An unprotected vulnerable relict subtropical conifer-Keteleeria evelyniana: Its forests, populations, growth and endangerment by invasive alien plant species in China.

Relict subtropical coniferous forests in China face severe fragmentation, resulting in declining populations, and some are under significant threat from invasive alien species. Despite the crucial importance of understanding forest dynamics, knowledge gaps persist, particularly regarding the impact of invasive plants on vulnerable natives like Keteleeria evelyniana. In this study, we investigated the impact of invasive plants on the regeneration of forests dominated by K. evelyniana, a subtropical relict species in southwestern China. For this purpose, we characterized forest dynamics of 160 forest plots featuring K. evelyniana as the primary dominant species and determined whether the presence of invasive plants was correlated with regeneration of K. evelyniana. We identified four distinct forest types in which K. evelyniana was dominant. We found that radial growth of K. evelyniana trees is faster in younger age-classes today than it was for older trees at the same age. The population structure of K. evelyniana in each forest type exhibited a multimodal age-class distribution. However, three forest types lacked established saplings younger than 10 years old, a situation attributed to the dense coverage of the invasive alien Ageratina adenophora. This invasive species resulted in a reduction of understory species diversity. Additionally, our analysis uncovered a significant negative correlation in phylogenetic relatedness (net relatedness index) between native and invasive alien plant species in eastern Yunnan. This suggests closely related invasive species face heightened competition, hindering successful invasion. Taken together, our findings indicate that successful establishment and habitat restoration of K. evelyniana seedling/saplings require effective measures to control invasive plants.

Downregulation of CIAPIN1 regulates the proliferation, migration and glycolysis of breast cancer cells via inhibition of STAT3 pathway.

Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a protein that regulates apoptosis and programmed cell death. This research aims to evaluate its potential role in inhibiting breast cancer cell proliferation, migration, and glycolysis and uncover its underlying molecular mechanism. We collected breast cancer tissue samples from eight patients between January 2019 and June 2023 in our Hospital to analyse CIAPIN1 expression. We transfected human breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-453, and MDA-MB-468) with siRNA of CIAPIN1. Finally, we determined protein expression using RT-qPCR and Western blotting. CIAPIN1 expression was elevated in both breast cancer tissue and serum. Overexpression of CIAPIN1 detected in the breast cancer cell lines MCF7 and MDA-MB-468. In addition, CIAPIN1 overexpression increased cell proliferation and migration rate. CIAPIN1 downregulation suppressed cell proliferation while elevated cellular apoptosis, reactive oxygen species (ROS) production and oxidative stress in breast cancer cells. Moreover, CIAPIN1 inhibition remarkably suppressed pyruvate, lactate and adenosine triphosphate (ATP) production and reduced the pyruvate kinase M2 (PKM2) protein expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) in breast cancer cells. Downregulation of CIAPIN1 suppresses cell proliferation, migration and glycolysis capacity in breast cancer cells by inhibiting the STAT3/PKM2 pathway.

Glutathione-Disrupting Nanotherapeutics Potentiate Ferroptosis for Treating Luminal Androgen Receptor-Positive Triple-Negative Breast Cancer.

The refractory luminal androgen receptor (LAR) subtype of triple-negative breast cancer (TNBC) patients is challenged by significant resistance to neoadjuvant chemotherapy and increased immunosuppression. Regarding the distinct upregulation of glutathione (GSH) and glutathione peroxidase 4 (GPX4) in LAR TNBC tumors, we herein designed a GSH-depleting phospholipid derivative (BPP) and propose a BPP-based nanotherapeutics of RSL-3 (GDNS), aiming to deplete intracellular GSH and repress GPX4 activity, thereby potentiating ferroptosis for treating LAR-subtype TNBC. GDNS treatment drastically downregulated the expression of GSH and GPX4, resulting in a 33.88-fold enhancement of lipid peroxidation and significant relief of immunosuppression in the 4T1 TNBC model. Moreover, GDNS and its combination with antibody against programed cell death protein 1 (antiPD-1) retarded tumor growth and produced 2.83-fold prolongation of survival in the LAR-positive TNBC model. Therefore, the GSH-disrupting GDNS represents an encouraging strategy to potentiate ferroptosis for treating refractory LAR-subtype TNBC.

