Clinical significance of miR-9-5p in NSCLC and its relationship with smoking.

Purpose: Dysregulated expression of microRNA (miRNAs) in lung cancer has been wildly reported. The clinicopathologic significance of miR-9-5p in non-small-cell lung cancer (NSCLC) patients and its effect on NSCLC progression were explored in this study. Patients and methods: A total of 76 NSCLC patients were included. miR-9-5p expression was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Then, in vitro experiments including cell growth curve assays, colony formation assays, and transwell migration assays were performed. Further clinicopathological and prognostic values were explored using bioinformatics analysis of the TCGA database. Results: miR-9-5p expression was significantly increased in tumor tissues (both P < 0.0001). miR-9-5p expression was relatively higher in larger tumors (P = 0.0327) and in lung squamous carcinoma (LUSC) (P = 0. 0143). In addition, miR-9-5p was significantly upregulated in the normal lung tissues of cigarette smokers (P = 0.0099). In vitro, miR-9-5p was correlated with cell proliferation and migration. After that, bioinformatics analysis of the TCGA database indicated that miR-9-5p was correlated with tumor size (P = 0.0022), lymphatic metastasis (P = 0.0141), LUSC (P < 0.0001), and smoking history (P < 0.0001). Finally, a prognostic study indicated high miR-9-5p expression was correlated with poor prognosis in LUAD (P = 0.0121). Conclusion: Upregulation of miR-9-5p may have an oncogenic effect in NSCLC and may be related to smoking. The conclusion of this study may help find new prognostic and therapeutic targets for NSCLC and the exploration of the relationship between smoking and lung cancer.

Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients.

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

Effects of mindful breathing training combined with diary-based rehabilitation guidance in lung cancer patients undergoing surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Lung cancer surgery patients experience severe physical and mental symptoms, which seriously affect their quality of life and prognosis. Mindful breathing training is a promising strategy to improve their symptoms, but its effectiveness is affected by training compliance, and diary-based rehabilitation instruction has been shown to help improve training compliance. Therefore, the aim of this study was to evaluate the effects of mindful breathing training combined with diary-based rehabilitation guidance on improving perioperative outcomes in lung cancer surgery patients. MATERIALS AND METHODS: This single-center, assessor-blinded, prospective, three-arm randomized controlled trial was conducted from November 1, 2021 to November 1, 2022. Patients diagnosed with primary non-small cell lung cancer and scheduled for thoracoscopic surgery were randomly allocated to the combined intervention group, the mindful breathing group or the control group, with 34 patients in each group. The control group received routine care, while the mindful breathing group received mindful breathing training and routine care. The combined intervention group received both mindful breathing training and diary-based rehabilitation guidance, along with routine care. RESULTS: The per-protocol analysis revealed that patients in the mindful breathing group experienced statistically significant improvements in dyspnea, fatigue and anxiety. Patients in the combined intervention group had statistically significant improvements in dyspnea, fatigue, anxiety, depression, exercise self-efficacy and training compliance. CONCLUSION: This study provides evidence that mindful breathing training combined with diary-based rehabilitation guidance can be effective in improving perioperative outcomes in lung cancer patients. It can be applied in clinical practice in the future.

Bridging Atom Engineering for Low-Temperature Oxygen Activation in a Robust Metal-Organic Framework.

Achieving active site engineering at the atomic level poses a significant challenge in the design and optimization of catalysts for energy-efficient catalytic processes, especially for a reaction with two reactants competitively absorbed on catalytic active sites. Herein we show an example that tailoring the local environment of cobalt sites in a robust metal-organic framework through substituting the bridging atom from -Cl to -OH group leads to a highly active catalyst for oxygen activation in an oxidation reaction. Comprehensive characterizations reveal that this variation imparts drastic changes on the electronic structure of metal centers, the competitive reactant adsorption behavior, and the intermediate formation. As a result, exceptional low-temperature CO oxidation performance was achieved with T25(Temperature for 25% conversion) = 35°C and T100 (Temperature for 100% conversion) = 150°C, which stands out from existing MOF-based catalysts and even rivals many noble metal catalysts. This work provides a guidance for the rational design of catalysts for efficient oxygen activation for an oxidation reaction.

