Isolation and structure determination of a new bisabolane-type sesquiterpenoid with cytotoxicity from Penicillium oxalicum MZY-202312-521.

Endophytic fungi can produce attractive secondary metabolites with various biological activities that have contributed significantly to pharmacotherapy. In this study, three bisabolane-type sesquiterpenoids, including a new one, namely, inonotic acid C (1), together with previously reported compounds (S)-(+)-11-dehydrosydonic acid (2) and sydonic acid (3), were isolated from a marine algal-derived endophytic fungus Penicillium oxalicum MZY-202312-521. Their structures were determined by means of extensive spectroscopic analyses. The absolute configurations of inonotic acid C (1) were established by single-crystal X-ray diffraction method. In vitro cytotoxic experiments on human A549, MCF-7, HeLa, and HepG2 carcinoma cell lines were carried out. The new compound inonotic acid C (1) was found to possess strong inhibitory activity against the MCF-7 cell line, with an IC50 value of 7.7 µM.

Unveiling Collagen's Role in Breast Cancer: Insights into Expression Patterns, Functions and Clinical Implications.

Collagen, the predominant protein constituent of the mammalian extracellular matrix (ECM), comprises a diverse family of 28 members (I-XXVIII). Beyond its structural significance, collagen is implicated in various diseases or cancers, notably breast cancer, where it influences crucial cellular processes including proliferation, metastasis, apoptosis, and drug resistance, intricately shaping cancer progression and prognosis. In breast cancer, distinct collagens exhibit differential expression profiles, with some showing heightened or diminished levels in cancerous tissues or cells compared to normal counterparts, suggesting specific and pivotal biological functions. In this review, we meticulously analyze the expression of individual collagen members in breast cancer, utilizing Transcripts Per Million (TPM) data sourced from the GEPIA2 database. Through this analysis, we identify collagens that deviate from normal expression patterns in breast cancer, providing a comprehensive overview of their expression dynamics, functional roles, and underlying mechanisms. Our findings shed light on recent advancements in understanding the intricate interplay between these aberrantly expressed collagens and breast cancer. This exploration aims to offer valuable insights for the identification of potential biomarkers and therapeutic targets, thereby advancing the prospects of more effective interventions in breast cancer treatment.

Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice.

Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H1 receptor antagonist, but also acted as a selective antagonist of 5HTR2A. In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR2A/c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR2A. We conclude that spinal 5HTR2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR2A-specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR2A/c-FOS pathway. Our findings have supported that spinal 5HTR2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy.

Limitations and Innovative Application Methods of Surfactants for Solubilization of Poorly Water-Soluble Drugs.

Poor solubility of drugs leads to poor bioavailability and therapeutic efficiency. A large proportion of drugs that are not developed and marketed for use by patients are due to their extremely low solubility. Therefore, improving the solubility of poorly water-soluble drugs is one of the most important aspects of the field of drug research. With the continuous development of more and more formulation techniques and excipient applications, the solubility of poorly water-soluble drugs can be improved to a certain extent to obtain better pharmacokinetics and pharmacodynamics, including pH microenvironment regulation technology, inclusion complex, solid dispersion, nanotechnology, and application of surfactants. However, the most widely used among them is the application of surfactants. This technique can reduce the surface tension, improve wettability, and have a remarkable solubilizing ability after forming micelles. However, surfactants have also been found to possess certain limitations in solubilization. In this review, the factors affecting the solubilization of surfactants and limiting their application have been summarized from several aspects. These factors include drugs, additives, and media. Some ideas to solve these application limitations have also been put forward, which can lay a foundation for the wider application of surfactants in the future.

The effect of novel aromatic heterocycle substituted aminamidine derivatives on Necator americanus.

