion transition by combining Joule heating with spin-orbit torque (SOT) and experimentally observed the details of this process, by which we confirmed the mechanism: the spatial variation of the topological charge density induces half skyrmions branching from the stripe domains, and these half skyrmions overcome the surface tension and break away from the stripe domain, resulting in the generation of skyrmions. The details were observed by employing Joule heating to overcome the pinning effect and manipulating the strength of the SOT to induce the branching and breaking of half skyrmions. These findings offer new insights into skyrmion generation and serve as an important step towards the development of highly efficient devices for processing and computing based on skyrmionics.

Anti-cancer agent piperlongumine is an inhibitor of transient receptor potential melastatin 7 channel in oral squamous cell carcinoma.

OBJECTIVES: To elucidate the association between the anticancer activities of piperlongumine (PL) and its potential target, transient receptor potential melastatin 7 channel (TRPM7), in oral squamous cell carcinoma (OSCC). METHODS: The expression levels and electrical characteristics of TRPM7 as well as cell viability in response to various PL treatments were investigated in the OSCC cell line Cal27. RESULTS: PL treatment resulted in a concentration- and time-dependent reduction in TRPM7 mRNA and protein expression in Cal27 cells. Furthermore, PL treatment inhibited TRPM7-like rectifying currents in Cal27 cells; however, this inhibition was less effective than that of the TRPM7 antagonist waixenicin A. Rapid perfusion and washout experiments revealed an immediate inhibitory effect of PL on TRPM7-like currents. The antagonistic effect of PL occurred within 1 min and was not completely reversed following washout. Notably, the extracellular Ca2+ concentration still influenced PL-induced changes in the TRPM7-like current, indicating that PL can directly but gently antagonize the TRPM7 channel. Functional changes in TRPM7 correlated with the observed antiproliferative and cytotoxic effects of PL in Cal27 cells. CONCLUSIONS: These findings suggest that PL exhibits potent inhibitory effects on TRPM7 and exerts its anti-cancer effects by downregulating TRPM7 expression and antagonizing channel currents.