ZNF689 deficiency promotes intratumor heterogeneity and immunotherapy resistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive disease characterized by remarkable intratumor heterogeneity (ITH), which poses therapeutic challenges. However, the clinical relevance and key determinant of ITH in TNBC are poorly understood. Here, we comprehensively characterized ITH levels using multi-omics data across our center's cohort (n = 260), The Cancer Genome Atlas cohort (n = 134), and four immunotherapy-treated cohorts (n = 109). Our results revealed that high ITH was associated with poor patient survival and immunotherapy resistance. Importantly, we identified zinc finger protein 689 (ZNF689) deficiency as a crucial determinant of ITH formation. Mechanistically, the ZNF689-TRIM28 complex was found to directly bind to the promoter of long interspersed element-1 (LINE-1), inducing H3K9me3-mediated transcriptional silencing. ZNF689 deficiency reactivated LINE-1 retrotransposition to exacerbate genomic instability, which fostered ITH. Single-cell RNA sequencing, spatially resolved transcriptomics and flow cytometry analysis confirmed that ZNF689 deficiency-induced ITH inhibited antigen presentation and T-cell activation, conferring immunotherapy resistance. Pharmacological inhibition of LINE-1 significantly reduced ITH, enhanced antitumor immunity, and eventually sensitized ZNF689-deficient tumors to immunotherapy in vivo. Consistently, ZNF689 expression positively correlated with favorable prognosis and immunotherapy response in clinical samples. Altogether, our study uncovers a previously unrecognized mechanism underlying ZNF689 deficiency-induced ITH and suggests LINE-1 inhibition combined with immunotherapy as a novel treatment strategy for TNBC.

NAMPT regulates mitochondria function and lipid metabolism during porcine oocyte maturation.

Oocyte maturation defect can lead to maternal reproduction disorder. NAMPT is a rate-limiting enzyme in mammalian NAD+ biosynthesis pathway, which can regulate a variety of cellular metabolic processes including glucose metabolism and DNA damage repair. However, the function of NAMPT in porcine oocytes remains unknown. In this study, we showed that NAMPT involved into multiple cellular events during oocyte maturation. NAMPT expressed during all stages of porcine oocyte meiosis, and inhibition of NAMPT activity caused the cumulus expansion and polar body extrusion defects. Mitochondrial dysfunction was observed in NAMPT-deficient porcine oocytes, which showed decreased membrane potential, ATP and mitochondrial DNA content, increased oxidative stress level and apoptosis. We also found that NAMPT was essential for spindle organization and chromosome arrangement based on Ac-tubulin. Moreover, lack of NAMPT activity caused the increase of lipid droplet and affected the imbalance of lipogenesis and lipolysis. In conclusion, our study indicated that lack of NAMPT activity affected porcine oocyte maturation through its effects on mitochondria function, spindle assembly and lipid metabolism.

