Seasonal impact of constructed wetlands on nitrogen and phosphorus in sediments of flood control lakes with pollution assessment.

The primary drivers of eutrophication in lakes following the reduction of external nutrient inputs are the release of N and P from sediments. Constructed wetlands play a pivotal role in ameliorating N, P, and other biogenic element levels. However, the presence of large vegetation in these wetlands also substantially contributes to nutrient accumulation in sediments, a phenomenon influenced by seasonal variations. In this study, a typical constructed wetland was selected as the research site. The research aimed to analyze the forms of N and P in sediments during both summer and winter. Simultaneously, a comprehensive pollution assessment and analysis were conducted within the study area. The findings indicate that elevated summer temperatures, together with the presence of wetland vegetation, promote the release of N through the nitrification process. Additionally, seasonal variations exert a significant impact on the distribution of P storage. Furthermore, the role of constructed wetlands in the absorption and release of N and P is primarily controlled by the influence of organic matter on nitrate-nitrogen, nitrite-nitrogen, and available phosphorus, and is also subject to seasonal fluctuations. In summary, under the comprehensive influence of constructed wetlands, vegetation types, and seasons, sediments within the lake generally exhibit a state of mild or moderate pollution. Therefore, targeted measures should be adopted to optimally adjust vegetation types, and human intervention is necessary, involving timely sediment harvesting during the summer to reduce N and P loads, and enhancing sediment adsorption and retention capacity for N and P during the winter.

Retinoblastoma-associated protein is important for TRIM24-mediated activation of the mTOR signaling pathway through DUSP2 action in prostate cancer.

RB transcriptional corepressor 1 (RB) deletion is the most important genomic factor associated with the prognosis of castration-resistant prostate cancer (CRPC) patients receiving androgen receptor (AR) signaling inhibitor therapy. Loss of RB could support prostate cancer cell growth in a hormone-independent manner, but the underlying mechanism by which RB regulates tumor progression extends far beyond the cell cycle pathway. A previous study indicated that RB inactivates AKT signaling but has no effect on mTOR signaling in cancer cells. Here, we found that the S249/T252 site in RB is key to regulating the transcriptional activity of the tumor-promoting factor TRIM24 in CRPC, as identified through FXXXV mapping. The RB/TRIM24 complex functions through DUSP2, which serves as an intermediate bridge, to activate the mTOR pathway and promote prostate cancer progression. Accordingly, we designed RB-linker-proteolysis-targeting chimera (PROTAC) molecules, which decreased TRIM24 protein levels and inactivated the mTOR signaling pathway, thereby inhibiting prostate cancer. Therefore, this study not only elucidates the novel function of RB but also provides a theoretical basis for the development of new drugs for treating prostate cancer.

Spaced Double Hydrogen Bonding in an Imidazole Poly Ionic Liquid Composite for Highly Efficient and Selective Photocatalytic Air Reductive H2O2 Synthesis.

Photocatalytic oxygen reductive H2O2 production is a promising approach to alternative industrial anthraquinone processes while suffering from the requirement of pure O2 feedstock for practical application. Herein, we report a spaced double hydrogen bond (IC-H-bond) through multi-component Radziszewski reaction in an imidazole poly-ionic-liquid composite (SI-PIL-TiO2) and levofloxacin hydrochloride (LEV) electron donor for highly efficient and selective photocatalytic air reductive H2O2 production. It is found that the IC-H-bond formed by spaced imino (-NH-) group of SI-PIL-TiO2 and carbonyl (-C=O) group of LEV can switch the imidazole active sites characteristic from a covered state to a fully exposed one to shield the strong adsorption of electron donor and N2 in the air, and propel an intenser positive potential and more efficient orbitals binding patterns of SI-PIL-TiO2 surface to establish competitive active sites for selectivity O2 chemisorption. Moreover, the high electron enrichment of imidazole as an active site for the 2e- oxygen reduction ensures the rapid reduction of O2. Therefore, the IC-H-bond enables a total O2 utilization and conversion efficiency of 94.8 % from direct photocatalytic air reduction, achieving a H2O2 production rate of 1518 µmol/g/h that is 16 and 23 times compared to poly-ionic-liquid composite without spaced imino groups (PIL-TiO2) and TiO2, respectively.

