A synthetic bacterial consortium improved the phytoremediation efficiency of ryegrass on polymetallic contaminated soil.

Polymetallic contamination of soils caused by mining activities seriously threatens soil fertility, biodiversity and human health. Bioremediation is thought to be of low cost and has minimal environmental risk but its effectiveness needs to be improved. This study aimed to identify the combined effect of plant growth and microbial strains with different functions on the enhancement of bioremediation of polymetallic contaminated soil. The microbiological mechanism of bioremediation was explored by amplicon sequencing and gene prediction. Soil was collected from polymetallic mine wastelands and a non-contaminated site for use in a pot experiment. Remediation efficiency of this method was evaluated by planting ryegrass and applying a mixed bacterial consortium comprising P-solubilizing, N-fixing and SO4-reducing bacteria. The plant-microbe joint remediation method significantly enhanced the above-ground biomass of ryegrass and soil nutrient contents, and at the same time reduced the content of heavy metals in the plant shoots and soil. The application of the composite bacterial inoculum significantly affected the structure of soil bacterial communities and increased the bacterial diversity and complexity, and the stability of co-occurrence networks. The relative abundance of the multifunctional genera to which the strains belonged showed a significant positive correlation with the soil nutrient content. Genera related to carbon (C), nitrogen (N), phosphorus (P), and sulphur (S) cycling and heavy metal resistance showed an up-regulation trend in heavy metal-contaminated soils after the application of the mixed bacterial consortium. Also, bacterial strains with specific functions in the mixed consortium regulated the expression of genes involved in soil nutrient cycling, and thus assisted in making the soil self-sustainable after remediation. These results suggested that the remediation of heavy metal-contaminated soil needs to give priority to the use of multifunctional bacterial agents.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical. METHODS: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety. FINDINGS: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3). CONCLUSIONS: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation. FUNDING: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).

Two doses of fosaprepitant included prophylactic treatment for the three-day cisplatin-based chemotherapy induced nausea and vomiting.

PURPOSE: Neurokinin 1 receptor antagonists included prophylactic treatment was recommended for patients who receive one-day cisplatin chemotherapy. It is unclear whether the prolonged administration of fosaprepitant is effective for three-day cisplatin-based chemotherapy induced nausea and vomiting (CINV). We aim to explore the prophylactic antiemetic efficacy and safety of two doses of fosaprepitant included regimen in the patients receiving multiple-day cisplatin chemotherapy. METHODS: This randomized, parallel-group, open-labelled study was conducted in nine hospitals between February 2021 and February 2023. Patients diagnosed as lung cancer and chemotherapy naive were screened. Eligible participants were scheduled to be treated with highly emetogenic chemotherapy regimen which including three days of cisplatin. Then they were randomly divided into the experimental group (two doses of fosaprepitant, Group 2DF) and the control group (one dose of fosaprepitant, Group C). The primary endpoints included the safety and the average none CINV days (NCDs). This study was registered on the website of chictr.org.cn, number ChiCTR2100042665. RESULTS: Overall, 204 participants were randomly assigned, and 198 patients were analyzed. No statistical difference in adverse events was found between the two groups. All treatment-related adverse effects for fosaprepitant observed were of grade 1-2. The average NCDs of Group 2DF was significantly more than Group C (18.21 ± 3.40 days vs 16.14 ± 5.20 days, P = 0.001). Furthermore, the better life function score was achieved in Group 2DF according to FLIE questionnaire. CONCLUSION: The administration of two-dose fosaprepitant was safe and more effective than one dose in protecting patients from CINV induced by three-day cisplatin included chemotherapy.

Undescribed steroidal alkaloids from the bulbs of Fritillaria ussuriensis Maxim and their anti-inflammatory activities.

In total, 16 undescribed steroidal alkaloids (1-16), along with nine known ones (17-25), were isolated from the bulbs of Fritillaria ussuriensis Maxim. Among the undescribed compounds mentioned, compounds 1-6, 8 bearing an 16ß-hydroxy substituent, as well as compounds 13 and 14 exhibited an unusual seven-membered skeleton. Their structures were established based on extensive spectroscopic analyses, including HRESIMS and NMR (1D and 2D), and comparison with the data reported in the literature. Furthermore, all the compounds were evaluated for their anti-inflammatory effect on the NO production of LPS-stimulated RAW264.7 cells. Compounds 1, 4, 11, 15, 22 and 24 could significantly inhibit NO production with IC50 values below 10 µM.

