Covalent Organic Framework-Structured Raman Probes for Ultrasensitive In Vivo Bioimaging.

Organic Raman probes, including polymers and small molecules, have attracted great attention in biomedical imaging owing to their excellent biocompatibility. However, the development of organic Raman probes is usually hindered by a mismatch between their absorption spectra and wavelength-fixed excitation, which makes it difficult to achieve resonance excitation necessary to obtain strong Raman signals. Herein, we introduce a covalent organic framework (COF) into the fine absorption spectrum regulation of organic Raman probes, resulting in their significant Raman signal enhancement. In representative examples, a polymer poly(diketopyrrolopyrrole-p-phenylenediamine) (DPP-PD) and a small molecule azobenzene are transformed into the corresponding COF-structured Raman probes. Their absorption peaks show an accurate match of less than 5 nm with the NIR excitation. As such, the COF-structured Raman probes acquire highly sensitive bioimaging capabilities compared to their precursors with negligible signals. By further mechanism studies, we discover that the crystallinity and size of COFs directly affect the π-conjugation degree of Raman probes, thus changing their bandgaps and absorption spectra. Our study offers a universal and flexible method for improving the signal performance of organic Raman probes without changing their structural units, making it more convenient to obtain the highly sensitive organic Raman probes for in vivo bioimaging.

Let-7b-5p promotes triptolide-induced growth-inhibiting effects in glioma by targeting IGF1R.

Glioma is one of the most common malignancies of the central nervous system. The therapeutic effect has not been satisfactory despite advances in comprehensive treatment techniques. Our previous studies have found that triptolide inhibits glioma proliferation through the ROS/JNK pathway, but in-depth mechanisms need to be explored. Recent studies have confirmed that miRNAs may function as tumor suppressor genes or oncogenes and be involved in cancer development and progression. In this study, we found that let-7b-5p expression levels closely correlated with WHO grades and overall survival in patients in tumor glioma-CGGA-mRNAseq-325, and the upregulation of let-7b-5p can inhibit the proliferation and induce apoptosis of glioma cells. Functionally, upregulation of let-7b-5p increased the inhibitory effect on cell viability and colony formation caused by triptolide and promoted the apoptosis rate of triptolide-treated U251 cells. Conversely, downregulation of let-7b-5p had the opposite effect, indicating that let-7b-5p is a tumor suppressor miRNA in glioma cells. Moreover, target prediction, luciferase reporter assays and functional experiments revealed that IGF1R was a direct target of let-7b-5p. In addition, upregulation of IGF1R reversed the triptolide-regulated inhibition of cell viability but promoted glioma cell apoptosis and activated the ROS/JNK signaling pathway induced by triptolide. The results obtained in vivo experiments substantiated those from the in vitro experiments. In summary, the current study provides evidence that triptolide inhibits the growth of glioma cells by regulating the let-7b-5p-IGF1R-ROS/JNK axis in vitro and in vivo. These findings may provide new ideas and potential targets for molecularly targeted therapies for comprehensive glioma treatment.

Hypoxia inducible factor-1α related mechanism and TCM intervention in process of early fracture healing.

As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients' physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine (TCM). In the early stage of fracture healing, the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α (HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms, in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.

KLF5­mediated expression of CARD11 promotes the progression of gastric cancer.

Caspase recruitment domain-containing protein 11 (CARD11) has been reported as functioning in multiple types of cancers. In the present study, the role and mechanism of CARD11 in gastric cancer was investigated. First, CARD11 expression in gastric cancer tissues and the association of CARD11 with overall survival were analyzed by the encyclopedia of RNA interactomes database. CARD11 expression in gastric cancer cells was detected by western blotting and reverse transcription-quantitative PCR analyses. After CARD11 silencing, cell proliferation was evaluated by Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine staining and flow cytometry analysis. Wound healing and Transwell assays were used to measure the capacities of cell migration and invasion. Additionally, the expression levels of epithelial-mesenchymal transition (EMT)-related proteins and mTOR-related proteins were detected by western blot analysis. HumanTFDB predicted the binding of the transcription factor Krüppel-like factor 5 (KLF5) to the CARD11 promoter, which was confirmed by dual luciferase reporter and chromatin immunoprecipitation assays. To explore the regulatory effects between KLF5 and CARD11, KLF5 was overexpressed to perform the rescue experiments in gastric cancer cells with CARD11 silencing. Results revealed that CARD11 was highly expressed in gastric cancer and was associated with poor prognosis. CARD11 interference inhibited the proliferation of gastric cancer cells and induced cell cycle arrest. Additionally, CARD11 silencing suppressed the migration, invasion and EMT of gastric cancer cells, accompanied by upregulated E-cadherin expression and downregulated N-cadherin and vimentin expression. Moreover, the transcription factor KLF5 positively regulated the transcription of CARD11 in gastric cancer. KLF5 overexpression reversed the effects of interference of CARD11 expression in gastric cancer cells to promote their proliferation, migration, invasion and EMT. KLF5 overexpression also led to a reduction in cell cycle arrest. Finally, interference of CARD11 expression suppressed the mTOR pathway, which was activated by KLF5. In conclusion, KLF5-mediated CARD11 promoted the proliferation, migration and invasion of gastric cancer cells.

