Multi-center study of COVID-19 infection in elderly patients with lymphoma: on behalf of Jiangsu Cooperative Lymphoma Group (JCLG).

Elderly patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we retrospectively described the clinical features and outcomes of the first time infection of Omicron SARS-CoV-2 in 364 elderly patients with lymphoma enrolled in Jiangsu Cooperative Lymphoma Group (JCLG) between November 2022 and April 2023 in China. Median age was 69 years (range 60-92). 54.4% (198/364) of patients were confirmed as severe and critical COVID-19 infection. In univariable analysis, Age > 70 years (OR 1.88, p = 0.003), with multiple comorbidities (OR 1.41, p = 0.005), aggressive lymphoma (OR 2.33, p < 0.001), active disease (progressive or relapsed/refractory, OR 2.02, p < 0.001), and active anti-lymphoma therapy (OR 1.90, p < 0.001) were associated with severe COVID-19. Multiple (three or more) lines of previous anti-lymphoma therapy (OR 3.84, p = 0.021) remained an adverse factor for severe COVID-19 in multivariable analysis. Moreover, CD20 antibody (Rituximab or Obinutuzumab)-based treatments within the last 6 months was associated with severe COVID-19 in the entire cohort (OR 3.42, p < 0.001). Continuous BTK inhibitors might be protective effect on the outcome of COVID-19 infection (OR 0.44, p = 0.043) in the indolent lymphoma cohort. Overall, 7.7% (28/364) of the patients ceased, multiple lines of previous anti-lymphoma therapy (OR 3.46, p = 0.016) remained an adverse factor for mortality.

Proton Transfer Processes in 2-Butenenitrile Dimer Cation Studied by Mass-Selective Infrared Spectroscopy.

2-Butenenitrile (2-Bu) is a recently discovered crucial interstellar molecule. Herein, an abnormal NH band was observed in the infrared spectrum of the 2-Bu dimer cation, suggestive of a proton transfer reaction within the cluster. Through a comprehensive theoretical analysis of the IR spectrum of (2-Bu)2+, we discovered not only the formation of a new C-N bond through the attachment of one 2-Bu to another but also the occurrence of a proton transfer reaction in the cluster. This proton was identified as originating from the methyl group of the attaching 2-Bu in the cluster based on the analysis of IR spectra of (2-Bu)+ and [2-Bu-acrylonitrile (AN)]+. Furthermore, the detailed reaction process of this ion-molecule reaction is examined with theoretical calculation. This finding contributes significantly to our deeper understanding of ion-molecule reactions in the gas phase and the formation of nitrogen-containing prebiotic molecules in the interstellar medium.

Infrared Spectroscopy of Neutral and Cationic Benzonitrile-Methanol Binary Clusters in Supersonic Jets.

The formation of nitrogen-containing organic interstellar molecules is of great importance to reveal chemical processes and the origin of life on Earth. Benzonitrile (BN) is one of the simplest nitrogen-containing aromatic molecules in the interstellar medium (ISM) that has been detected in recent years. Methanol (CH3OH) exists widely in interstellar space with high reactivity. Herein, we measured the infrared (IR) spectra of neutral and cationic BN-CH3OH clusters by vacuum ultraviolet (VUV) photoionization combined with time-of-flight mass spectrometry. Combining IR spectra with the density functional theory calculations, we reveal that the BN-CH3OH intends to form a cyclic H-bonded structure in neutral clusters. However, after the ionization of BN-CH3OH clusters, proton-shared N···H···O and N···H···C structures are confirmed to form between BN and CH3OH, with the minor coexistence of H-bond and O-π structures. The formation of the proton-shared structure expands our knowledge of the evolution of the life-related nitrogen-containing molecules in the universe and provides a possible pathway to the further study of biorelevant aromatic organic macromolecules.

Effect of percutaneous vertebroplasty versus percutaneous kyphoplasty on post-operative wound pain in patients with osteoporotic vertebral compression fractures.