Drug-eluting beads versus conventional transarterial chemoembolization for the treatment of unresectable hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Transarterial chemoembolization (TACE) consists of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE). The benefits of the 2 treatments remain controversial. We conduct this meta-analysis to assess the efficacy and safety of the 2 methods for the patients with unresectable hepatocellular carcinoma. METHODS: In order to get a sound conclusion, we did thorough search all relevant studies with clear and stringent keyword criteria on the main databases. Objective tumor response rate, overall survival (OS) rate and adverse events were calculated and analyzed by RevMan 5.3 software. The random-effects or fixed-effects model was applied to pool the estimates according to Cochran Q test and I2 statistics. RESULTS: Twenty-four studies involving 2987 patients were eligible. DEB-TACE significantly improved objective tumor response rate (OR) (risk ratio [RR] = 1.27, 95% confidence interval [CI] [1.08, 1.48]; P = .003). While as for 1-year, 2-year, 3-year, 5-year OS rates, there were no evidences to indicate that DEB-TACE was significantly better than cTACE (RR = 1.05, 95% CI [0.99, 1.11]; P = .08), (RR = 1.02, 95% CI [0.93, 1.11]; P = .68), (RR = 0.92, 95% CI [0.77, 1.10]; P = .37), (RR = 0.92, 95% CI [0.47, 1.80]; P = .81), respectively. Adverse events rate (AE) was also similar in both groups (RR = 1.11, 95% CI [0.99,1.26]; P = .08). CONCLUSION: This meta-analysis demonstrates that DEB-TACE is not superior than cTACE regarding to OS and AE. However, DEB-TACE still be considered to provide a better objective tumor response rate for patients with unresectable hepatocellular carcinoma.

Curcumin derived from medicinal homologous foods: its main signals in immunoregulation of oxidative stress, inflammation, and apoptosis.

It has been for thousands of years in China known medicinal homologous foods that can be employed both as foods and medicines to benefit human and animal health. These edible herbal materials perform divert roles in the regulation of metabolic disorders, cancers, and immune-related diseases. Curcumin, the primary component derived from medicinal homologous foods like curcuma longa rhizome, is reported to play vital actions in organic activities, such as the numerous pharmacological functions including anti-oxidative stress, anti-inflammation and anti/pro-apoptosis in treating various diseases. However, the potential mechanisms of curcumin-derived modulation still need to be developed and attract more attention worldwide. Given that these signal pathways are enrolled in important bioactive reactions, we collected curcumin's last achievements predominantly on the immune-regulation signals with the underlying targetable strategies in the last 10 years. This mini-review will be helpful to accelerate curcumin and other extracts from medicinal homologous foods use in future human clinical applications.

[Critical Review on Environmental Occurrence and Photochemical Behavior of Substituted Polycyclic Aromatic Hydrocarbons].

Substituted polycyclic aromatic hydrocarbons (SPAHs) are a type of emerging pollutant that widely exist in the environment, which also exhibit carcinogenicity, mutagenicity, and teratogenicity. These pollutants belong to toxic pollutants because of their similar structures to polycyclic aromatic hydrocarbons (PAHs). Their environmental behavior and ecological risk have attracted increasing attention. Based on a literature review, we found a new breakthrough in the source, distribution, behavior, and risk of SPAHs with comparison to traditional pollutants PAHs. This paper reviewed the current research progress on the environmental occurrence and photochemical behavior of SPAHs. Their sources, formation mechanisms, and distribution characteristics in the multimedia environment were highlighted, and the photochemical transformation kinetics, pathways, and affecting factors of SPAHs in water, ice, and other media were discussed. Furthermore, the research prospects about the environmental behavior and risk of SPAHs were proposed.

[Effects of Straw Removal Measure on Soil Cd Bioavailability and Rice Cd Accumulation].

A field experiment was conducted in a lightly Cd-contaminated rice field in Ningxiang City, Hunan Province, to study the effects of straw removal measures on the soil Cd bioavailability and rice Cd accumulation. The results showed that:① two consecutive seasons of straw removal measures (T1-T4 treatments) effectively increased soil pH by 0.04-0.58 units, reduced soil organic matter by 0.68%-25.87%, and reduced the Cd content of rhizosphere soil by 3.76%-12.78%. ② The proportions of Cd in the acid-extractable fraction and oxidizable fraction decreased, and the proportion of Cd in the residual fraction increased. Furthermore, straw removal measures significantly reduced the bioavailability of Cd in rhizosphere soil, and the Cd contents in TCLP, DTPA, and CaCl2 extracts all significantly decreased compared with those in CK. ③ The straw removal measure could significantly reduce the content of DOC and Cd in soil pore water; and the contents of Cd in soil pore water decreased by 4.54%-40.00% and 2.75%-67.34% under the straw removal measure (T1-T4) for two consecutive seasons, respectively, indicating that DOC was one of the key factors affecting the content of Cd in soil pore water. ④ Two consecutive straw removal measures (T1-T4) reduced the accumulation of Cd in different rice tissues, among which, under the treatment of all straw and root removal (T4), the Cd contents of brown rice in late rice planting in 2020 and early rice planting in 2021 decreased by 18.52% and 39.69%, respectively. Therefore, full or partial removal of straw in Cd-contaminated rice fields is a powerful measure to reduce the risk of exceeding Cd levels in brown rice.