Immunotherapy for patients with advanced non-small cell lung cancer harboring oncogenic driver alterations other than EGFR: a multicenter real-world analysis.

Background: The administration of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) with oncogenic driver alterations other than epidermal growth factor receptor (EGFR) aroused a heated discussion. We thus aimed to evaluate ICI treatment in these patients in real-world routine clinical practice. Methods: A multicenter, retrospective study was conducted for NSCLC patients with at least one gene alteration (KRAS, HER2, BRAF, MET, RET, ALK, ROS1) receiving ICI monotherapy or combination treatment. The data regarding clinicopathologic characteristics, clinical efficacy, and safety were investigated. Results: A total of 216 patients were included, the median age was 60 years, 72.7% of patients were male, and 46.8% had a smoking history. The molecular alterations involved KRAS (n=95), HER2 (n=42), BRAF (n=22), MET (n=21), RET (n=14), ALK (n=14), and ROS1 (n=8); 56.5% of patients received immunotherapy in the first-line, and the rest 43.5% were treated as a second-line and above. For the entire cohort who received immunotherapy-based regimens in the first-line, the median progression-free survival (PFS) was 7.5 months and the median overall survival (OS) was 24.8 months. For the entire cohort who received immunotherapy-based regimens in the second-line and above, the median PFS was 4.7 months and median OS was 17.1 months. KRAS mutated NSCLC treated with immunotherapy-based regimens in the first-line setting had a median PFS and OS were 7.8 and 26.1 months, respectively. Moreover, the median PFS and OS of immunotherapy-based regimens for KRAS-mutant NSCLC that progressed after chemotherapy were 5.9 and 17.1 months. Programmed death ligand 1 (PD-L1) expression level was not consistently associated with response to immunotherapy across different gene alteration subsets. In the KRAS group, PD-L1 positivity [tumor proportion score (TPS) ≥1%] was associated with better PFS and OS according to the multivariate Cox analysis. No statistically significant association was found for smoking status, age, or gender with clinical efficacy in any gene group analyses. Conclusions: KRAS-mutant NSCLC could obtain clinical benefits from ICIs either for treatment-naive patients or those who have experienced progression after chemotherapy, and PD-L1 positive expression (TPS >1%) may be a potential positive predictor. For NSCLC with ALK, RET and ROS1 rearrangement, MET exon 14 skipping mutation, or BRAF V600E mutation, effectiveness of single or combined ICI therapy remains limited, therefore, targeted therapies should be considered prior to immunotherapy regimens. Future studies should address the investigation of better predictive biomarkers for immunotherapy response in oncogene-driven NSCLC.

[Retracted] MicroRNA­19b promotes the migration and invasion of ovarian cancer cells by inhibiting the PTEN/AKT signaling pathway.

[This retracts the article DOI: 10.3892/ol.2018.8695.].

[Source Apportionment of Morphine in Wastewater].

It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are complex, and distinguishing the contribution of different sources has become a key issue. A total of 262 influent samples from 61 representative wastewater treatment plants in a typical city were collected from October 2022 to March 2023. The concentrations of morphine, codeine, thebaine, papaverine, noscapine, and monoacetylmorphine were analyzed in wastewater and poppy straws. Combined with the proportion of alkaloids in poppy straws, the source analysis of alkaloids in wastewater was analyzed using the ratio method and positive matrix factorization model (PMF). Only five alkaloids were detected in wastewater, and monoacetylmorphine, a metabolite of heroin, was not detected. The concentrations of morphine and codeine were significantly higher than those of noscapine, papaverine, and thebaine. By constructing the ratios of codeine/(morphine + codeine) and noscapine/(noscapine + codeine), the source of poppy straw could be qualitatively distinguished. The PMF results showed that three sources of morphine for medical use, poppy straw, and codeine contributed 44.9%, 43.7%, and 9.4%, respectively. The different sources varied in these months due to the COVID-19 and influenza A outbreaks, in which the use of drugs containing poppy straws and codeine was the main source, whereas the use of morphine analgesics remained relatively stable. Inventory analysis further demonstrated the reliability of the source contributions from the PMF model, and morphine was not abused in this city.