Advanced function, design and application of skin substitutes for skin regeneration.

The development of skin substitutes aims to replace, mimic, or improve the functions of human skin, regenerate damaged skin tissue, and replace or enhance skin function. This includes artificial skin, scaffolds or devices designed for treatment, imitation, or improvement of skin function in wounds and injuries. Therefore, tremendous efforts have been made to develop functional skin substitutes. However, there is still few reports systematically discuss the relationship between the advanced function and design requirements. In this paper, we review the classification, functions, and design requirements of artificial skin or skin substitutes. Different manufacturing strategies for skin substitutes such as hydrogels, 3D/4D printing, electrospinning, microfluidics are summarized. This review also introduces currently available skin substitutes in clinical trials and on the market and the related regulatory requirements. Finally, the prospects and challenges of skin substitutes in the field of tissue engineering are discussed.

Clinical advances in TNC delivery vectors and their conjugate agents.

Tenascin C (TNC), a glycoprotein that is abundant in the tumor extracellular matrix (ECM), is strongly overexpressed in tumor tissues but virtually undetectable in most normal tissues. Many TNC antibodies, peptides, aptamers, and nanobodies have been investigated as delivery vectors, including 20A1, α-A2, α-A3, α-IIIB, α-D, BC-2, BC-4 BC-8, 81C6, ch81C6, F16, FHK, Ft, Ft-NP, G11, G11-iRGD, GBI-10, 19H12, J1/TN1, J1/TN2, J1/TN3, J1/TN4, J1/TN5, NJT3, NJT4, NJT6, P12, PL1, PL3, R6N, SMART, ST2146, ST2485, TN11, TN12, TNFnA1A2-Fc, TNfnA1D-Fc, TNfnBD-Fc, TNFnCD-Fc, TNfnD6-Fc, TNfn78-Fc, TTA1, TTA1.1, and TTA1.2. In particular, BC-2, BC-4, 81C6, ch81C6, F16, FHK, G11, PL1, PL3, R6N, ST2146, TN11, and TN12 have been tested in human tissues. G11-iRGD and simultaneous multiple aptamers and arginine-glycine-aspartic acid (RGD) targeting (SMART) may be assessed in clinical trials because G11, iRGD and AS1411 (SMART components) are already in clinical trials. Many TNC-conjugate agents, including antibody-drug conjugates (ADCs), antibody fragment-drug conjugates (FDCs), immune-stimulating antibody conjugates (ISACs), and radionuclide-drug conjugates (RDCs), have been investigated in preclinical and clinical trials. RDCs investigated in clinical trials include 111In-DTPA-BC-2, 131I-BC-2, 131I-BC-4, 90Y-BC4, 131I81C6, 131I-ch81C6, 211At-ch81C6, F16124I, 131I-tenatumomab, ST2146biot, FDC 131I-F16S1PF(ab')2, and ISAC F16IL2. ADCs (including FHK-SSL-Nav, FHK-NB-DOX, Ft-NP-PTX, and F16*-MMAE) and ISACs (IL12-R6N and 125I-G11-IL2) may enter clinical trials because they contain components of marketed treatments or agents that were investigated in previous clinical studies. This comprehensive review presents historical perspectives on clinical advances in TNC-conjugate agents to provide timely information to facilitate tumor-targeting drug development using TNC.

The regulatory effect of growth differentiation factor 11 on different cells.

Growth differentiation factor 11 (GDF11) is one of the important factors in the pathophysiological process of animals. It is widely expressed in many tissues and organs of animals, showing its wide biological activity and potential application value. Previous research has demonstrated that GDF11 has a therapeutic effect on various diseases, such as anti-myocardial aging and anti-tumor. This has not only sparked intense interest and enthusiasm among academics but also spurred some for-profit businesses to attempt to develop GDF11 as a medication for regenerative medicine or anti-aging application. Currently, Sotatercept, a GDF11 antibody drug, is in the marketing application stage, and HS-235 and rGDF11 are in the preclinical research stage. Therefore, we believe that figuring out which cells GDF11 acts on and its current problems should be an important issue in the scientific and commercial communities. Only through extensive, comprehensive research and discussion can we better understand the role and potential of GDF11, while avoiding unnecessary risks and misinformation. In this review, we aimed to summarize the role of GDF11 in different cells and its current controversies and challenges, providing an important reference for us to deeply understand the function of GDF11 and formulate more effective treatment strategies in the future.