BACKGROUND: The efficacy of current drugs against hookworms at a single dose is highly variable across regions, age groups and infection intensity. Extensive and repeated use of these drugs also leads to potential drug resistance. Therefore, novel drugs are required for sustained disease control. OBJECTIVES: Novel aromatic heterocycle substituted aminamidine derivatives (AADs) were synthesized based on tribendimine (TBD), and their in vivo potency against Necator americanus was tested. METHODS: The efficacy of the AADs was tested in male hamsters. Oral and IV pharmacokinetic parameters were determined in male Sprague-Dawley rats. The proteomic profiles of N. americanus samples treated with AADs were compared using tandem mass tag-based quantitative proteomic analyses. RESULTS: Most AADs exhibited better anthelmintic activity than TBD at a single oral dose. Compound 3c exhibited improved solubility (>50×), and the curative dose was as low as 25 mg/kg. Similar to TBD, 3c was rapidly metabolized after oral administration and transformed into p-(1-dimethylamino ethylimino)aniline (dADT), an active metabolite against intestinal nematodes. dADT from 3c had better pharmacokinetic profiles than that from TBD and achieved an oral bioavailability of 99.5%. Compound 3c possessed rapid anthelmintic activity, clearing all worms within 24 h after an oral dose of 50 mg/kg. Quantitative proteomic analysis indicated that it might be related to ATP metabolism and cuticle protein synthesis. CONCLUSIONS: Compound 3c is a novel and promising compound against N. americanus in vivo.

Nonlinear optical diode effect in a magnetic Weyl semimetal.

Diode effects are of great interest for both fundamental physics and modern technologies. Electrical diode effects (nonreciprocal transport) have been observed in Weyl systems. Optical diode effects arising from the Weyl fermions have been theoretically considered but not probed experimentally. Here, we report the observation of a nonlinear optical diode effect (NODE) in the magnetic Weyl semimetal CeAlSi, where the magnetization introduces a pronounced directionality in the nonlinear optical second-harmonic generation (SHG). We demonstrate a six-fold change of the measured SHG intensity between opposite propagation directions over a bandwidth exceeding 250 meV. Supported by density-functional theory, we establish the linearly dispersive bands emerging from Weyl nodes as the origin of this broadband effect. We further demonstrate current-induced magnetization switching and thus electrical control of the NODE. Our results advance ongoing research to identify novel nonlinear optical/transport phenomena in magnetic topological materials and further opens new pathways for the unidirectional manipulation of light.

Clinical application of reserved gastric tube in neuroendoscopic endonasal surgery for pituitary tumor.

BACKGROUND: The neuroendoscopic approach has the advantages of a clear operative field, convenient tumor removal, and less damage, and is the development direction of modern neurosurgery. At present, transnasal surgery for sphenoidal pituitary tumor is widely used. But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts. AIM: To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors. METHODS: A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups, with 30 in each group. Experimental group: After anesthesia, a gastric tube was placed through the mouth under direct vision using a visual laryngoscope, and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection, during the operation, and when the patient recovered from anesthesia. Control group: Given the routine intraoperative care, no gastric tube was left. The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups; the scores of pharyngalgia after waking up, 6 h post-operation, and 24 h post-operation. The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared. The hospitalization days of the two groups were statistically compared. RESULTS: The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group, and the difference in the incidence of nausea was statistically significant (P < 0.05). After the patient woke up, the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group, and the difference was statistically significant (P < 0.05). The number of cases of postoperative cerebrospinal fluid leakage and intracranial infection was higher than that of the control group, but there was no statistically significant difference from the control group (P > 0.05). The hospitalization days of the experimental group was lower than that of the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Reserving a gastric tube in the endoscopic endonasal resection of pituitary tumors, combined with intraoperative and postoperative gastrointestinal decompression, can effectively reduce the incidence of nausea, reduce the number of vomiting and aspiration in patients, and reduce the complications of sore throat The incidence rate shortened the hospitalization days of the patients.

[Role of NLRP3 inflammasome in prevention and treatment of cognitive impairment-related diseases and traditional Chinese medicine intervention: a review].

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.

The coupling between healthspan and lifespan in Caenorhabditis depends on complex interactions between compound intervention and genetic background.