LIMK1 promotes the development of cervical cancer by up-regulating the ROS/Src-FAK/cofilin signaling pathway.

OBJECTIVE: In this study, we investigated the mechanism of action of LIMK1 in cervical cancer progression. METHODS: The biological role of LIMK1 in regulating the growth, invasion, and metastasis of cervical cancer was studied in SiHa, CaSki cells and nude mice tumor models. The role of LIMK1 in the growth of cervical cancer was evaluated by HE staining. The role of LIMK1 in the invasion, metastasis, and proliferation of cervical cancer was evaluated by cell scratch, Transwell, and monoclonal experiments. The interaction among LIMK1, ROS, and Src was evaluated by Western blotting. The effects of regulating ROS and p-Src expression on LIMK1 in the migration/invasion and proliferation of cervical cancer cells were evaluated through cellular functional assays. RESULTS: Overexpression of LIMK1 promoted tumor growth in nude mice. Cell scratch, Transwell, and monoclonal experiments suggested that LIMK1 promoted the invasion, metastasis, and proliferation of cervical cancer cells. Western blotting suggested that LIMK1 can promote the expression of ROS-related proteins NOX2, NOX4, p-Src, and downstream proteins p-FAK, p-ROCK1/2, p-Cofilin-1, F-actin and inhibit the expression of p-SHP2 protein. Correction experiments showed that LIMK1 regulated the expression of p-FAK and p-Cofilin-1 proteins by regulating ROS and p-Src. Through the detection of cervical cancer cell functions, it was found that the activation of ROS and p-Src induced by LIMK1 is an early event that promotes the migration, proliferation, and invasion of cervical cancer cells. CONCLUSIONS: LIMK1 promotes the expression of F-actin and promotes the development of cervical cancer by regulating the oxidative stress/Src-mediated p-FAK/p-ROCK1/2/p-Cofilin-1 pathway.

A tonoplast-localized TPK-type K+ transporter (TPKa) regulates potassium accumulation in tobacco.

Potassium ion (K+) is one of the most essential nutrients for the growth and development of tobacco (Nicotiana tabacum L.), however, the molecular regulation of K+ concentration in tobacco remains unclear. In this study, a two-pore K (TPK) channel gene NtTPKa was cloned from tobacco, and NtTPKa protein contains the unique K+ selection motif GYGD and its transmembrane region primarily locates in the tonoplast membrane. The expression of NtTPKa gene was significantly increased under low-potassium stress conditions. The concentrations of K+ in tobacco were significantly increased in the NtTPKa RNA interference lines and CRISPR/Cas9 knockout mutants. In addition, the transport of K+ by NtTPKa was validated using patch clamp technique, and the results showed that NtTPKa channel protein exclusively transported K+ in a concentration-dependent manner. Together, our results strongly suggested that NtTPKa is a key gene in maintaining K+ homeostasis in tobacco, and it could provide a new genetic resource for increasing the concentration of K+ in tobacco.

Alleviating sweetpotato salt tolerance through exogenous glutathione and melatonin: A profound mechanism for active oxygen detoxification and preservation of photosynthetic organs.

Salt stress profoundly impacts sweetpotato production. Exogenous glutathione (GSH) and melatonin (MT) promoted plant growth under stress, but their specific roles and mechanisms in sweetpotato salt tolerance need exploration. This study investigated GSH and MT's regulatory mechanisms in sweetpotato under salt stress. Salt stress significantly reduces both growth and biomass by hindering photosynthesis, root traits, K+ content, and K+/Na+ balance, leading to oxidative stress and excessive hydrogen peroxide (H2O2), superoxide ion (O2•-), and malondialdehyde (MDA) production and Na+ accumulation. Nevertheless, GSH (2 mM) and MT (25 µM) pre-treatments effectively mitigated salt-induced oxidative damage and protected the plasma membrane. They reduced osmotic pressure by enhancing K+ uptake, K+/Na+ regulation, osmolyte accumulation, and reducing Na+ accumulation. Improved stomatal traits, chloroplast and grana lamella preservation, and maintenance of mesophyll cells, cell wall, and mitochondrial structure were observed with GSH and MT pre-treatments under salt stress, therefore boosting the photosynthetic system and enhancing plant growth and biomass. Moreover, the findings also indicate that the positive outcomes of GSH and MT pre-treatments result from elevated antioxidant levels, enhanced enzymatic activity, and upregulated expression of sodium hydrogen exchanger 2 (NHX2), K+transporter 1 (AKT1), and cation/H+exchanger (CHX), CBL-interacting protein kinase 1 (CIPK1), and antioxidant enzyme genes. These mechanisms enhance structural stability in photosynthesis and reduce salt stress. Evidently, MT pre-treatment exhibited superior effects compared to GSH. These findings provide a firm theoretical basis for employing GSH and MT to enhance salt tolerance in sweetpotato cultivation.