This research is intended to evaluate the efficacy of percutaneous vertebroplasty (PVP) versus percutaneous kyphoplasty (PKP) in osteoporotic vertebral compression fracture (OVCF), which is associated with post-operative pain. Eligible studies were screened by searching multiple databases and sources such as PubMed, Cochrane and EMBASE for search terms updated to October 2023, and relevant literature sources were searched. Randomized, controlled, prospective or retrospective, and cohort studies were eligible. For the analysis of the primary results, an analysis of the data was carried out, such as mean difference (MD) or odds ratio (OR), and 95% confidence interval (CI). In the present research, 1933 research was screened in 4 databases, and 30 articles were chosen to be examined under strict exclusion criteria. No statistical significance was found in the use of bone cement in the PVP group and PKP (MD, -0.60; 95% CI, -1.40, 0.21, p = 0.15); PKP was associated with a reduced risk of cement leak compared with PVP group (OR, 2.18; 95% CI, 1.38, 3.46, p = 0.0009); no statistical significance was found in the wound VAS score in PVP operation compared with that of PKP (MD, 0.16; 95% CI, -0.07, 0.40, p = 0.17); no statistical significance was found between the time of PVP operation and the time of PKP operation (MD, -2.65; 95% CI, -8.91, 3.60, p = 0.41). Compared with PVP technology, the PKP treatment of osteoporotic vertebral compression fractures reduces post-operative cement leakage, but there is no significant difference in the number of operative cement and wound VAS after operation. Nor did there appear to be a statistically significant difference in time between the two operations.

Ultrasensitive detection of thiram based on surface-enhanced Raman scattering via Au@Ag@Ag core/shell/shell bimetallic nanorods.

We developed a highly sensitive and stable SERS-active substrate of Au@Ag@Ag core/shell/shell nanorods, formed by encapsulating Au nanorods (Au NRs) into a bilayer silver shell with Raman reporter molecules (4-mercaptobenzoic acid (4-MBA) and thiram) in the shell-shell gap. The core/shell/shell nanostructures demonstrated a high SERS enhancement and easy assembly. The important role of the bilayer silver shell in boosting the SERS intensity and detection sensitivity was revealed by comparing the performances of the Au@Ag@4-MBA@Ag NRs, Au@Ag@4-MBA NRs, and Au@4-MBA NRs. The obtained Au@Ag@4-MBA@Ag NRs exhibited a significantly promoted SERS intensity, which could reach around 2.6 times and 240 times that of the Au@Ag@4-MBA NRs and Au@4-MBA NRs, where the enhancement factor was found to be strongly correlated with the shell thickness. The controllable plasma properties and SERS effect of the Au@Ag@4-MBA@Ag NRs could be optimized by adjusting the dose of silver nitrate. The SERS substrate comprising core/shell/shell nanorods was highly reproducible and stable (retaining 83% SERS intensity after one month). Moreover, the highly sensitive detection of the pesticide thiram with a detection limit as low as 1.74 × 10-9 M was achieved by taking advantage of the great SERS response of the core/shell/shell nanostructures, which was 1-2 orders of magnitude lower than for other SERS substrates. The developed SERS substrate could be readily extended to embed other target analytes into the core/shell/shell nanostructure for novel and sensitive detection. This study could enable fresh approaches toward next-generation ultrasensitive analyte detection.

Wild soybean salt tolerance metabolic model: Assessment of storage protein mobilization in cotyledons and C/N balance in the hypocotyl/root axis.