A novel nanobody-based HER2-targeting antibody exhibits potent synergistic antitumor efficacy in trastuzumab-resistant cancer cells.

Human epithelial growth factor receptor-2 (HER2) plays an oncogenic role in numerous tumors, including breast, gastric, and various other solid tumors. While anti-HER2 therapies are approved for the treatment of HER2-positive tumors, a necessity persists for creating novel HER2-targeted agents to resolve therapeutic resistance. Utilizing a synthetic nanobody library and affinity maturation, our study identified four anti-HER2 nanobodies that exhibited high affinity and specificity. These nanobodies recognized three distinct epitopes of HER2-ECD. Additionally, we constructed VHH-Fc and discovered that they facilitated superior internalization and showed moderate growth inhibition. Compared to the combination of trastuzumab and pertuzumab, the VHH-Fc combos or their combination with trastuzumab demonstrated greater or comparable antitumor activity in both ligand-independent and ligand-driven tumors. Most remarkably, A9B5-Fc, which targeted domain I of HER2-ECD, displayed significantly enhanced trastuzumab-synergistic antitumor efficacy compared to pertuzumab under trastuzumab-resistant conditions. Our findings offer anti-HER2 nanobodies with high affinity and non-overlapping epitope recognition. The novel nanobody-based HER2-targeted antibody, A9B5-Fc, binding to HER2-ECD I, mediates promising receptor internalization. It possesses the potential to serve as a potent synergistic partner with trastuzumab, contributing to overcoming acquired resistance.

Photothermal antibacterial materials to promote wound healing.

Wound healing is a crucial process that restores the integrity and function of the skin and other tissues after injury. However, external factors, such as infection and inflammation, can impair wound healing and cause severe tissue damage. Therefore, developing new drugs or methods to promote wound healing is of great significance. Photothermal therapy (PTT) is a promising technique that uses photothermal agents (PTAs) to convert near-infrared radiation into heat, which can eliminate bacteria and stimulate tissue regeneration. PTT has the advantages of high efficiency, controllability, and low drug resistance. Hence, nanomaterial-based PTT and its related strategies have been widely explored for wound healing applications. However, a comprehensive review of PTT-related strategies for wound healing is still lacking. In this review, we introduce the physiological mechanisms and influencing factors of wound healing, and summarize the types of PTAs commonly used for wound healing. Then, we discuss the strategies for designing nanocomposites for multimodal combination treatment of wounds. Moreover, we review methods to improve the therapeutic efficacy of PTT for wound healing, such as selecting the appropriate wound dressing form, controlling drug release, and changing the infrared irradiation window. Finally, we address the challenges of PTT in wound healing and suggest future directions.

Multi-material electrospinning: from methods to biomedical applications.

Electrospinning as a versatile, simple, and cost-effective method to engineer a variety of micro or nanofibrous materials, has contributed to significant developments in the biomedical field. However, the traditional electrospinning of single material only can produce homogeneous fibrous assemblies with limited functional properties, which oftentimes fails to meet the ever-increasing requirements of biomedical applications. Thus, multi-material electrospinning referring to engineering two or more kinds of materials, has been recently developed to enable the fabrication of diversified complex fibrous structures with advanced performance for greatly promoting biomedical development. This review firstly gives an overview of multi-material electrospinning modalities, with a highlight on their features and accessibility for constructing different complex fibrous structures. A perspective of how multi-material electrospinning opens up new opportunities for specific biomedical applications, i.e., tissue engineering and drug delivery, is also offered.

MRI is more valuable than CT in the diagnosis of cervical cancer.