Extracellular Matrix-Trapped Bioinspired Lipoprotein Prolongs Tumor Retention to Potentiate Antitumor Immunity.

The immunomodulatory effects of many therapeutic agents are significantly challenged by their insufficient delivery efficiency and short retention time in tumors. Regarding the distinctively upregulated fibronectin (FN1) and tenascin C (TNC) in tumor stroma, herein a protease-activated FN1 and/or TNC binding peptide (FTF) is designed and an extracellular matrix (ECM)-trapped bioinspired lipoprotein (BL) (FTF-BL-CP) is proposed that can be preferentially captured by the TNC and/or FN1 for tumor retention, and then be responsively dissociated from the matrix to potentiate the antitumor immunity. The FTF-BL-CP treatment produces a 6.96-, 9.24-, 6.72-, 7.32-, and 6.73-fold increase of CD3+CD8+ T cells and their interferon-γ-, granzyme B-, perforin-, and Ki67-expressing subtypes versus the negative control, thereby profoundly eliciting the antitumor immunity. In orthotopic and lung metastatic breast cancer models, FTF-BL-CP produces notable therapeutic benefits of retarding tumor growth, extending survivals, and inhibiting lung metastasis. Therefore, this ECM-trapping strategy provides an encouraging possibility of prolonging tumor retention to potentiate the antitumor immunity for anticancer immunotherapy.

Changes in physicochemical properties and microbial community succession during leaf stacking fermentation.

Leaf stacking fermentation involves enzymatic actions of many microorganisms and is an efficient and environmentally benign process for degrading macromolecular organic compounds. We investigated the dynamics of metabolite profiles, bacterial and fungal communities and their interactions during fermentation using cigar leaves from three geographic regions. The results showed that the contents of total sugar, reducing sugar, starch, cellulose, lignin, pectin, polyphenol and protein in cigar tobacco leaves was significantly decreased during fermentation. Notably, the furfural, neophytadiene, pyridine, benzyl alcohol, geranylacetone, 3-hydroxy-2-butanone, N-hexanal, 3-Methyl-1-butanol and 2,3-pentanedione were important features volatile aroma compounds during fermentation. The α-diversity of fungi and bacteria initially increased and then decreased during fermentation. An analysis of variance showed that microbial diversity was influenced by fermentation stages and growing locations, in which the all stages had greater impacts on α- and ß-diversity than all regions. Microbiome profiling had identified several core bacteria including Sphingomonas, Bacillus, Staphylococcus, Pseudomonas, Ralstonia, Massilia and Fibrobacter. Fungal biomarkers included Aspergillus, Penicillium, Fusarium, Cladosporium and Trichomonascus. Interestingly, the molecular ecological networks showed that the core taxa had significant correlations with metabolic enzymes and physicochemical properties; bacteria and fungi jointly participated in the carbohydrate and nitrogen compound degrading and volatile aroma compound chemosynthesis processes during fermentation. These studies provide insights into the coupling of material conversion and microbial community succession during leaf fermentation.

Extraction and characterization of anti-virus anthraquinones from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220.

In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.

Hypomethylation of DRD2 promotes breast cancer through the FLNA-ERK pathway.