Salt stress has become one of the main factors limiting crop yield in recent years. The post-germinative growth is most sensitive to salt stress in soybean. In this study, cultivated and wild soybeans were used for an integrated metabonomics and transcriptomics analysis to determine whether wild soybean can resist salt stress by maintaining the mobilization of stored substances in cotyledons and the balance of carbon and nitrogen in the hypocotyl/root axis (HRA). Compared with wild soybean, the growth of cultivated soybean was significantly inhibited during the post-germinative growth period under salt stress. Integrating analysis found that the breakdown products of proteins, such as glutamate, glutamic acid, aspartic acid, and asparagine, increased significantly in wild soybean cotyledons. Asparagine synthase and fumarate hydratase genes and genes encoding HSP20 family proteins were specifically upregulated. In wild soybean HRA, levels of glutamic acid, aspartic acid, asparagine, citric acid, and succinic acid increased significantly, and the glutamate decarboxylase gene and the gene encoding carbonic anhydrase in nitrogen metabolism were significantly upregulated. The metabolic model indicated that wild soybean enhanced the decomposition of stored proteins and the transport of amino acids to the HRA in cotyledons and the GABA shunt to maintain carbon and nitrogen balance in the HRA to resist salt stress. This study provided a theoretical basis for cultivating salt-tolerant soybean varieties and opened opportunities for the development of sustainable agricultural practices.

Single-photon ionization induced C-C or C-N bond formation in pyrrole clusters.

The formation of photodimers of nitrogen heterocyclic compounds (NHCs) can partially explain the DNA damage due to radiation. Pyrrole and its derivatives, as major components of DNA, are used to understand the phenomena at the molecular level. With the aid of vacuum ultraviolet (VUV)-infrared (IR) spectroscopy and theoretical calculations, herein, we explore the possibility of the formation of a new C-C or C-N bond in pyrrole (py) clusters in a supersonic jet after single-photon ionization. Both neutral (py)2 and (py)3 clusters are stabilized by multiple interactions, such as N-H⋯π hydrogen bonds and π⋯π interactions. With 118 nm light ionization of the (py)2, we elucidate that the two py are more inclined to be stabilized by a newly formed C-C or C-N covalent bond, besides the π-stacked parallel structure of (py)2+. The (py)3+ with a C-C or C-N covalent bonded (py)2+ core mainly contributes to the IR spectrum of (py)3+. The present results are helpful to elucidate the mechanism of DNA damage at a molecular level.

Single-Photon Ionization Induced New Covalent Bond Formation in Acrylonitrile(AN)-Pyrrole(Py) Clusters.

The formation of nitrogen-containing organic compounds is crucial for understanding chemical evolution and the origin of life in the interstellar medium (ISM). In this study, we explore whether acrylonitrile (AN) and pyrrole (Py) can form new nitrogen-containing compounds after single-photon ionization in their gaseous clusters by vacuum ultraviolet (VUV)-infrared (IR) spectroscopy and theoretical calculations. The results show that a strong linear H-bond is formed in neutral AN-Py, while cyclic or bicyclic H-bonded networks are formed in the neutral AN-Py2 cluster. It is found that the structure containing a new C-C covalent bond between two moieties in (AN-Py)+ is formed besides the formation of H-bonded structures after AN-Py is ionized by VUV light. In (AN-Py2)+ cluster cations, new C-C or C-N covalent bonds tend to be formed between two Py, with (Py)2+ as the core in the cluster. The results reveal that new covalent bonds are more likely to be formed between two Py species when AN and Py are present in the cationic clusters. These results provide spectroscopic evidence of the formation of new nitrogen-containing organic compounds from AN and Py induced by VUV, which are helpful for our understanding of the formation of diverse prebiotic molecules in interstellar space.

An infrared spectroscopic study on gaseous molecular clusters: (Acrylonitrile-methanethiol)+ and (acrylonitrile-dimethyl sulfide).

The ion-molecule reaction is one of the most important pathways for the formation of new interstellar chemical species. Herein, infrared spectra of cationic binary clusters of acrylonitrile (AN) with methanethiol (CH3SH) and dimethyl sulfide (CH3SCH3) are measured and compared to those previous studies of AN and methanol (CH3OH) or dimethyl ether (CH3OCH3). The results suggest that the ion-molecular reactions of AN with CH3SH and CH3SCH3 only yield products with S…HN H-bonded or S∴N hemibond structures, rather than the cyclic products as observed in AN-CH3OH and AN-CH3OCH3 studied previously. The Michael addition-cyclization reaction between acrylonitrile and sulfur-containing molecules does not occur due to the weaker acidity of CH bonds in sulfur-containing molecules, which results from their weaker hyperconjugation effect compared to oxygen-containing molecules. The reduced propensity for the proton transfer from the CH bonds hinders the formation of the Michael addition-cyclization product that follows.