Aging is characterized by declining health that results in decreased cellular resilience and neuromuscular function. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of pharmacological anti-aging interventions. Here we assessed swimming performance as well as survival under thermal and oxidative stress across a nematode genetic diversity test panel to evaluate health effects for three compounds previously studied in the Caenorhabditis Intervention Testing Program and thought to promote longevity in different ways - NP1 (nitrophenyl piperazine-containing compound 1), propyl gallate, and resveratrol. Overall, we find the relationships among median lifespan, oxidative stress resistance, thermotolerance, and mobility vigor to be complex. We show that oxidative stress resistance and thermotolerance vary with compound intervention, genetic background, and age. The effects of tested compounds on swimming locomotion, in contrast, are largely species-specific. In this study, thermotolerance, but not oxidative stress or swimming ability, correlates with lifespan. Notably, some compounds exert strong impact on some health measures without an equally strong impact on lifespan. Our results demonstrate the importance of assessing health and lifespan across genetic backgrounds in the effort to identify reproducible anti-aging interventions, with data underscoring how personalized treatments might be required to optimize health benefits.

The effect of freeze-thaw action on the dynamic change of supra-permafrost water sources: A stable isotope perspective.

Due to the continuous degradation (gradual thawing) of permafrost, supra-permafrost water has become an important component of runoff that occurs in cold regions. However, current research has only focused on the amount of water provided by permafrost, and little has been reported regarding the source and formation mechanisms of supra-permafrost water. Due to the difficulty of observation and sampling in cold regions and insufficient data accumulation, model simulations face various difficulties in regard to solving problems related to hydrological processes. Considering the advantages of stable isotope tracer methods in hydrology, the source of supra-permafrost water in Qilian Mountain was analyzed based on 1,840 samples, and the source of supra-permafrost water was determined by end-member mixing analysis (EMMA). Negative line-conditioned excess (lc-excess), lower slope, and particularly the negative intercept of the evaporation line (EL) indicates strong evaporation effects on supra-permafrost water. Remarkably, the evolutionary process, influencing factors, and relationship with other water bodies all indicate that supra-permafrost water is replenished by precipitation, ground ice meltwater, and snow meltwater. The results indicated that from May to October, the contributions of precipitation to the supra-permafrost water were 79%, 83%, 90%, 84%, 87%, and 83%, respectively. Snow meltwater contributed 11%, 13%, 10%, 16%, 11%, and 9%, respectively. Permafrost degradation impacts the water cycle and can increase the minimum monthly runoff and increase groundwater storage. To mitigate the effects of this change, monitoring and early warning systems are essential for detecting signs of permafrost degradation in a timely manner so that appropriate measures can be taken. This may involve the use of remote-sensing technologies, sensor networks, and other methods for real-time monitoring. Establishing mechanisms for sharing information with the relevant departments is crucial. The research results provide scientific and technological support and aid in decision-making to mitigate the negative effects of continuous permafrost degradation in a changing environment.

Vegetation restoration strategies based on plant water use patterns.

The study on the water source of plants in alpine mountainous is of great significance to optimize the allocation and management of water resources, and can also provide important reference for ecological restoration and protection. However, the controls of water sources for different plants in alpine mountainous region remain poorly understood. Based on the advantages of stable isotope tracer and Bayesian (MixSIAR) model, the water source of plants in Qilian Mountains was quantitatively analyzed. The results showed that the water sources of plants in Qilian Mountain mainly included two parts: direct source and indirect source. The direct source is soil water, which provides most of the water that plants need. The highest contribution of soil water to shrubs was 80 %, followed by trees (73 %) and herbs (72 %). It is worth mentioning that trees mainly use deeper soil water (below 60 cm), shrubs mainly use surface and intermediate soil water (0-60 cm), and herbs mainly use surface soil water (0-40 cm). What is more noteworthy is that indirect sources, such as precipitation, glacier and snow meltwater, and groundwater, are also water sources that cannot be ignored for plant growth in study area. Shrubs and Herbs use more soil water in the range of 40-60 cm, which leads to the possibility of water competition between these two planting types. Therefore, attention should be paid to this phenomenon in the process of vegetation restoration and water resources management. Especially when planting or restoring artificial plants, it is necessary to consider the water use strategy of the two plants to avoid unnecessary water competition and water waste. This is of great significance for ecological stability and sustainable utilization of water resources in the study region.