Inhibition of hippocampal cyclin-dependent kinase 5 activity ameliorates learning and memory dysfunction in a mouse model of bronchopulmonary dysplasia.

AIMS: Oxygen therapy plays a vital role in the development of bronchopulmonary dysplasia (BPD), which is the independent risk factor for neurodevelopment deficits in premature infants. However, the effect of hippocampal cyclin-dependent kinase 5 (CDK5) on BPD-associated neurodevelopment deficits is not fully understood. METHODS: Mice were placed in a hyperoxia chamber from postnatal Day 1 to Day 7. Hematoxylin and eosin staining was used to evaluate the lung histomorphological characteristics. Learning and memory functions of mice were detected by Morris water maze. TUNEL staining was applied to measure the number of apoptotic cells. The expression of CDK5, apoptosis-related protein, and neuroplasticity-related proteins were analyzed by Western blot. Golgi staining was used to assess the structure of dendritic spines. RESULTS: Hyperoxia-induced BPD mice showed a long-term learning and memory dysfunction, more severe neuronal apoptosis, and a decline of synaptic plasticity. Inhibition of CDK5 overactivation ameliorated cognitive deficits, neuronal apoptosis, and synaptic plasticity disorders in BPD mice. CONCLUSIONS: This study first found a vital role of CDK5 in BPD-associated neurodevelopmental disorders. Inhibition of CDK5 overexpression could effectively improve cognitive dysfunctions in BPD mice, which indicated that hippocampal CDK5 may be a new target for prevention and treatment in learning and memory dysfunction of BPD.

Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy.

Berberine (BBR), an isoquinoline alkaloid extracted from Coptidis Rhizoma, has a long history of treating dysentery in the clinic. Over the past two decades, the polytrophic, pharmacological, and biochemical properties of BBR have been intensively studied. The key functions of BBR, including anti-inflammation, antibacterial, antioxidant, anti-obesity, and even antitumor, have been discovered. However, the underlying mechanisms of BBR-mediated regulation still need to be explored. Given that BBR is also a natural nutrition supplement, the modulatory effects of BBR on nutritional immune responses have attracted more attention from investigators. In this mini-review, we summarized the latest achievements of BBR on inflammation, gut microbes, macrophage polarization, and immune responses associated with their possible tools in the pathogenesis and therapy of ulcerative colitis and cancer in recent 5 years. We also discuss the therapeutic efficacy and anti-inflammatory actions of BBR to benefit future clinical applications.

TSC/MTOR -associated Eosinophilic Renal Tumors Exhibit a Heterogeneous Clinicopathologic Spectrum : A Targeted Next-generation Sequencing and Gene Expression Profiling Study.