Development and validation of a risk prediction model for osteoporosis in elderly patients with type 2 diabetes mellitus: a retrospective and multicenter study.

BACKGROUND: This study aimed to construct a risk prediction model to estimate the odds of osteoporosis (OP) in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate its prediction efficiency. METHODS: This study included 21,070 elderly patients with T2DM who were hospitalized at six tertiary hospitals in Southwest China between 2012 and 2022. Univariate logistic regression analysis was used to screen for potential influencing factors of OP and least absolute shrinkage. Further, selection operator regression (LASSO) and multivariate logistic regression analyses were performed to select variables for developing a novel predictive model. The area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the performance and clinical utility of the model. RESULTS: The incidence of OP in elderly patients with T2DM was 7.01% (1,476/21,070). Age, sex, hypertension, coronary heart disease, cerebral infarction, hyperlipidemia, and surgical history were the influencing factors. The seven-variable model displayed an AUROC of 0.713 (95% confidence interval [CI]:0.697-0.730) in the training set, 0.716 (95% CI: 0.691-0.740) in the internal validation set, and 0.694 (95% CI: 0.653-0.735) in the external validation set. The optimal decision probability cut-off value was 0.075. The calibration curve (bootstrap = 1,000) showed good calibration. In addition, the DCA and CIC demonstrated good clinical practicality. An operating interface on a webpage ( https://juntaotan.shinyapps.io/osteoporosis/ ) was developed to provide convenient access for users. CONCLUSIONS: This study constructed a highly accurate model to predict OP in elderly patients with T2DM. This model incorporates demographic characteristics and clinical risk factors and may be easily used to facilitate individualized prediction.

Engineering highly efficient NIR-II FRET platform for Background-Free homogeneous detection of SARS-CoV-2 neutralizing antibodies in whole blood.

Förster or fluorescence resonance energy transfer (FRET) enables to probe biomolecular interactions, thus playing a vital role in bioassays. However, conventional FRET platforms suffer from limited sensitivity due to the low FRET efficiency and poor anti-interference of existing FRET pairs. Here we report a NIR-II (1000-1700 nm) FRET platform with extremely high FRET efficiency and exceptional anti-interference capability. This NIR-II FRET platform is established based on a pair of lanthanides downshifting nanoparticles (DSNPs) by employing Nd3+ doped DSNPs as an energy donor and Yb3+ doped DSNPs as an energy acceptor. The maximum FRET efficiency of this well-engineered NIR-II FRET platform reaches up to 92.2%, which is much higher than most commonly used ones. Owing to the all-NIR advantage (λex = 808 nm, λem = 1064 nm), this highly efficient NIR-II FRET platform exhibits extraordinary anti-interference in whole blood, and thus enabling background-free homogeneous detection of SARS-CoV-2 neutralizing antibodies in clinical whole blood sample with high sensitivity (limit of detection = 0.5 µg/mL) and specificity. This work opens up new opportunities for realizing highly sensitive detection of various biomarkers in biological samples with severe background interference.

3D matrix promotes cell dedifferentiation into colorectal cancer stem cells via integrin/cytoskeleton/glycolysis signaling.

The potential for tumor occurrence triggered by cancer stem cells (CSCs) has emerged as a significant challenge for human colorectal cancer therapy. However, the underlying mechanism of CSC development remains controversial. Our study provided evidence that the bulk of tumor cells could dedifferentiate to CSCs and reacquire CSC-like phenotypes if cultured in the presence of extracellular matrix reagents, such as Matrigel and fibrin gels. In these 3D gels, CD133- colorectal cancer cells can regain tumorigenic potential and stem-like phenotypes. Mechanistically, the 3D extracellular matrix could mediate cytoskeletal F-actin bundling through biomechanical force associated receptors integrin ß1 (ITGB1), contributing to the release of E3 ligase tripartite motif protein 11 (TRIM11) from cytoskeleton and degradation of the glycolytic rate-limiting enzyme phosphofructokinase (PFK). Consequently, PFK inhibition resulted in enhanced glycolysis and upregulation of hypoxia-inducible factor 1 (HIF1α), thereby promoting the reprogramming of stem cell transcription factors and facilitating tumor progression in patients. This study provided novel insights into the role of the extracellular matrix in the regulation of CSC dedifferentiation in a cytoskeleton/glycolysis-dependent manner.