OBJECTIVE: To analyze the diagnostic values of CT and MRI for cervical cancer. METHOD: The clinical data of 83 patients with cervical cancer and 16 patients with cervicitis admitted to Zhejiang Putuo Hospital from January 2017 to December 2021 were retrospectively analyzed. Among them, 18 patients receiving CT examination were categorized as the CT group, and the remaining 81 patients with MRI examination were the MRI group. In total, 83 patients were finally diagnosed with cervical cancer through pathologic examination. The diagnostic values of CT and MRI for cervical cancer staging and pathologic features were analyzed. RESULTS: Compared to CT, the sensitivity and accuracy of MRI in diagnosing cervical cancer were higher (P<0.05), as was its detection rate in the diagnosis of stage I and II (P<0.05), but the difference in the detection rate of stage III was not statistically significant. In addition, among the 83 cases of cervical cancer, it was confirmed by surgical and pathological examination that 41 cases experienced parametrial invasion, 65 had interstitial invasion, and 39 had lymph node metastasis. The detection rate of MRI in the diagnosis of interstitial and parametrial invasion was also markedly higher than that of CT (P<0.05), but the difference in the lymph node metastasis detection was not significant. CONCLUSION: MRI can clearly display the structure of various layers of the cervix and its lesions. It is more accurate in clinical diagnosis, staging, and evaluation of pathologic features of cervical cancer compared to CT, and is available on a more reliable basis for diagnosis and treatment.

Alleviation of metal stress in rape seedlings (Brassica napus L.) using the antimony-resistant plant growth-promoting rhizobacteria Cupriavidus sp. S-8-2.

This study investigated an effective strategy for remediating antimony (Sb)-contaminated soil using the bacterial strain screened from Sb-contaminated fern rhizospheres due to its superior growth-promoting, heavy-metal(loid) resistant, and antibiotic-tolerant characteristics. The strain that belongs to Cupriavidus sp. was determined by 16S rRNA sequencing and showed no morphological changes when grown with high concentrations of Sb (608.8 mg/L). The strain showed prominent indole acetic acid (IAA), phosphate-solubilizing abilities, and ACC deaminase activity under Sb stress. Moreover, IAA and soluble phosphate levels increased in the presence of 608.8 mg/L Sb. Inoculation of rape seedlings with Cupriavidus sp. S-8-2 enhanced several morphological and biochemical growth features compared to untreated seedlings grown under Sb stress. Inoculation of Cupriavidus sp. S-8-2 increased root weight by more than four-fold for fresh weight and over two-fold for dry weight, despite high environmental Sb. The strain also reduced Sb-mediated oxidative stress and malondialdehyde contents by reducing Sb absorption, thus alleviating Sb-induced toxicity. Environmental Scanning Electron Microscope (ESEM) imaging and dilution plating technique revealed Cupriavidus sp. S-8-2 is localized on the surface of roots. Identifying the Sb-resistant plant growth-promoting bacterium suggested its usefulness in the remediation of contaminated agricultural soil and for the promotion of crop growth. We highly recommend the strain for further implementation in field experiments.

The clinical development of antibody-drug conjugates for non-small cell lung cancer therapy.

Despite the emergence of molecular targeted therapy and immune checkpoint inhibitors as standard first-line treatments for non-small cell lung cancer (NSCLC), their efficacy in some patients is limited by intrinsic and acquired resistance. Antibody-drug conjugates (ADCs), a revolutionary class of antitumor drugs, have displayed promising clinical outcomes in cancer treatment. In 2022, trastuzumab deruxtecan (Enhertu) was approved for treating HER2-mutated NSCLC, thereby underscoring the clinical value of ADCs in NSCLC treatment strategies. An increasing number of ADCs, focusing on NSCLC, are undergoing clinical trials, potentially positioning them as future treatment options. In this review, we encapsulate recent advancements in the clinical research of novel ADCs for treating NSCLC. Subsequently, we discuss the mechanisms of action, clinical efficacy, and associated limitations of these ADCs.

Targeting Trop2 in solid tumors: a look into structures and novel epitopes.