We investigated the effect of stem cell marker dopamine receptor D2 (DRD2) on the proliferation of hormone-receptor-negative breast cancer cells. High-throughput DNA methylation sequencing on an 850 K chip was used to pre-screen breast cancer tissues with significant methylation differences. The expression of DRD2 in breast cancer and normal breast tissues, and clinical risk factors, were detected by pyrophosphoric acid validation and immunohistochemistry. In vitro and in vivo experiments verified the possible molecular signaling pathways. DRD2 promoter region was hypomethylated in hormone-receptor-negative breast cancer or with high-risk factors compared to the normal tissues. The proliferation of breast cancer cells was enhanced after DRD2 was upregulated and decreased after DRD2 was downregulated. In vivo experiments found that tumor growth and the expression of antigen KI-67 (Ki67) and the cluster of differentiation 31 (CD31) were improved by the overexpression of DRD2 and inhibited by the down expression of DRD2. In vivo and in vitro experiments demonstrated the phosphorylation of filamin A and extracellular signal-regulated kinase (FLNA-ERK) was influenced by the expression of DRD2, suggesting DRD2 plays a role in the FLNA-ERK signaling pathway. Methylation inhibitors (5-aza-2-deoxycytidine, 5-azadc) partially reversed the inhibitory effect of DRD2 down expression on cell proliferation, migration, and tumor growth in animal models, indicating that inhibition of DRD2 methylation promotes cancer development. This study demonstrated the DRD2 promoter region is hypomethylated in hormone-receptor-negative breast cancer or with high-risk factors. The methylation status of the DRD2 promoter and FLNA-ERK signaling pathway and the DRD2 expression in breast cancer treatment need to be considered.

Rubus chingii Hu relieved the polycystic ovary syndrome with enhanced insulin sensitivity through inhibiting TXNIP/NLRP3 inflammasome signaling.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in gynecology with severe metabolic abnormalities. Therefore, identifying effective treatments and drugs for PCOS is important. We aimed to investigate effect of the traditional Chinese medicine (TCM) Rubus chingii Hu (R. chingii) on ovarian function and insulin resistance (IR) of PCOS rat models, and to explore the underlying mechanisms. METHODS: A PCOS rat model was established by subcutaneous injection of dehydroepiandrosterone (DHEA) solution for 20 days. PCOS rats were randomly divided into a control group (CON), model group (MOD), metformin group (MET), TCM R. chingii group (RCG), and RCG + Ad-TXNIP groups. After 28 days of treatment, the samples were collected for subsequent experiments. RESULTS: R. chingii treatment alleviated hormone imbalance and IR while improving ovarian pathology in the PCOS model. R. chingi inhibited the activation of the thioredoxin-interacting protein (TXNIP)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in the ovarian tissue of PCOS rats. Furthermore, TXNIP overexpression hindered the protective effect of R. chingii intervention in PCOS rats, as evidenced by the increase of homeostasis model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), testosterone (T), C-reactive protein (CRP) levels, and atretic follicles. CONCLUSION: R. chingii intervention improved ovarian polycystic development by suppressing the TXNIP/NLRP3 inflammasome, which may be an effective treatment for PCOS.

Experimental study of EGFR-TKI aumolertinib combined with ionizing radiation in EGFR mutated NSCLC brain metastases tumor.

Aumolertinib is an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), although it has been administered for the treatment of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). However, it is unclear whether aumolertinib combined with ionizing radiation (IR) has potential therapeutic effects in treating brain metastases (BM) tumors from NSCLC. This study explored the anti-tumor effects of aumolertinib combined with IR in epidermal growth factor receptor mutated (EGFRm) NSCLC BM tumors. First, we established a xenograft model of NSCLC BM tumors in BALB/c nude mice and assessed the anti-tumor effects of this combination. Furthermore, we examined the concentrations of aumolertinib in brain tissue and blood using liquid chromatography-mass spectrometry (LC-MS); after that, we used CCK-8, colony formation, flow cytometry assay, and immunofluorescence staining to detect the effects of aumolertinib combined with IR upon PC-9 and NCI-H1975 cells, such as cell proliferation, survival, apoptosis, cycle distribution, the situation of DNA damage, and the expression levels of relevant proteins which were detected via western blotting; finally, we chose a clinical case with which to explore the clinical benefits to the EGFRm NSCLC BM patient after the treatment of the aforementioned combination. The experiments of NSCLC BM tumor animal models demonstrated that the combination enhanced the therapeutic effects and increased the intracranial accumulation of aumolertinib; the combination can inhibit cell proliferation and survival, delay the repair of DNA damage, and increase the rates of cell apoptosis and aumolertinib abrogated G2/M phase arrest, which the IR induced; the clinical study verified that the combination demonstrated better patient benefits. In conclusion, our study demonstrated that combining aumolertinib and IR has promising anti-tumor effects in EGFR-mutant NSCLC and that this combined treatment modality may be employed as a potential therapeutic strategy for EGFR-mutant NSCLC BM patients clinically.