BACKGROUND: Several TSC1/2- or MTOR -mutated eosinophilic renal tumor subsets are emerging, including eosinophilic solid and cystic renal cell carcinoma (ESC RCC), eosinophilic vacuolated tumors (EVTs) and low-grade oncocytic tumors (LOTs). "Unclassified renal tumors with TSC/MTOR mutations" ( TSC -mt RCC-NOS) do not meet the criteria for other histomolecular subtypes. Whether these tumors represent a continuum of 1 TS C/ MTOR -mutation-associated disease is unknown. DESIGN: We evaluated the clinicopathologic and IHC profiles of 39 eosinophilic renal tumors with targeted DNA sequencing-confirmed TSC/MTOR mutations. Twenty-eight of these, plus 6 ChRCC, 5 RO, 5 ccRCC, 7 MiT RCC and 6 normal renal tissues, were profiled transcriptionally by RNA-seq. RESULTS: The 39 cases were reclassified based on morphological and IHC features as ESC RCC (12), EVT (9), LOT, (8) and TSC -mt RCC-NOS (10). The mutation profiles demonstrated consistency; ESC RCCs (12/12) had TSC mutations, and most LOTs (7/8) had MTOR mutations. Ten TSC -mt RCC-NOSs exhibited heterogeneous morphology, arising a differential diagnosis with other renal tumors, including MiT RCC, PRCC and epithelioid PEComa. RNA sequencing-based clustering segregated ESC RCC, EVT and LOT from each other and other renal tumors, indicating expression profile-level differences. Most TSC- mt RCC-NOSs (6/7) formed a mixed cluster with ESC RCC, indicating similar expression signatures; one TSC- mt RCC-NOS with unusual biphasic morphology clustered with EVT. CONCLUSIONS: We expanded the TSC/MTOR -associated eosinophilic renal tumor morphologic spectrum, identified gene mutation characteristics, and highlighted differential diagnosis challenges, especially with MiT RCC. ESC RCC, EVT, and LOT having distinct expression profiles. TSC -mt RCC-NOS may cluster with recognized TSC/MTOR -associated entities.

Multichannel Distribution and Transformation of Entangled Photons with Dielectric Metasurfaces.

Photonic quantum information processing relies on operating the quantum state of photons, which usually involves bulky optical components unfavorable for system miniaturization and integration. Here, we report on the transformation and distribution of polarization-entangled photon pairs with multichannel dielectric metasurfaces. The entangled photon pairs interact with metasurface building blocks, where the geometrical-scaling-induced phase gradients are imposed, and are transformed into two-photon entangled states with the desired polarization. Two metasurfaces, each simultaneously distributing polarization-entangled photons to spatially separated multiple channels M (N), may accomplish M×N channels of entanglement distribution and transformation. Experimentally we demonstrate 2×2 and 4×4 distributed entanglement states, including Bell states and superposition of Bell states, with high fidelity and strong polarization correlation. We expect this approach paves the way for future integration of quantum information networks.

Spin-Electric Coupling with Anisotropy-Induced Vanishment and Enhancement in Molecular Ferroelectrics.

Manipulating quantum properties by electric fields using spin-electric coupling (SEC) effects promises spatial addressability. While several studies about inorganic materials showing the SEC functionality have been reported, the vastly tunable crystal structures of molecular ferroelectrics provide a range of rationally designable materials yet to be exploited. In this work, Mn2+-doped molecular ferroelectrics are chosen to experimentally demonstrate the feasibility of achieving the quantum coherent SEC effect in molecular ferroelectrics for the first time. The electric field pulse applied between Hahn-echo pulses in electron paramagnetic resonance (EPR) experiments causes controllable phase shifts via manipulating of the zero-field splitting (ZFS) of the Mn(II) ions. Detailed investigations of the aMn crystal showed unexpected SEC vanishment and enhancement at different crystal orientations, which were elucidated by studying the spin Hamiltonian and magnetic anisotropy. With the enhanced SEC efficiency being achieved (0.68 Hz m/V), this work discovers an emerging material library of molecular ferroelectrics to implement coherent quantum control with selective and tunable SEC effects toward highly scalable quantum gates.

Meta-analysis of visual pretreatment for the prevention of emergence delirium in children undergoing ophthalmic surgery.