Development of a novel DGT passive sampler for measuring polycyclic aromatic hydrocarbons in aquatic systems.

Polycyclic aromatic hydrocarbons (PAHs) are priority pollutants and need to be measured reliably in waters and other media, to understand their sources, fate, behaviour and to meet regulatory monitoring requirements. Conventional water sampling requires large water volumes, time-consuming pre-concentration and clean-up and is prone to analyte loss or contamination. Here, for the first time, we developed and validated a novel diffusive gradients in thin-films (DGT) passive sampler for PAHs. Based on the well-known DGT principles, the sampler pre-concentrates PAHs with typical deployment times of days/weeks, with minimal sample handling. For the first time, DGT holding devices made of metal and suitable for sampling hydrophobic organic compounds were designed and tested. They minimize sorption and sampling lag times. Following tests on different binding layer resins, a MIP-DGT was preferred - the first time applying MIP for PAHs. It samples PAHs independent of pH (3.9 -8.1), ionic strength (0.01 -0.5 M) and dissolved organic matter < 20 mg L-1, making it suitable for applications across a wide range of environments. Field trials in river water and wastewater demonstrated that DGT is a convenient and reliable tool for monitoring labile PAHs, readily achieving quantitative detection of environmental levels (sub-ng and ng/L range) when coupled with conventional GC-MS or HPLC. ENVIRONMENTAL IMPLICATIONS: PAHs are carcinogenic and genotoxic compounds. They are environmentally ubiquitous and must be monitored in waters and other media. This study successfully developed a new DGT passive sampler for reliable in situ time-integrated measurements of PAHs in waters at the ng/L level. This is the first time to use passive samplers for accurate measurements of hydrophobic organic contaminants in aquatic systems without calibration, a big step forward in monitoring PAHs. The application of this new sampler will enhance our understanding of the sources, fate, behavior and ecotoxicology of PAHs, enabling improved environmental risk assessment and management of these compounds.

Myosteatosis is associated with coronary artery calcification in patients with type 2 diabetes.

BACKGROUND: Myosteatosis, rather than low muscle mass, is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus (T2DM). Myosteatosis may lead to a series of metabolic dysfunctions, such as insulin resistance, systematic inflammation, and oxidative stress, and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis. AIM: To investigate the association between myosteatosis and coronary artery calcification (CAC) in patients with T2DM. METHODS: Patients with T2DM, who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography (CT) scans, were included. The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level. The CAC score was determined from thoracic CT images using the Agatston scoring method. Myosteatosis was diagnosed according to Martin's criteria. Severe CAC (SCAC) was defined when the CAC score exceeded 300. Logistic regression and decision tree analyses were performed. RESULTS: A total of 652 patients with T2DM were enrolled. Among them, 167 (25.6%) patients had SCAC. Logistic regression analysis demonstrated that myosteatosis, age, duration of diabetes, cigarette smoking, and alcohol consumption were independent risk factors of SCAC. Myosteatosis was significantly associated with an increased risk of SCAC (OR = 2.381, P = 0.003). The association between myosteatosis and SCAC was significant in the younger patients (OR = 2.672, 95%CI: 1.477-4.834, P = 0.002), but not the older patients (OR = 1.456, 95%CI: 0.863-2.455, P = 0.188), and was more prominent in the population with lower risks of atherosclerosis. The decision tree analyses prioritized older age as the primary variable for SCAC. In older patients, cigarette smoking was the main contributing factor for SCAC, while in younger patients, it was myosteatosis. CONCLUSION: Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM, especially in the population with younger ages and fewer traditional risk factors.

Functional investigation of a novel ANKRD11 frameshift variant identified in a Chinese family with KBG syndrome.