Nitric Oxide-Loaded Bioinspired Lipoprotein Normalizes Tumor Vessels To Improve Intratumor Delivery and Chemotherapy of Albumin-Bound Paclitaxel Nanoparticles.

The disorganized vasculatures in tumors represent a substantial challenge of intratumor nanomedicine delivery to exert the anticancer effects. Herein, we rationally designed a glutathione (GSH)-activated nitric oxide (NO) donor loaded bioinspired lipoprotein system (NO-BLP) to normalize tumor vessels and then promote the delivery efficiency of sequential albumin-bound paclitaxel nanoparticles (PAN) in tumors. NO-BLP exhibited higher tumor accumulation and deeper penetration versus the counterpart liposomal formulation (NO-Lipo) in 4T1 breast cancer tumors, thus producing notable vascular normalization efficacy and causing a 2.33-fold increase of PAN accumulation. The sequential strategy of NO-BLP plus PAN resulted in an 81.03% inhibition of tumor growth in 4T1 tumors, which was better than the NO-BLP monotherapy, PAN monotherapy, and the counterpart NO-Lipo plus PAN treatment. Therefore, the bioinspired lipoprotein of NO-BLP provides an encouraging platform to normalize tumor vessels and promote intratumor delivery of nanomedicines for effective cancer treatment.

Bloodletting Acupuncture at Jing-Well Points Alleviates Myocardial Injury in Acute Altitude Hypoxic Rats by Activating HIF-1α/BNIP3 Signaling-Mediated Mitochondrial Autophagy and Decreasing Oxidative Stress.

OBJECTIVE: To explore the protective effect and possible mechanisms of bloodletting acupuncture at Jing-well points (BAJP) pre-treatment on acute hypobaric hypoxia (AHH)-induced myocardium injury rat. METHODS: Seventy-five rats were randomly divided into 5 groups by a random number table: a control group (n=15), a model group (n=15), a BAJP group (n=15), a BAJP+3-methyladenine (3-MA) group (n=15), and a BANA (bloodletting at nonacupoint; tail bleeding, n=15) group. Except for the control group, the AHH rat model was established in the other groups, and the corresponding treatment methods were adopted. Enzyme-linked immunosorbent assay (ELISA) was used to detect creatine kinase isoenzyme MB (CK-MB) and cardiac troponins I (CTnI) levels in serum and superoxide dismutase (SOD) and malondialdehyde (MDA) levels in myocardial tissue. Hematoxylin-eosin (HE) staining was used to observe myocardial injury, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining was used to observe cell apoptosis. Transmission electron microscopy detection was used to observe mitochondrial damage and autophagosomes in the myocardium. The mitochondrial membrane potential of the myocardium was analyzed with the fluorescent dye JC-1. Mitochondrial respiratory chain complex (complex I, III, and IV) activities and ATPase in the myocardium were detected by mitochondrial respiratory chain complex assay kits. Western blot analysis was used to detect the autophagy index and hypoxia inducible factor-1α (HIF-1α)/Bcl-2 and adenovirus E1B 19k Da-interacting protein 3 (BNIP3) signaling. RESULTS: BAJP reduced myocardial injury and inhibited myocardial cell apoptosis in AHH rats. BAJP pretreatment decreased MDA levels and increased SOD levels in AHH rats (all P<0.01). Moreover, BAJP pretreatment increased the mitochondrial membrane potential (P<0.01), mitochondrial respiratory chain complex (complexes I, III, and IV) activities (P<0.01), and mitochondrial ATPase activity in AHH rats (P<0.05). The results from electron microscopy demonstrated that BAJP pretreatment improved mitochondrial swelling and increased the autophagosome number in the myocardium of AHH rats. In addition, BAJP pretreatment activated the HIF-1α/BNIP3 pathway and autophagy. Finally, the results of using 3-MA to inhibit autophagy in BAJP-treated AHH rats showed that suppression of autophagy attenuated the treatment effects of BAJP in AHH rats, further proving that autophagy constitutes a potential target for BAJP treatment of AHH. CONCLUSION: BAJP is an effective treatment for AHH-induced myocardial injury, and the mechanism might involve increasing HIF-1α/BNIP3 signaling-mediated autophagy and decreasing oxidative stress.