Trophoblast cell surface antigen 2 (Trop2) exhibits limited expression in normal tissues but is over-expressed across various solid tumors. The effectiveness of anti-Trop2 antibody-drug conjugate (ADC) in managing breast cancer validates Trop2 as a promising therapeutic target for cancer treatment. However, excessive toxicity and a low response rate of ADCs pose ongoing challenges. Safer and more effective strategies should be developed for Trop2-positive cancers. The dynamic structural attributes and the oligomeric assembly of Trop2 present formidable obstacles to the progression of innovative targeted therapeutics. In this review, we summarize recent advancements in understanding Trop2's structure and provide an overview of the epitope characteristics of Trop2-targeted agents. Furthermore, we discuss the correlation between anti-Trop2 agents' epitopes and their respective functions, particularly emphasizing their efficacy and specificity in targeted therapies.

Current and future perspectives for Helicobacter pylori treatment and management: From antibiotics to probiotics.

Helicobacter pylori (H. pylori) is a Gram-negative anaerobic bacterium that colonizes the human stomach and is the leading cause of gastric diseases such as chronic gastritis and peptic ulcers, as well as the most definite and controllable risk factor for the development of gastric cancer. Currently, the regimen for H. pylori eradication has changed from triple to quadruple, the course of treatment has been extended, and the type and dose of antibiotics have been adjusted, with limited improvement in efficacy but gradually increasing side effects and repeated treatment failures in an increasing number of patients. In recent years, probiotics have become one of the most important tools for supporting intestinal health and immunity. Numerous in vitro studies, animal studies, and clinical observations have demonstrated that probiotics have the advantage of reducing side effects and increasing eradication rates in adjuvant anti-H. pylori therapy and are a valuable supplement to conventional therapy. However, many different types of probiotics are used as adjuncts against H. pylori, in various combinations, with different doses and timing, and the quality of clinical studies varies, making it difficult to standardize the results. In this paper, we focus on the risk, status, prevention, control, and treatment of H. pylori infection and review international consensus guidelines. We also summarize the available scientific evidence on using Limosilactobacillus reuteri (L. reuteri) as a critical probiotic for H. pylori treatment and discuss its clinical research and application from an evidence-based perspective.

Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer.

Trop2 is a transmembrane glycoprotein and calcium signal transducer with limited expression in normal human tissues. It is consistently overexpressed in a variety of malignant tumors and participates in several oncogenic signaling pathways that lead to tumor development, invasion, and metastasis. As a result, Trop2 has become an attractive therapeutic target in cancer treatment. The anti-Trop2 antibody-drug conjugate (Trodelvy™, sacituzumab govitecan) has been approved to treat metastatic triple-negative breast cancer. However, it is still unclear whether the success observed in Trop2-positive breast cancer could be replicated in other tumor types, owing to the differences in the expression levels and functions of Trop2 across cancer types. In this review, we summarize the recent progress on the structures and functions of Trop2 and highlight the potential diagnostic and therapeutic value of Trop2 beyond breast cancer. In addition, the promising novel Trop2-targeted agents in the clinic were discussed, which will likely alter the therapeutic landscape of Trop2-positive tumors in the future.

van der Waals integration of mixed-dimensional CeO2@Bi heterostructure for high-performance self-powered photodetector with fast response speed.

Heterostructures have been extensively investigated for optoelectronic devices owing to their fantastic physicochemical properties. Herein, a mixed-dimensional van der Waals heterostructure (vdWH) CeO2@Bi, 1D ceria (CeO2) loaded with 0D bismuth quantum dots (Bi QDs), is synthesized through a facile hydrothermal bottom-up method. It is found that the fabricated CeO2@Bi-based photoelectrochemical (PEC)-type photodetector (PD) shows self-powered photodetection capability with a fast photoresponse speed of 0.02 s. Besides, a photocurrent of 2.00 µA cm-2 and a photoresponsivity of 888.89 µA W-1 under 365 nm illumination are obtained. Furthermore, good long-term cycle stability is also observed after 1 month in a harsh environment, indicating the great potential for practical applications. These results are further supported by density functional theory (DFT) calculations. We believe that the presented work is expected to provide a new pathway for the future utilization of vdWHs for high-performance optoelectronics.

A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-CoV-2 virus and the Omicron variant BA.1 through a unique binding mode.