KBG syndrome is a rare autosomal dominant condition characterized by multisystem developmental disorder, primarily caused by loss-of-function variants in ankyrin repeat domain-containing protein 11 (ANKRD11). Approximately 80 % of ANKRD11 variants associated with KBG syndrome, are frameshift and nonsense variants. Current insight into the pathogenesis of KBG syndrome resulting from ANKRD11 truncating variants remains limited. Here, we presented two members from a non-consanguineous Chinese pedigree both exhibiting characteristics fitting the KBG syndrome-associated phenotypic spectrum. Whole-exome sequencing identified a novel heterozygous frameshift variant in ANKRD11 (NM_013275.6, c.2280_2281delGT, p.Y761Qfs*20) in the proband. Sanger sequencing confirmed that the variant was inherited from her mother and co-segregated with KBG syndrome phenotype. In vitro functional assays revealed that the frameshift variant escaped nonsense-mediated mRNA decay, and resulting in a truncated protein with significantly increased expression levels compared to full-length ANKRD11. Immunofluorescence results demonstrated that truncated protein was predominantly expressed in the nucleus of HEK293 cells, while wild-type ANKRD11 was equally distributed in both the nucleus and cytoplasm. Moreover, the truncated protein significantly reduced CDKN1A/P21-promoter luciferase activity in comparison to wild-type ANKRD11 protein, as well as a remarkably decrease in the endogenous CDKN1A/P21 mRNA level in HEK293 cells. These findings suggest a loss of transcriptional activation function and potentially a dominant-negative mechanism. Overall, our study expands the mutational spectrum of ANKRD11 gene and provides new insights into the pathogenic mechanism of KBG syndrome caused by ANKRD11 truncating variants.

Correction: A Y1 receptor ligand synergized with a P-glycoprotein inhibitor improves the therapeutic efficacy of multidrug resistant breast cancer.

Correction for 'A Y1 receptor ligand synergized with a P-glycoprotein inhibitor improves the therapeutic efficacy of multidrug resistant breast cancer' by Yinjie Wang et al., Biomater. Sci., 2019, 7, 4748-4757, https://doi.org/10.1039/C9BM00337A.

Identification and functional analysis of first heterozygous frameshift mutation in the GHRH gene in a Chinese boy with isolated growth hormone deficiency.

BACKGROUND: Isolated growth hormone deficiency (IGHD) is a rare genetically heterogeneous disorder caused primarily by mutations in GH1 and GH releasing hormone receptor (GHRHR). The aim of this study was to identify the molecular etiology of a Chinese boy with IGHD. METHODS: Whole-exome sequencing, sanger sequencing and bioinformatic analysis were performed to screen for candidate mutations. The impacts of candidate mutation on gene expression, intracellular localization and protein function were further evaluated by in vitro assays. RESULTS: A novel heterozygous frameshift mutation in the GHRH gene (c.91dupC, p.R31Pfs*98) was identified in a Chinese boy clinically diagnosed as having IGHD. The mutation was absent in multiple public databases, and considered as deleterious using in silico prediction, conservative analysis and three-dimensional homology modeling. Furthermore, mRNA and protein expression levels of mutant GHRH were significantly increased than wild-type GHRH (p < 0.05). Moreover, mutant GHRH showed an aberrant accumulation within the cytoplasm, and obviously reduced ability to stimulate GH secretion and cAMP accumulation in human GHRHR-expressing pituitary GH3 cells compared to wild-type GHRH (p < 0.05). CONCLUSION: Our study discovered the first loss-of function mutation of GHRH in a Chinese boy with IGHD and provided new insights on IGHD pathogenesis caused by GHRH haploinsufficiency.

Development and validation of an in situ high-resolution technique for measuring antibiotics in sediments.

Important biogeochemical processes occur in sediments at fine scales. Sampling techniques capable of yielding information with high resolution are therefore needed to investigate chemical distributions and fluxes and to elucidate key processes affecting chemical fates. In this study, a high-resolution diffusive gradients in thin-films (DGT) technique was systematically developed and tested in a controlled sediment system to measure organic contaminants, antibiotics, for the first time. The DGT probe was used to resolve compound distributions at the mm scale. It also reflected the fluxes from the sediment pore-water and remobilization from the solid phase, providing more dynamic information. Through the fine scale detection, a reduction of re-supply was observed over time, which was concentration and location dependent. Compared to the Rhizon sampling method, antibiotic concentrations obtained by DGT probes were less than the pore-water concentrations, as DGT measures the labile fraction of the compounds. The DGT probe was also tested on an intact sediment core sampled from a lake in China and used to measure the distribution of labile antibiotics with depth in the core at the mm scale. ENVIRONMENTAL IMPLICATION: The abuse of antibiotics and widespread of their residues influences the ecosystem, induces the generation of super-bacteria, and finally poses threat to human health. Sediments adsorbs pollutants from the aquatic environment, while may also release them back to the environment. We systematically developed DGT probe approach for measuring antibiotics in sediment in situ in high resolving power, it provides information at fine scale to help us investigate biogeochemical processes take place in sediment and sediment-water interface.