Objective: To evaluate the role of visual pretreatment in preventing emergence delirium in children receiving ophthalmic surgery. Methods: Four randomized controlled trials were identified in four databases, and a meta-analysis was conducted using RevMan 5.3. Results: The meta-analysis demonstrated a significantly lower incidence of postoperative emergence delirium (risk ratio: 0.39; 95% CI: 0.31-0.49) and propofol rescue (risk ratio: 0.29; 95% CI: 0.13-0.65) but comparable modified Yale Preoperative Anxiety Scale score (mean difference: -3.66; 95% CI: -9.96 to 2.65) and incidence of adverse events in the visual pretreatment group. Conclusion: Visual pretreatment is effective in preventing postoperative emergence delirium in children undergoing ophthalmic surgery without significant adverse effects and can also decrease the incidence of propofol rescue.

A Spinel Tin Ferrite with High Lattice-Oxygen Anchored on Graphene-like Porous Carbon Networks for Lithium-Ion Batteries with Super Cycle Stability and Ultra-fast Rate Performances.

A new type of nano-SnFe2O4 with stable lattice-oxygen and abundant surface defects anchored on ultra-thin graphene-like porous carbon networks (SFO@C) is prepared for the first time by an interesting freezing crystallization salt template method. The functional composite has excellent rate performance and long-term cycle stability for lithium-ion battery (LIB) anodes due to the stable structure, improved conductivity, and shortened migrating distance for lithium-ions, which are derived from the higher lattice-oxygen of SnFe2O4, abundant porous carbon networks and surface defects, and smaller nanoparticles. Under the ultra-high current density of 10, 15, and 20 A g-1 cycling for 1000 times, the SFO@C can provide high reversible capacities of 522.2, 362.5, and 361.1 mAh g-1, respectively. The lithium-ion storage mechanism of the composite was systematically studied for the first time by in situ X-ray diffraction (XRD), ex situ XRD and scanning electron microscopy (SEM), and density functional theory (DFT) calculations. The results indicate that the existence of Li2O and metallic Fe during the lithiation/delithiation process is a key reason for reducing the initial lithium-ion storage reversibility but increasing the rate performance and capacity stability in the subsequent cycles. DFT calculations show that lithium-ions are more easily adsorbed on the (111) crystal plane with a much lower adsorption energy of -7.61 eV than other planes, and the Fe element is the main acceptor of electrons. Moreover, the kinetics investigation indicates that the lithium-ion intercalation and deintercalation in SFO@C are mainly controlled by the pseudocapacitance behavior, which is favorable to enhancing the rate performance. The research provides a new strategy for designing LIB electrode materials with a stable structure and outstanding lithium-ion storage performance.

Genome-wide identification of Tomato Golden 2-Like transcription factors and abiotic stress related members screening.

BACKGROUND: Golden 2-Like (G2-like) transcription factors play an important role in plant development. However, the roles of these G2-like regulatory genes in response to abiotic stresses in tomato are not well understood. RESULTS: In this study, we identified 66 putative G2-like genes in tomato (Solanum lycopersicum) and classified them into 5 groups (I to V) according to gene structure, motif composition and phylogenetic analysis. The G2-like genes were unevenly distributed across all 12 chromosomes. There were nine pairs of duplicated gene segments and four tandem duplicated SlGlk genes. Analysis of the cis-regulatory elements (CREs) showed that the promoter regions of SlGlks contain many kinds of stress- and hormone-related CREs. Based on RNA-seq, SlGlks were expressed in response to three abiotic stresses. Thirty-six differentially expressed SlGlks were identified; these genes have multiple functions according to Gene Ontology (GO) analysis and are enriched mainly in the zeatin biosynthesis pathway. Further studies exhibited that silencing SlGlk16 in tomato would reduce drought stress tolerance by earlier wilted, lower superoxide dismutase (SOD), peroxidase (POD) activities, less Pro contents and more MDA contents. CONCLUSIONS: Overall, the results of this study provide comprehensive information on G2-like transcription factors and G2-like genes that may be expressed in response to abiotic stresses.