Transversus Thoracic Muscle Plane Block For Postoperative Pain in Pediatric Cardiac Surgery: A Systematic Review And Meta-Analysis of Randomized And Observational Studies.

OBJECTIVES: Pediatric patients undergoing cardiac surgery usually experience significant surgical pain. Additionally, the effect of poor surgical analgesia creates a pain continuum that extends to the postoperative period. Transversus thoracic muscle plane block (TTMPB) is a novel plane block technique that can provide analgesia to the anterior chest wall. The analgesic role of TTMPB in pediatric cardiac surgery is still uncertain. A meta-analysis was conducted to determine the analgesic efficacy of this procedure. DESIGN AND SETTING: Systematic review and meta-analysis. PubMed, Embase, Web of Science, CENTRAL, WanFang Data, and the China National Knowledge Infrastructure were searched to November 2023, and the Grading of Recommendations Assessment, Development, and Evaluation approach was followed to evaluate the certainty of evidence. PARTICIPANTS: Eligible studies enrolled pediatric patients from 2 months to 12 years old scheduled to undergo cardiac surgery, and randomized them to receive a TTMPB or no block/sham block. MEASUREMENTS AND MAIN RESULTS: Six studies that enrolled 601 pediatric patients were included. Low-certainty evidence from randomized trials showed that, compared with no block or sham block, TTMPB in pediatric patients undergoing cardiac surgery may reduce postoperative modified objective pain score at 12 hours (weighted mean difference [WMD] -2.20, 95% CI -2.73 to -1.68) and 24 hours (WMD -1.76, 95% CI -2.09 to -1.42), intraoperative opioid consumption (WMD -3.83, 95% CI -5.90 to -1.76 µg/kg), postoperative opioid consumption (WMD -2.51, 95% CI -2.84 to -2.18 µg/kg), length of intensive care unit (ICU) stay (WMD -5.56, 95% CI -8.30 to -2.83 hours), and extubation time (WMD -2.13, 95% CI -4.21 to -0.05 hours). Retrospective studies provided very low certainty that the results were consistent with the randomized trials. CONCLUSION: Very low- to low-certainty evidence showed that TTMPB in pediatric patients undergoing cardiac surgery may reduce postoperative pain, opioid consumption, ICU length of stay, and extubation time.

Postbiotics in colorectal cancer: intervention mechanisms and perspectives.

Colorectal cancer (CRC) is a common malignancy affecting the gastrointestinal tract worldwide. The etiology and progression of CRC are related to factors such as environmental influences, dietary structure, and genetic susceptibility. Intestinal microbiota can influence the integrity of the intestinal mucosal barrier and modulate intestinal immunity by secreting various metabolites. Dysbiosis of the intestinal microbiota can affect the metabolites of the microbial, leading to the accumulation of toxic metabolites, which can trigger chronic inflammation or DNA damage and ultimately lead to cellular carcinogenesis and the development of CRC. Postbiotics are preparations of inanimate microorganisms or their components that are beneficial to the health of the host, with the main components including bacterial components (e.g., exopolysaccharides, teichoic acids, surface layer protein) and metabolites (e.g., short-chain fatty acids, tryptophan metabolite, bile acids, vitamins and enzymes). Compared with traditional probiotics, it has a more stable chemical structure and higher safety. In recent years, it has been demonstrated that postbiotics are involved in regulating intestinal microecology and improving the progression of CRC, which provides new ideas for the prevention and diagnosis of CRC. In this article, we review the changes in intestinal microbiota in different states of the gut and the mechanisms of anti-tumor activity of postbiotic-related components, and discuss the potential significance of postbiotics in the diagnosis and treatment of CRC. This reviews the changes and pathogenesis of intestinal microbiota in the development of CRC, and summarizes the relevant mechanisms of postbiotics in resisting the development of CRC in recent years, as well as the advantages and limitations of postbiotics in the treatment process of CRC.