NORAD-sponged miR-378c alleviates malignant behaviors of stomach adenocarcinoma via targeting NRP1.

BACKGROUND: Stomach adenocarcinoma (STAD) is the most common type of gastric cancer (GC), with a high recurrence rate and poor prognosis, but the potential indicators for STAD are insufficient. METHODS: Herein, we found that MicroRNA-378c (miR-378c) was lowly expressed in STAD, and the low expression of miR-378c was highly correlated with poor overall survival (OS), T stage, Reflux history, DSS events and PFI events of STAD patients. RESULTS: In addition, univariate analysis displayed that miR-378c was significantly associated with OS (Hazard ratio 0.735; 95% CI, 0.542-0.995; P = 0.046). Furthermore, it was validated that miR-378c inhibition accelerated STAD cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), while they were suppressed by miR-378c overexpression. Mechanistically, Neuropilin 1 (NRP1) was confirmed as the target of miR-378c, and Lnc-NORAD was identified as its sponger. More importantly, NORAD-mediated miR-378c inhibited malignant behaviors of STAD both in vitro and in vivo. CONCLUSIONS: Collectively, these results suggest miR-378c as a promising indicator for the treatment of STAD.

Visualizing the distribution of curcumin in the root of Curcuma longa via VUV-postionization mass spectrometric imaging.

Curcumin is a dietary spice and coloring agent widely used in food and herbal medicine. Herein, we visualized the distribution of curcumin in fresh Curcuma longa (turmeric) root sections using the state-of-the-art vacuum-ultraviolet (VUV, 118 nm) single photon-postionization mass spectrometric imaging method. Compared with other mass spectrometric imaging methods, the proposed method does not require any sample pre-treatment. The proposed approach could be more conducive to in situ detection of small molecules. The mass spectroscopic imaging (MSI) images of curcumin sections with a lateral resolution of 100 µm indicated that the concentrations of curcumin decreased from the phloem to the xylem of the root. We also show MS imaging of curcumin in the turmeric root at different maturity periods, revealing the transformation of this endogenous species. The result of quantitative analysis indicates that the total curcumin content of the mature turmeric root is estimated to be 3.43%, which is consistent with the previous report that the content of curcumin in the turmeric root is estimated between 3% and 5%. The report indicated that the proposed method of VUV single photon postionization MSI can be used to explore the metabolic process of plants, which is critical for herbal farming, harvest, and its ingredient extraction.

Ultrasound-targeted microbubble destruction (UTMD)-mediated miR-150-5p attenuates oxygen and glucose deprivation-induced cardiomyocyte injury by inhibiting TTC5 expression.

BACKGROUND: Cardiomyocyte injury is a typical feature in cardiovascular diseases. Changes in cardiomyocytes strongly affect the progression of cardiovascular diseases. This work aimed to investigate the biological function and potential mechanism of action of miR-150-5p in cardiomyocytes. METHODS AND RESULTS: A myocardial ischemia (MI) injury rat model was constructed to detect miR-150-5p and tetratricopeptide repeat domain 5 (TTC5) expression during heart ischemia injury. Primary cardiomyocytes were isolated for in vitro study. CCK-8 assays were used to detect cardiomyocyte viability. Western blots were used to detect TTC5 and P53 expression. qPCR was utilized to measure RNA expression of miR-150-5p and TTC5. The TUNEL assay was used to determine cell apoptosis. ELISA was used to determine cytokine (TNF-α, IL-1ß, IL-6, and IL-8) levels in heart tissues and cell culture supernatants. A dual-luciferase reporter assay was carried out to verify the binding ability between miR-150-5p and TTC5. Oxygen-glucose deprivation (OGD) treatment significantly inhibited cell viability. Ultrasound-targeted microbubble destruction (UTMD)-mediated uptake of miR-150-5p inverted these results. Additionally, UTMD-mediated uptake of miR-150-5p retarded the effects of OGD treatment on cell apoptosis. Besides, UTMD-mediated uptake of miR-150-5p counteracted the effects of OGD treatment on the inflammatory response by regulating cytokine (TNF-α, IL-1ß, IL-6, and IL-8) levels. For the mechanism of the protective effect on the heart, we predicted and confirmed that miR-150-5p bound to TTC5 and inhibited TTC5 expression. CONCLUSIONS: UTMD-mediated uptake of miR-150-5p attenuated OGD-induced primary cardiomyocyte injury by inhibiting TTC5 expression. This discovery contributes toward further understanding the progression of primary cardiomyocyte injury.