Molecular diagnosis is an important indicator for response to growth hormone therapy in children with short stature.

BACKGROUND: Significant differences have been observed in the efficacy of recombinant human growth hormone (rhGH) treatment for short children. The present study aimed to identify the genetic etiology of short stature and to assess the role of molecular diagnosis in predicting responses to rhGH treatment. METHODS: A total of 407 short children were included in the present study, 226 of whom received rhGH treatment. Whole-exome sequencing (WES) was conducted on short children to identify the underlying genetic etiology. Correlations between molecular diagnosis and the efficacy of rhGH treatment were examined. RESULTS: Pathogenic or likely pathogenic mutations were identified in 86 of the 407 patients (21.1%), including 36 (41.9%) novel variants. Among the multiple pathways affecting short stature, genes involved in fundamental cellular processes (38.7%) play a larger role, especially the RAS-MAPK pathway. In general, patients without pathogenic mutations responded better to rhGH than those with mutations. Furthermore, patients with hormone signaling pathway mutations had a better response to rhGH, while those with paracrine factor mutations had a worse response to rhGH. CONCLUSIONS: This study highlights the utility of WES in identifying genetic etiology in children with short stature. Identifying likely causal mutations is an important factor in predicting rhGH response.

Effect of short neuropeptide F signaling on larval feeding in Mythimna separata.

Mythimna separata is a notorious phytophagous pest which poses serious threats to cereal crops owing to the gluttony of the larvae. Because short neuropeptide F (sNPF) and its receptor sNPFR are involved in a diversity of physiological functions, especially in functions related to feeding in insects, it is a molecular target for pest control. Herein, an sNPF and 2 sNPFRs were identified and cloned from M. separata. Bioinformatics analysis revealed that the sNPF and its receptors had a highly conserved RLRFamide C-terminus and 7 transmembrane domains, respectively. The sNPF and its receptor genes were distributed across larval periods and tissues, but 2 receptors had distinct expression patterns. The starvation-induced assay elucidated that sNPF and sNPFR expression levels were downregulated under food deprivation and recovered with subsequent re-feeding. RNA interference knockdown of sNPF, sNPFR1, and sNPFR2 by injection of double-stranded RNA into larvae not only suppressed food consumption and increased body size and weight, but also led to decrease of glycogen and total lipid contents, and increase of trehalose compared with double-stranded green fluorescent protein injection. Furthermore, molecular docking was performed on the interaction mode between sNPFR protein and its ligand sNPF based on the 3-dimensional models constructed by AlphaFold; the results indicated that both receptors were presumably activated by the mature peptide sNPF-2. These results revealed that sNPF signaling played a considerably vital role in the feeding regulation of M. separata and represents a potential control target for this pest.

Letrozole combined with rhGH treatment increases the adult height of short pubertal boys.

OBJECTIVES: This study was performed to investigate the effectiveness of the combination of letrozole and recombinant human growth hormone (rhGH) to improve the predicted adult height (PAH) and final adult height (FAH) of Chinese short pubertal boys. METHODS: In total, 171 Chinese short pubertal boys were recruited for this study. 96 of them received letrozole (2.5 mg/d) combined with rhGH (33.3-66.6 µg/kg.d), and the others received rhGH alone. Follow-up visits were conducted at 1, 3, 6, 9, and 12 months or regularly after the first treatment. During each visit, plasma samples were collected for clinical tests and biomedical analyses, all of which were performed according to standard protocols. This study was registered at www.chictr.org.cn under ID number ChiCTR1900026142. RESULTS: After receiving treatment for at least 3 months, 68 boys (91 %) in the rhGH therapy group and 90 (94 %) in the letrozole combined with rhGH (letrozole+rhGH) therapy group achieved an increase in PAH, with the latter treatment leading to a more effective slowing of bone age (BA) advancement. Moreover, the increased PAH showed a significant positive correlation with treatment time in both groups, and letrozole+rhGH increased the PAH to a greater degree than rhGH alone (p=0.0023). And letrozole+rhGH not only slowed the increase in BA more efficiently than rhGH therapy alone (p=0.0025), but also achieved a higher FAH (p=0.0078). CONCLUSIONS: Letrozole combined with rhGH treatment is a promising therapy to increase the PAH and FAH of Chinese short pubertal boys.