Ginsenoside Rg1 relieves rat intervertebral disc degeneration and inhibits IL-1ß-induced nucleus pulposus cell apoptosis and inflammation via NF-κB signaling pathway.

The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1ß-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1). The pathological change was observed by HE and safranin O-fast green staining. The expression of IL-1ß, IL-6, TNF-α, MMP3, aggrecan, and collagen II was detected. The expression of NF-κB p65 in IVD tissues was detected. Rat NP cells were induced by IL-1ß to simulate IVDD environment and divided into the control group, IL-1ß group, and 20, 50, and 100 µmol/L Rg1 groups. The cell proliferation activity, the apoptosis, and the expression of IL-6, TNF-α, MMP3, aggrecan, collagen II, and NF-κB pathway-related protein were detected. In IVDD rats, ginsenoside Rg1 improved the pathology of IVD tissues; suppressed the expression of IL-1ß, IL-6, TNF-α, aggrecan, and collagen II; and inhibited the expression of p-p65/p65 and nuclear translocation of p65, to alleviate the IVDD progression. In the IL-1ß-induced NP cells, ginsenoside Rg1 also improved the cell proliferation and inhibited the apoptosis and the expression of IL-6, TNF-α, aggrecan, collagen II, p-p65/p65, and IκK in a dose-dependent manner. Ginsenoside Rg1 alleviated IVDD in rats and inhibited apoptosis, inflammatory response, and ECM degradation in IL-1ß-induced NP cells. And Rg1 may exert its effect via inhibiting the activation of NF-κB signaling pathway.

Postbiotics: emerging therapeutic approach in diabetic retinopathy.

Diabetic retinopathy (DR) is a prevalent microvascular complication in diabetic patients that poses a serious risk as it can cause substantial visual impairment and even vision loss. Due to the prolonged onset of DR, lengthy treatment duration, and limited therapeutic effectiveness, it is extremely important to find a new strategy for the treatment of DR. Postbiotic is an emerging dietary supplement which consists of the inactivate microbiota and its metabolites. Numerous animal experiments have demonstrated that intervention with postbiotics reduces hyperglycemia, attenuates retinal peripapillary and endothelial cell damage, improves retinal microcirculatory dysfunction, and consequently delays the progression of DR. More strikingly, unlike conventional probiotics and prebiotics, postbiotics with small molecules can directly colonize the intestinal epithelial cells, and exert heat-resistant, acid-resistant, and durable for storage. Despite few clinical significance, oral administration with postbiotics might become the effective management for the prevention and treatment of DR. In this review, we summarized the basic conception, classification, molecular mechanisms, and the advances in the therapeutic implications of postbiotics in the pathogenesis of DR. Postbiotics present great potential as a viable adjunctive therapy for DR.

Epigenetic marks or not? The discovery of novel DNA modifications in eukaryotes.

DNA modifications add another layer of complexity to the eukaryotic genome to regulate gene expression, playing critical roles as epigenetic marks. In eukaryotes, the study of DNA epigenetic modifications has been confined to 5mC and its derivatives for decades. However, rapid developing approaches have witnessed the expansion of DNA modification reservoirs during the past several years, including the identification of 6mA, 5gmC, 4mC, and 4acC in diverse organisms. However, whether these DNA modifications function as epigenetic marks requires careful consideration. In this review, we try to present a panorama of all the DNA epigenetic modifications in eukaryotes, emphasizing recent breakthroughs in the identification of novel DNA modifications. The characterization of their roles in transcriptional regulation as potential epigenetic marks is summarized. More importantly, the pathways for generating or eliminating these DNA modifications, as well as the proteins involved are comprehensively dissected. Furthermore, we briefly discuss the potential challenges and perspectives, which should be taken into account while investigating novel DNA modifications.

Effects of Germination on the Structure, Functional Properties, and In Vitro Digestibility of a Black Bean (Glycine max (L.) Merr.) Protein Isolate.