Spectroscopic evidence of S∴N and S∴O hemibonds in heterodimer cations.

Computational and condensed phase experimental evidence for the existence of S∴N and S∴O hemibonded structures has been reported previously, but no gas phase experimental evidence has been reported. To experimentally explore the existence of the S∴N and S∴O hemibonds in the gas phase, we recorded the infrared photodissociation action spectra of four cationic clusters: [CH3SH-NH3]+, [CH3SCH3-NH3]+, [CH3SCH3-H2O]+, and [CH3OCH3-H2O]+. Combined with the calculation results, it is found that the S∴N hemibonded structure is competitive with the S⋯HN H-bonded structure, though only the latter structure is actually observed in [CH3SH-NH3]+. The spectral and theoretical results show that hemibonds can form between the second- (oxygen or nitrogen) and the third-period elements (sulfur) in the heterodimer clusters of [CH3SCH3-NH3]+ and [CH3SCH3-H2O]+. However, the S∴N and S∴O hemibonded structures are found competitive with the C⋯HN and CH⋯O H-bonded structures, respectively, and both the structures coexist. On the other hand, the O∴O hemibonded structure is much less stable than other hydrogen bonded (H-bonded) structures in [CH3OCH3-H2O]+, and it shows no clear contribution to the observed spectrum. This study provides direct spectroscopic evidence for the existence of S∴N and S∴O hemibonds in the gas phase and their competition with the H-bonds, which may be also fundamentally important in biological processes.

Spectroscopic evidence of the C-N covalent bond formed between two interstellar molecules (ISM): acrylonitrile and ammonia.

Acrylonitrile (AN) and ammonia (NH3) are two important nitrogen-containing interstellar molecules in outer space, especially on Titan. Herein, we measured infrared (IR) spectra of neutral and cationic AN-NH3 complexes by VUV single-photon ionization combined with time-of-flight mass spectrometry. On combining IR spectra with the theoretical calculations, we found that the molecules prefer to form a single-ring cyclic H-bonded structure in the neutral AN-NH3 and (AN)2-NH3 clusters. However, after ionization of AN-NH3 and (AN)2-NH3 clusters, a new C-N-covalent bond is confirmed to form directly between AN and NH3, without any energy barrier in the cationic complexes. Moreover, in the ionized (AN)2-NH3 cluster, the covalent C-N bond prefers to form between AN and NH3 rather than the two AN groups. These results provide spectroscopic evidence of AN forming a new molecule with NH3, induced by VUV radiation. The formation of the new C-N bond broadens our knowledge on the evolution of the prebiotic nitrogen-containing molecules in space.

Proton Transfer in Nitromethane-Ammonia Clusters under VUV Single-Photon Ionization Explored by Infrared Spectroscopy and Theoretical Calculations.