The major challenge to controlling the COVID pandemic is the rapid mutation rate of the SARS-CoV-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-CoV-2 variants. Here, we report a synthetic nanobody (named C5G2) obtained by phage display and subsequent antibody engineering. C5G2 has a single-digit nanomolar binding affinity to the RBD domain and inhibits its binding to ACE2 with an IC50 of 3.7 nM. Pseudovirus assays indicated that monovalent C5G2 could protect the cells from infection with SARS-CoV-2 wild-type virus and most of the viruses of concern, i.e., Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against Omicron BA.1 among all the variants, with an IC50 of 4.9 ng/mL. The cryo-EM structure of C5G2 in complex with the spike trimer showed that C5G2 binds to RBD mainly through its CDR3 at a conserved region that does not overlap with the ACE2 binding surface. Additionally, C5G2 binds simultaneously to the neighboring NTD domain of the spike trimer through the same CDR3 loop, which may further increase its potency against viral infection. Third, the steric hindrance caused by FR2 of C5G2 could inhibit the binding of ACE2 to RBD as well. Thus, this triple-function nanobody may serve as an effective drug for prophylaxis and therapy against Omicron as well as future variants.

Regulation of coordination and doping environment via target molecular transformation for boosting selective photocatalytic ability.

Here, a novel transformed CdO with low coordination and N doping environment was simply synthesized through the involvement of the target molecule tetracycline (TC). The results showed that the shedding of surface hydroxyl groups led to a low coordination environment, and N doping formed a new doping energy level, which increased the charge density and promoted the migration and separation of photo-generated carriers. Its photocatalytic performance was 4.32 times higher than that of hydroxy-rich CdO and the selectivity coefficient was 4.8. Combined with theoretical calculation and in situ Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) analysis, the significant improvement of selectivity was due to the interaction of the doped N atom with the methyl carbon in TC. This work provided a new idea for the simultaneous construction of low coordination environment and N-doped materials for efficient selective photocatalysis.

YTHDC1 is downregulated by the YY1/HDAC2 complex and controls the sensitivity of ccRCC to sunitinib by targeting the ANXA1-MAPK pathway.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) such as sunitinib are multitarget antiangiogenic agents in clear cell renal cell carcinoma (ccRCC). They are widely used in the treatment of advanced/metastatic renal cancer. However, resistance to TKIs is common in the clinic, particularly after long-term treatment. YTHDC1 is the main nuclear reader protein that binds with m6A to regulate the splicing, export and stability of mRNA. However, the specific role and corresponding mechanism of YTHDC1 in renal cancer cells are still unclear. METHODS: The Cancer Genome Atlas (TCGA) dataset was used to study the expression of YTHDC1 in ccRCC. Cell counting kit-8 (CCK-8), wound healing, Transwell and xenograft assays were applied to explore the biological function of YTHDC1 in ccRCC. Western blot, quantitative real time PCR (RT‒qPCR), RNA immunoprecipitation PCR (RIP-qPCR), methylated RIP-qPCR (MeRIP-qPCR) and RNA sequencing (RNA-seq) analyses were applied to study the YY1/HDAC2/YTHDC1/ANXA1 axis in renal cancer cells. The CCK-8 assay and xenograft assay were used to study the role of YTHDC1 in determining the sensitivity of ccRCC to sunitinib. RESULTS: Our results demonstrated that YTHDC1 is downregulated in ccRCC tissues compared with normal tissues. Low expression of YTHDC1 is associated with a poor prognosis in patients with ccRCC. Subsequently, we showed that YTHDC1 inhibits the progression of renal cancer cells via downregulation of the ANXA1/MAPK pathways. Moreover, we also showed that the YTHDC1/ANXA1 axis modulates the sensitivity of tyrosine kinase inhibitors. We then revealed that HDAC2 inhibitors resensitize ccRCC to tyrosine kinase inhibitors through the YY1/HDAC2 complex. We have identified a novel YY1/HDAC2/YTHDC1/ANXA1 axis modulating the progression and chemosensitivity of ccRCC. CONCLUSION: We identified a novel YY1/HDAC2/YTHDC1/ANXA1 axis modulating the progression and chemosensitivity of ccRCC.