A D-Y Shaped Neuropeptide Y Mimetic Peptide-Dye Self-Assembly with Maximal Emission Beyond 1300 nm and Glioma Mitochondrial Activity Modulation.

Neuropeptide Y (NPY), as one of the most abundant neuropeptides known, is widely distributed in the central and peripheral nervous system. However, most of the reported NPY-mimetic peptides are hard to cross the blood-brain barrier, target glioma mitochondria, and achieve self-assembly nanostructure in situ. Here, based on the α-helix structure of the novel chiral NPY-mimetic peptides D/LNPY(14), a Y-shaped peptide is designed with the sequences that can be recognized by enterokinase and achieved nanofibers conversion in glioma cell mitochondria. Coupling the Y-shaped NPY-mimetic peptide with the NIR-II fluorophore IR1048, a red-shifting of the fluorescence spectrum beyond 1300 nm is achieved through self-assembly. After the self-assembly in glioma mitochondria, the formed nanofibers can promote intracellular mitochondrial ROS production and extend the NIR-II fluorescence imaging time to at least 7 days in vivo. This work for the first time endows the self-assembly of α-helical-based chiral NPY-mimetic peptides, providing a novel strategy for glioma subcellular regulation enhanced antitumor treatment guided by NIR-II fluorescence imaging.

[Research Progress of Iron Metabolism in Disease Progression and Drug Resistance of Multiple Myeloma--Review].

Iron metabolism is involved in the development and drug resistance of many malignancies, including multiple myeloma (MM). Based on recent studies on iron metabolism and MM, this paper reviews the relationship between iron metabolism and disease process of MM in terms of iron overload leading to ferroptosis in MM cells, the role of iron deficiency in oxidative respiration and proliferation of MM cells, and the interaction between ferroptosis and autophagy in the disease process. The mechanisms by which iron metabolism-related substances lead to MM cells' resistance to proteasome inhibitors (PI) through inducing redox imbalance and M2 macrophage polarization are also briefly described, aiming to provide a theoretical basis for the application of iron metabolism-related drugs to the clinical treatment of MM patients.

Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy.

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Surveillance of COVID-19 and influenza A(H1N1) prevalence in China via medicine-based wastewater biomarkers.

The simultaneous monitoring of individual or multiple diseases can be achieved by selecting therapeutic medicines used to treat the primary symptoms of the condition as biomarkers in wastewater. This study proposes a novel approach to monitor the prevalence of COVID-19 and influenza A (H1N1) by selecting nine medicines to serve as biomarkers, including three antipyretics, three antivirals, and three cough suppressants. To verify our approach, wastewater samples were collected from seventeen urban and five rural wastewater treatment plants (WWTPs) in a Chinese city over a period of one year. The use of antipyretics increased notably during the COVID-19 pandemic, while the consumption of antivirals for influenza A (H1N1) rose in the post-COVID-19 pandemic period, indicating a minor spike in the occurrence of influenza A (H1N1) after the COVID-19 pandemic. Fever is a significant symptom of COVID-19 and can serve as a reliable indicator of disease prevalence. Our research found that the prevalence of COVID-19 in urban areas was significantly higher (at 78.5 %, 95 % CI: 73.4 % - 83.9 %) than in rural areas (with a prevalence of 48.1 %, 95 % CI: 42.4 % - 53.8 %). The prevalence of COVID-19 in urban areas in this study was consistent with the data reported by the Chinese center for Disease Control and Prevention (82.4 %). Continuous monitoring of WWTPs in urban areas with fluctuating populations and complex demographics can provide early disease warning. Our results demonstrate the feasibility of evaluating community disease prevalence by selecting major therapeutic medicines as biomarkers in wastewater.