Hybrid Model Teaching in the Postepidemic Period: From Nucleic Acid to Antigen for the Fluorescence Analysis of SARS-CoV-2.

Owing to the global spread of the coronavirus disease 2019 (COVID-19), education has shifted to distance online learning, whereas some face-to-face courses have been resumed with the improvement of the outbreak prevention and management situation, including a laboratory course for senior undergraduate students in chemical biology. Here, we present an innovative chemical biology experiment covering COVID-19 topics, which was created for third-year undergraduates. The basic principles of two nucleic-acid- and antigen-based diagnostic techniques for SARS-CoV-2 are demonstrated in detail. These experiments are designed to provide students with comprehensive knowledge of COVID-19 and related diagnoses in daily life. Crucially, the biosafety of this experimental manipulation was ensured by using artificial nucleic acids and recombinant protein. Furthermore, an interactive hybrid online-facing teaching model was designed to cover the key mechanism regarding PCR and serological tests of COVID-19. Finally, a satisfactory evaluation was obtained through a questionnaire, and simultaneously, reasonable improvements to the course design were suggested. The proposed curriculum provides all the necessary information for other instructors to create new courses supported by research.

Effective Potential and Superfluidity of Microwave-Shielded Polar Molecules.

We analytically show that the effective interaction potential between microwave-shielded polar molecules consists of an anisotropic van der Waals-like shielding core and a modified dipolar interaction. This effective potential is validated by comparing its scattering cross sections with those calculated using intermolecular potential involving all interaction channels. It is shown that a scattering resonance can be induced under microwave fields reachable in current experiments. With the effective potential, we further study the Bardeen-Cooper-Schrieffer pairing in the microwave-shielded NaK gas. We show that the superfluid critical temperature is drastically enhanced near the resonance. As the effective potential is suitable for exploring the many-body physics of molecular gases, our results pave the way for studies of the ultracold gases of microwave-shielded molecular gases.

Peptide functionalized actively targeted MoS2 nanospheres for fluorescence imaging-guided controllable pH-responsive drug delivery and collaborative chemo/photodynamic therapy.

The combination of imaging and different therapeutic strategies into one single nanoplatform often demonstrates improved efficacy over monotherapy in cancer treatments. Herein, a multifunctional nanoplatform (labelled as MPRD) based on molybdenum disulfide quantum dots (MoS2 QDs) is developed to achieve enhanced antitumor efficiency by integrating fluorescence imaging, tumor-targeting and synergistic chemo/photodynamic therapy (PDT) into one system. First, polyethylene glycol (PEG)ylated MoS2 QDs (MP) with desirable stability are synthesized via a hydrothermal process using MoS2 QDs and carboxyamino-terminated oligomeric PEG as raw materials. Then, MP were conjugated with arginine-glycine-aspartic acid (RGD) peptide via amidation to form a novel nanocarrier (MPR), which possesses strong blue fluorescence, good biocompatibility and ανß3 receptor-mediated targeting ability. More importantly, MPR generated reactive oxygen species under 808 nm laser activation to realize targeted antitumor PDT. Further doxorubicin (DOX) was loaded onto MPR, which endows MPRD with localized chemotherapy and pH-responsive drug release. The MPRD exhibits improved chemotherapy performance on HepG2 cells (overexpressing integrin ανß3) owing to enhanced cellular uptake mediated by ανß3 receptor and effective drug release triggered by intracellular pH. Notably, MPRD with efficient tumor targeting ability and high chemo/PDT efficacy under NIR laser irradiation is capable of inhibiting HepG2 tumor cell growth both in vitro and in vivo, which is significantly superior to each individual therapy. These findings demonstrate that MPRD holds great potential in effective cancer therapy.