Development of iron-based biochar for enhancing nitrate adsorption: Effects of specific surface area, electrostatic force, and functional groups.

The problem of nitrate contamination in water has attracted widespread attention. Original biochar has a poor adsorption capacity for nitrate adsorption. Iron impregnation and acid protonation (base deprotonation) are common modification methods for biochar. In order to develop iron-mediated biochar containing multi-functional groups for enhancing nitrate adsorption, Fe-BC@H and Fe-BC@OH were prepared using a two-stage development process, including an iron-based carbon pyrolysis followed by acid protonation (or base deprotonation). The pseudo-second-order kinetic and Langmuir models can well describe the adsorption process which is a physicochemical complex monolayer adsorption. The data proved that Fe-BC@H (9.35 mg/g NO3--N) had a stronger adsorption capacity than Fe-BC@OH (2.95 mg/g NO3--N). Surface morphologies, functional groups, and mineral compositions of Fe-BC@H and Fe-BC@OH were analyzed through Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Characterization results showed that acid protonation can further improve the specific surface area (SSA), pore volume, and Zeta potential of Fe-based biochar, providing more adsorption sites for nitrate and enhancing the electrostatic force between nitrate and biochar. However, these effects were suppressed through base deprotonation. In addition, acid protonation can significantly increase the type and number of functional groups of biochar to enhance the chemisorption of nitrate. Such results suggested that the acid protonation can further improve the adsorption capacity of Fe-based biochar for nitrate, while base deprotonation had an inhibitory effect on that of Fe-based biochar. Overall, this study reveals that specific surface area, electrostatic force, and functional groups are crucial effects of the nitrate adsorption on acid/base modified biochar.

Photocatalytic disinfection for point-of-use water treatment using Ti3+ self-doping TiO2 nanoparticle decorated ceramic disk filter.

The challenge from pathogenic infections still threatens the health and life of people in developing areas. An efficient, low-cost, and abundant-resource disinfection method is desired for supplying safe drinking water. This study aims to develop a novel Ti3+ doping TiO2 nanoparticle decorated ceramic disk filter (Ti3+/TiO2@CDF) for point-of-use (POU) disinfection of drinking water. The production of Ti3+/TiO2@CDF was optimized to maximize disinfection efficiency and flow rate. Under optimal conditions, the log reduction value (LRV) could reach up to 7.18 and the flaw rate was 108 mL/h. The influences of environmental factors were also investigated. Natural or slightly alkaline conditions, low turbidity, and low concentration of humic acid were favorable for the disinfection of Ti3+/TiO2@CDF, while co-existing HCO3- ions and diatomic cations (Ca2+ and Mg2+) exhibited the opposite effect. Furthermore, the practicability and stability of Ti3+/TiO2@CDF was demonstrated. Ti3+/TiO2@CDF showed high disinfection efficiency for E. coli and S. aureus under a range of concentrations. Long-term experiment indicated that Ti3+/TiO2@CDF was stable. The underlying disinfection mechanisms were investigated and concluded as the combination of retention, adsorption, and photocatalytic disinfection. The developed Ti3+/TiO2@CDF can provide an effective and reliable disinfection tool for POU water treatment in remote area.

3BDO inhibits the proliferation, epithelial-mesenchymal transition (EMT), and stemness via suppressing survivin in human glioblastoma cells.