It is known that the acidity and reactivity of the CH bond can be enhanced after ionization. Also, this property plays a pivotal role in proton transfer reaction and in the formation of new molecules. Herein, infrared spectroscopy and high-precision quantum chemical calculations are used to study the neutral and cationic clusters of nitromethane-ammonia (CH3NO2-NH3). It is found that in the neutral cluster, CH3NO2 and NH3 are mainly bonded by three intermolecular hydrogen bonds, in which electrostatic contribution plays a major role. After vacuum ultraviolet (VUV) single-photon ionization of CH3NO2-NH3, the positive charge redistributes from the ionized nitrogen atom of NH3 to the CH3NO2 molecule immediately. Then, the proton of CH3NO2 transfers to NH3 to form a proton-transferred type structure CH2NO2-NH4+, without any effective energy barrier, due to the positive hyperconjugation of cationic nitromethane. A closed loop of positive charge transfer takes place in the CH3NO2-NH3 cluster after VUV ionization. The present work demonstrates that both the proton transfer reaction and charge transfer process have occurred in the ionized CH3NO2-NH3 cluster. Moreover, it is found that the proton transfer reaction is a result of the highly acidic CH bond caused by hyperconjugation between the σ (CH) bond and π orbital.

Resveratrol inhibits necroptosis by mediating the TNF-α/RIP1/RIP3/MLKL pathway in myocardial hypoxia/reoxygenation injury.

Resveratrol (RES) protects myocardial cells from hypoxia/reoxygenation (H/R)-caused injury. However, the mechanism of this effect has not been clarified. Thus, in this study, we aimed to determine whether RES attenuates H/R-induced cell necroptosis by inhibiting the tumor necrosis factor-alpha (TNF-α)/receptor-interacting protein kinase 1 (RIP1)/RIP3/mixed-lineage kinase domain-like (MLKL) signaling pathway. Rat myocardial ischemia/reperfusion (I/R) models and H/R-injured cell models were constructed. Our study showed that myocardial H/R injury significantly increased the levels of TNF-α, RIP1, RIP3, and p-MLKL/MLKL by western blot analysis. Cell viability assay and 4,6-dianmidino-2-phenylindole (DAPI)-propidium iodide staining showed that the cell viability was decreased, and necroptosis was increased after myocardial H/R injury. The expressions of TNF-α, RIP1, RIP3, and p-MLKL/MLKL in H/R myocardial cells treated with different concentrations of RES were significantly downregulated. In addition, we also found that the cell viability was increased and necroptosis was decreased in dose-dependent manners when H/R-injured cells were treated with RES. In addition, the enhanced effect of TNF-α on necroptosis in myocardial H/R-injured cells was improved by RES, and the effect of RES was confirmed in vivo in I/R rats. This study also showed that RES suppresses necroptosis in H9c2 cells, which may occur through the inhibition of the TNF-α/RIP1/RIP3/MLKL signaling pathway. Our data suggest that necroptosis is a promising therapeutic target and may be a promising therapeutic target for the treatment of myocardial I/R injury.

Preparation of Aptamer Responsive DNA Functionalized Hydrogels for the Sensitive Detection of α-Fetoprotein Using SERS Method.

Hepatocellular carcinoma (HCC), which is one of the three major cancers, has attracted growing attention due to its high mortality, health care cost, and circumscribed therapeutic methods. Hence, the development of a fast, accurate, and flexible method to detect α-fetoprotein (AFP), the specific marker of HCC, is significant for diagnosis and treatment of cancer. Here, we constructed a novel SERS biosensing platform combining the target-responsive DNA hydrogel for the sensitive detection of AFP. The linker strand in DNA hydrogel is an aptamer that can specifically recognize AFP and accurately control the release of immunoglobulin G (IgG) encapsulated in hydrogel. In the presence of AFP, the hydrogels were disentangled and the IgG was released. Thereafter, the released IgG was captured by SERS probes and biofunctional magnetic beads through formation of sandwich-like structures, resulting in the signal of Raman tags decreasing in the supernatant after magnetic separation. Due to the ultrahigh sensitivity of the SERS biosensor, the proposed method has a wide detection linear range (50 pg/mL to 0.5 µg/mL) and a detection limit down to 50 pg/mL. Moreover, the sequence of the linker strand in the DNA hydrogel can be specifically encoded into a new aptamer that responds to other cancer markers. This convenient and inexpensive detection method provides a new strategy for the detection of tumor markers.