Gut-on-a-chip for exploring the transport mechanism of Hg(II).

Animal models and static cultures of intestinal epithelial cells are commonly used platforms for exploring mercury ion (Hg(II)) transport. However, they cannot reliably simulate the human intestinal microenvironment and monitor cellular physiology in situ; thus, the mechanism of Hg(II) transport in the human intestine is still unclear. Here, a gut-on-a-chip integrated with transepithelial electrical resistance (TEER) sensors and electrochemical sensors is proposed for dynamically simulating the formation of the physical intestinal barrier and monitoring the transport and absorption of Hg(II) in situ. The cellular microenvironment was recreated by applying fluid shear stress (0.02 dyne/cm2) and cyclic mechanical strain (1%, 0.15 Hz). Hg(II) absorption and physical damage to cells were simultaneously monitored by electrochemical and TEER sensors when intestinal epithelial cells were exposed to different concentrations of Hg(II) mixed in culture medium. Hg(II) absorption increased by 23.59% when tensile strain increased from 1% to 5%, and the corresponding expression of Piezo1 and DMT1 on the cell surface was upregulated.

An evaluation of the effectiveness and safety of the Enhanced Recovery After Surgery (ERAS) program for patients undergoing colorectal surgery: a meta-analysis of randomized controlled trials.

Introduction: The Enhanced Recovery After Surgery (ERAS) protocol reduces surgery-related stress and hospital stays for complicated surgical patients. It speeds recovery, reduces readmissions, and lowers morbidity and mortality. However, the efficacy of ERAS in colorectal surgery is still debatable. Aim: To evaluate the effectiveness and safety of the ERAS program for patients undergoing colorectal surgery. Material and methods: PRISMA-compliant searches were performed on Medline, Embase, PubMed, the Web of Sciences, and the Cochrane Database up to March 2023. The included articles compared ERAS protocol results for colorectal surgery patients to those of conventional care. RevMan was used for the meta-analysis, and the Cochrane RoB Tool was used to assess the study quality. Results: The meta-analysis included 12 randomized controlled trials with a total of 1920 participants. There were 880 individuals in ERAS care and 1002 in conventional care. Weighted mean difference: -1.07 days, 95% confidence interval (CI): -1.53 to -0.60, p = 0.00001), overall length of stay: -4.12 days, 95% CI: -5.86 to -2.38, p = 0.00001), and post-operative hospital stay: -1.91 days, 95% CI: -4.73 to -0.91, p = 0.00001). Readmissions were higher in the ERAS group than in the normal care group (odds ratio (OR) = 1.20, 95% CI: 0.82 to 1.75, p = 0.35). Post-operative complications were lower in the ERAS care group (OR = 0.42; 95% CI: 0.27 to 0.65, p < 0.0001) and SSIs (OR = 0.75; 95% CI 0.52 to 1.08, p = 0.00001) than in the routine care group. Conclusions: Care provided in line with the ERAS protocol has been shown to be successful and beneficial for patients following colorectal surgery, because it minimizes post-operative problems and length of hospital stay, and improves outcomes.

Spatially Confined Fabrication of Polar Poly(Vinylidene Fluoride) Nanotubes.

Polar poly(vinylidene fluoride) (PVDF) nanotubes have attracted significant attention due to their excellent piezoelectric and ferroelectric properties, yet a tunable fabrication of homogeneous polar PVDF nanotubes remains a challenge. Here, a simple method is reported to fabricate polar PVDF nanotubes using anodize aluminum oxide (AAO) membranes as templates that are removed by etching in a potassium hydroxide (KOH) solution and then ageing at room temperature. PVDF nanotubes originally crystallized in the AAO membrane are pure α-crystals with very low crystallinity, yet after being released from the templates, the crystallinity of the nanotubes markedly increases with ageing at room temperature, leading to the formation of ß-PVDF crystals in a very short time, with the formation of γ crystals after longer ageing times. A large amount of γ crystals formed when the released PVDF nanotubes are heated to ≈130 °C. The formation of polar PVDF nanotubes released from the AAO templates treated with higher concentrations of alkaline solution results from the reaction of the surface of the PVDF nanotubes with the alkaline solution and structure reorganization under confined conditions. This large-scale preparation of ß- and γ-PVDF opens a new pathway to produce polar PVDF nanomaterials.