Background: Glioblastoma (GBM) is a tumor of the central nervous system with an extremely poor prognosis. Stemness and EMT play important roles in GBM progression. 3-benzyl-5-((2-nitrophenoxy) methyl) dihydrofuran-2(3H)-one (3BDO), an autophagy inhibitor, has been reported to exert anti-cancer activities on lung carcinoma. However, the effects of 3BDO on GBM remain unknown. Therefore, the purpose of this study was to explore the effects of 3BDO on GBM and to investigate the underlying molecular mechanisms. Method: CCK-8 experiments and clone formation assays were conducted to determine the level of cell proliferation. Transwell assay was conducted to examine cell migration and invasion abilities. Western blotting and immunofluorescence staining were used to analyze protein expression levels. A xenograft mouse model was used to evaluate the effect of 3BDO in vivo. Results: We found that 3BDO inhibited U87 and U251 cell proliferation in a dose-dependent manner. Additionally, 3BDO decreased the degree of sphere formation and levels of stemness markers (sox2, nestin, and CD133) in GSCs. 3BDO also inhibited migration and invasion abilities and suppressed EMT markers (N-cadherin, vimentin, and snail) in GBM cells. Moreover, we found that 3BDO downregulated the expression of survivin in both GBM cells (U87, U251) and GSCs. Furthermore, overexpression of survivin decreased the therapeutic effect of 3BDO on EMT, invasion, migration, and proliferation of GBM cells, as well as decreased the stemness of GSCs. Finally, we demonstrated that 3BDO could inhibit tumor growth in a tumor xenograft mouse model constructed using U87 cells. Similar to the in vitro findings, 3BDO decreased the expression of survivin, EMT makers, and the degree of stemness in vivo. Conclusions: Our results demonstrate that 3BDO can repress GBM both in vitro and in vivo via downregulating survivin-mediated stemness and EMT.

Bioinspired Lipoproteins of Furoxans-Oxaliplatin Remodel Physical Barriers in Tumor to Potentiate T-Cell Infiltration.

The infiltration of cytotoxic T lymphocytes (CTLs) in tumors is critically challenged by the intricate intratumor physical barriers, which is emerging as an important issue of anticancer immunotherapy. Herein, a reduction-sensitive nitric oxide donor conjugate of furoxans-oxaliplatin is synthesized and a stroma-cell-accessible bioinspired lipoprotein system (S-LFO) is designed, aiming to facilitate CTL infiltration in tumors for anticancer immunotherapy. S-LFO treatment significantly promotes tumor vessel normalization and eliminates multiple components of tumor stroma, ultimately producing a 2.96-fold, 5.02-fold, and 8.65-fold increase of CD3+ CD8+ T cells, their interferon-γ- and granzyme B-expressing subtypes when comparing to the negative control, and considerably facilitating their trafficking to the cancer cell regions in tumors. Moreover, the combination of S-LFO with an antiprogrammed death ligand-1 produces notable therapeutic benefits of retarded tumor growth and extends survivals in three murine tumor models. Therefore, this study provides an encouraging strategy of remodeling the intratumor physical barriers to potentiate CTL infiltration for anticancer immunotherapy.

Whole Genome Sequencing of Single-Circulating Tumor Cell Ameliorates Unraveling Breast Cancer Heterogeneity.

Objective: Because tumor tissues are most frequently heterogeneous and hard to characterize, the resulting therapeutic strategy could be misled. The most active and invasive tumor cells are circulating tumor cells (CTCs). In this study, we investigated the feasibility of individualized treatment of breast cancer patients based on whole genome sequencing (WGS) of single cell CTC. Methods: Twenty-four CTCs were identified in three breast cancer patients. For each patient, one polyploid CTC was captured, and on which the WGS was performed. WGS was considered due to its sequencing robustness compared to conventional sequencing approaches. Based on the histopathological Her-2 status in tumor tissue and the HER2 gene status in WGS results of CTC, we adjusted treatment strategies and monitored disease progression. Results: Patients ID1 and ID2 are found to be Her-2 positive in primary tumors and HER2 gene amplification in the DNA of CTCs. In-patient ID3, histopathological examination of the primary tumor and liver metastases revealed Her-2 negative, but the WGS analysis of CTC showed HER2 gene amplification. After adjusting treatment by adding Her-2 inhibitors according to the results of CTC sequencing, liver metastases and pleural effusion were significantly reduced two months later, CTC number and ctDNA burden were decreased, and 18-months progression-free survival (PFS) was recorded. In addition, some potential therapeutic targets and mutations in drug-resistant genes were detected. Conclusion: The results of CTC sequencing effectively guided the treatment of a patient with HER2 gene amplification in CTC but with Her-2 negative on tumor tissue. Therefore, CTC sequencing could help resolve the heterogeneity of tumors and provide precision medicine for patients.