The utilization of black beans as a protein-rich ingredient presents remarkable prospects in the protein food industry. The objective of this study was to assess the impact of germination treatment on the physicochemical, structural, and functional characteristics of a black bean protein isolate. The findings indicate that germination resulted in an increase in both the total and soluble protein contents of black beans, while SDS-PAGE demonstrated an increase in the proportion of 11S and 7S globulin subunits. After germination, the particle size of the black bean protein isolate decreased in the solution, while the absolute value of the zeta potential increased. The above results show that the stability of the solution was improved. The contents of ß-sheet and ß-turn gradually decreased, while the content of α-helix increased, and the fluorescence spectrum of the black bean protein isolate showed a red shift phenomenon, indicating that the structure of the protein isolate and its polypeptide chain were prolonged, and the foaming property, emulsification property and in vitro digestibility were significantly improved after germination. Therefore, germination not only improves functional properties, but also nutritional content.

Magnetic Bimetallic Heterointerface Nanomissiles with Enhanced Microwave Absorption for Microwave Thermal/Dynamics Therapy of Breast Cancer.

Microwave thermotherapy (MWT) has shown great potential in cancer treatment due to its deep tissue penetration and minimally invasive nature. However, the poor microwave absorption (MA) properties of the microwave thermal sensitizer in the medical frequency band significantly limit the thermal effect of MWT and then weaken the therapeutic efficacy. In this paper, a Ni-based multilayer heterointerface nanomissile of MOFs-Ni-Ru@COFs (MNRC) with improved MA performance in the desired frequency band via introducing magnetic loss and dielectric loss is developed for MWT-based treatment. The loading of the Ni nanoparticle in MNRC mediates the magnetic loss, introducing the MA in the medical frequency band. The heterointerface formed in the MNRC by nanoengineering induces significant interfacial polarization, increasing the dielectric loss and then enhancing the generated MA performance. Moreover, MNRC with the strong MA performance in the desired frequency range not only enhances the MW thermal effect of MWT but also facilitates the electron and energy transfer, generating reactive oxygen species (ROS) at tumor sites to mediate microwave dynamic therapy (MDT). The strategy of strengthening the MA performance of the sensitizer in the medical frequency band to improve MWT-MDT provides a direction for expanding the clinical application of MWT in tumor treatment.

Visible-Light-Promoted α-C(sp3)-H Amination of Ethers with Azoles and Amides.

A visible-light-induced highly efficient C(sp3)-H amination of ethers with amides and azoles has been presented under mild conditions via a nitrogen- and carbon-centered radical coupling process. This protocol successfully utilizes 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and tert-butyl nitrite (TBN) as cocatalysts to deliver the aminated products of ethers under aerobic conditions. Notably, the developed reaction features the corresponding products in good yields (up to 93%) with a wide substrate scope. The mechanistic study indicates that C-N bond formation proceeds via a direct radical cross-coupling process. Preliminary biological activity analysis indicates that the resulting products have good and selective inhibitory activity on osteosarcoma (OS) cell lines and are promising for use as hits for drug discovery.

Spatiotemporal Mapping and Molecular Basis of Whole-brain Circuit Maturation.

Brain development is highly dynamic and asynchronous, marked by the sequential maturation of functional circuits across the brain. The timing and mechanisms driving circuit maturation remain elusive due to an inability to identify and map maturing neuronal populations. Here we create DevATLAS (Developmental Activation Timing-based Longitudinal Acquisition System) to overcome this obstacle. We develop whole-brain mapping methods to construct the first longitudinal, spatiotemporal map of circuit maturation in early postnatal mouse brains. Moreover, we uncover dramatic impairments within the deep cortical layers in a neurodevelopmental disorders (NDDs) model, demonstrating the utility of this resource to pinpoint when and where circuit maturation is disrupted. Using DevATLAS, we reveal that early experiences accelerate the development of hippocampus-dependent learning by increasing the synaptically mature granule cell population in the dentate gyrus. Finally, DevATLAS enables the discovery of molecular mechanisms driving activity-dependent circuit maturation.