Engineering CRISPR/Cas13 System against RNA Viruses: From Diagnostics to Therapeutics.

Over the past decades, RNA viruses have been threatened people's health and led to global health emergencies. Significant progress has been made in diagnostic methods and antiviral therapeutics for combating RNA viruses. ELISA and RT-qPCR are reliable methods to detect RNA viruses, but they suffer from time-consuming procedures and limited sensitivities. Vaccines are effective to prevent virus infection and drugs are useful for antiviral treatment, while both need a relatively long research and development cycle. In recent years, CRISPR-based gene editing and modifying tools have been expanded rapidly. In particular, the CRISPR-Cas13 system stands out from the CRISPR-Cas family due to its accurate RNA-targeting ability, which makes it a promising tool for RNA virus diagnosis and therapy. Here, we review the current applications of the CRISPR-Cas13 system against RNA viruses, from diagnostics to therapeutics, and use some medically important RNA viruses such as SARS-CoV-2, dengue virus, and HIV-1 as examples to demonstrate the great potential of the CRISPR-Cas13 system.

Integrated Methylome and Transcriptome Analysis Provides Insights into the DNA Methylation Underlying the Mechanism of Cytoplasmic Male Sterility in Kenaf (Hibiscus cannabinus L.).

Cytoplasmic male sterility (CMS) is widely exploited in hybrid seed production. Kenaf is an important fiber crop with high heterosis. The molecular mechanism of kenaf CMS remains unclear, particularly in terms of DNA methylation. Here, using the anthers of a kenaf CMS line (P3A) and its maintainer line (P3B), comparative physiological, DNA methylation, and transcriptome analyses were performed. The results showed that P3A had considerably lower levels of IAA, ABA, photosynthetic products and ATP contents than P3B. DNA methylome analysis revealed 650 differentially methylated genes (DMGs) with 313 up- and 337 down methylated, and transcriptome analysis revealed 1788 differentially expressed genes (DEGs) with 558 up- and 1230 downregulated genes in P3A compared with P3B. Moreover, 45 genes were characterized as both DEGs and DMGs, including AUX,CYP, BGL3B, SUS6, AGL30 and MYB21. Many DEGs may be regulated by related DMGs based on methylome and transcriptome studies. These DEGs were involved in carbon metabolism, plant hormone signal transduction, the TCA cycle and the MAPK signaling pathway and were shown to be important for CMS in kenaf. These results provide new insights into the epigenetic mechanism of CMS in kenaf and other crops.

Fabrication of a Free-Standing MWCNT Electrode by Electric Field Force for an Ultra-Sensitive MicroRNA-21 Nano-Genosensor.

Abnormal expression of microRNA-21 (miR-21) is considered to be closely associated with the pathogenesis of colorectal cancer. However, great challenges do exist for the development of ultra-sensitive biosensors to detect the abnormal expression of miR-21 due to the low concentration in serum (fm level) at the early stage of colorectal cancer. Therefore, electric field force is used to rotate and rearrange random multi-walled carbon nanotubes (MWCNTs) at the microscale to improve the active sites of the electrode in this study. The free-standing MWCNTs are densely and high-orderly embedded into the bare electrode along the direction of the electric field. Compared to the bare electrode, the peak-current response of the free-standing MWCNT electrode improves by 150 times in cyclic voltammetric measurement. A nano-genosensor based on the free-standing MWCNT electrode is developed for measuring miR-21. The nano-genosensor for miR-21 shows an ultra-high sensitivity of 48.24 µA µm-1 , a wide linear range from 0.01 × 10-15 to 100 × 10-12 m, and a low detection limit of 1.2 × 10-18 m. The present nano-genosensor shows superior performance for miR-21 in human serum samples and demonstrates a potential application for the diagnosis of early stage colorectal cancer.

Recent advances of functional nucleic acid-based sensors for point-of-care detection of SARS-CoV-2.

This review focuses on critical scientific barriers that the field of point-of-care (POC) testing of SARS-CoV-2 is facing and possible solutions to overcome these barriers using functional nucleic acid (FNA)-based technology. Beyond the summary of recent advances in FNA-based sensors for COVID-19 diagnostics, our goal is to outline how FNA might serve to overcome the scientific barriers that currently available diagnostic approaches are suffering. The first introductory section on the operationalization of the COVID-19 pandemic in historical view and its clinical features contextualizes essential SARS-CoV-2-specific biomarkers. The second part highlights three major scientific barriers for POC COVID-19 diagnosis, that is, the lack of a general method for (1) designing receptors of SARS-CoV-2 variants; (2) improving sensitivity to overcome false negatives; and (3) signal readout in resource-limited settings. The subsequent part provides fundamental insights into FNA and technical tricks to successfully achieve effective COVID-19 diagnosis by using in vitro selection of FNA to overcome receptor design barriers, combining FNA with multiple DNA signal amplification strategies to improve sensitivity, and interfacing FNA with portable analyzers to overcome signal readout barriers. This review concludes with an overview of further opportunities and emerging applications for FNA-based sensors against COVID-19.

All-optical pulse switching with a periodically driven dissipative quantum system.

All-optical switching used to switch the input optical signals without any electro-optical conversion plays a vital role in the next generation of optical information processing devices. Even all-optical switchings (AOSs) with continuous input signals have been widely studied, all-optical pulse switchings (AOPSs) whose input signals are pulse sequences have rarely been investigated because of the time-dependent Hamiltonian, especially for dissipative quantum systems. In this paper, we propose an AOPS scheme, where a strong pulsed field is used to switch another pulsed input signal. With the help of Floquet-Lindblad theory, we identify the control field that can effectively turn on/off the input signal whose amplitude envelope is a square-wave (SW) pulse train in a three-level dissipative system. By comparing the properties of the AOPSs controlled by a continuous-wave (CW) field and an SW control field, we find that the SW field is more suitable to be a practical tool for controlling the input SW signal. It is interesting to impress that the switching efficacy is robust against pulse errors. The proposed protocol is readily implemented in atomic gases or superconducting circuits and corresponds to AOPSs or all-microwave pulse switchings.

A near-infrared triggered upconversion/MoS2 nanoplatform for tumour-targeted chemo-photodynamic combination therapy.

The combination of photodynamic therapy and chemotherapy has shown a great potential in cancer treatment. As a promising photosensitizer, MoS2 quantum dots (QDs) have limited application due to the low tissue penetration of its light absorbing wavelength in the ultraviolet and visible regions. For the purpose of utilizing MoS2QDs in higher NIR absorption region, herein, we constructed a core/shell nano-photosensitizer upconversion@MoS2 with doxorubicin loading. This nanoplatform can convert 980 nm NIR into visible light, activating MoS2QDs to produce reactive oxygen species through fluorescence resonance energy transfer. In addition, this nanoplatform presented good biocompatibility and tumor targeting after polyethylene glycol and folic acid modification. Interestingly, with pH-responsive drug release performance, this nanoplatform presented efficient chemotherapy effects. Thus, the tumour-targeted nanoplatform can achieve up-converted luminescence imaging guided chemo-photodynamic synergistic therapy effectively.

Functional nucleic acids as modular components against SARS-CoV-2: From diagnosis to therapeutics.

Coronavirus Disease 2019 (COVID-19), which poses an extremely serious global impact on human public healthcare, represents a high transmission and disease-causing viral infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is expanding at a rapid pace. Therefore, it is urgent for researchers to establish effective platforms for the assay and treatment of SARS-CoV-2. Functional nucleic acids (FNAs), comprising aptamers and nucleases, are of primary concern within the biological and medical communities owing of the distinctive properties of their target recognition and catalysis. This review will concentrate on the essential aspects of insights regarding FNAs and their technological expertise for the diagnostic and therapeutic utilization against COVID-19. We first offer a historical perspective of the COVID-19 pandemics, its clinical characteristics and potential biomarkers. Then, we briefly discuss the current diagnostic and therapeutic methodology towards COVID-19, highlighting the superiorities and existing shortcomings. After that, we introduce the key features of FNAs, and summarize recent progress of in vitro selection of FNAs for SARS-CoV-2 specific proteins and RNAs, followed by highlighting the general concept of translating FNAs into functional probes for diagnostic and therapeutic purposes. Then, we critically review the emerging FNAs-based diagnostic and therapeutic strategies that are fast, precise, efficient, and highly specific to fight COVID-19. Finally, we identify remaining challenges and offer future outlook of this emerging field.