A New Solution to Intrusion Detection Systems Based on Improved Federated-Learning Chain

In the context of enterprise systems,intrusion detection(ID)emerges as a critical element driving the digital transformation of enterprises.With systems spanning various sectors of enterprises geographically dispersed,the necessity for seamless information exchange has surged significantly.The existing cross-domain solutions are challenged by such issues as insufficient security,high communication overhead,and a lack of effective update mechanisms,rendering them less feasible for prolonged application on resource-limited devices.This study proposes a new cross-domain collaboration scheme based on federated chains to streamline the server-side workload.Within this framework,individual nodes solely engage in training local data and subsequently amalgamate the final model employing a federated learning algorithm to uphold enterprise systems with efficiency and security.To curtail the resource utilization of blockchains and deter malicious nodes,a node administration module predicated on the workload paradigm is introduced,enabling the release of surplus resources in response to variations in a node’s contribution metric.Upon encountering an intrusion,the system triggers an alert and logs the characteristics of the breach,facilitating a comprehensive global update across all nodes for collective defense.Experimental results across multiple scenarios have verified the security and effectiveness of the proposed solution,with no loss of its recognition accuracy.

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

The Impact of Different Mining and Releasing Ratios on the Over-Support Pressure of Header Working Face

Through the theoretical analysis of overburden destabilization mechanism, FLAC 3D simplified plane numerical simulation method and field measurement method, we compared the relationship of overburden support pressure at 35 m of workface recovery, and the peak overburden support pressure decreased from 13.85 Mpa to 11.97 Mpa from 1:1 to 1:3. With the increase of mining ratio, the peak over-supporting pressure decreases: with the increase of top coal recovery thickness, the peak over-supporting pressure and the influence range will be further expanded, and the distance between the peak over-supporting pressure and the coal wall of the working face will be further increased and the high stress zone of the peak area will be expanded simultaneously.

Laws of strata energy release and corresponding safety warning system in metal mine

The strata deformation in mining area was monitored in Dabaoshan copper-iron mine,and an analytical method of strata energy release was put forward.On the basis of chaotic theory,by reconstructing the phase space for time series data of strata energy release,the saturated embedding dimension and the correlation dimension of the dynamic system were obtained to be 4 and 1.212 8,respectively,and the evolution laws of distances between phase points of strata energy release in the phase space were revealed.With grey theory,a prediction model of strata energy release was set up,the maximum error of which was less than 6.7%.The results show that there are chaotic characters in strata energy release during mining;after reconstructing phase space,the subtle changing characteristics of energy release can be magnified,and the internal rules can be fully demonstrated.According to the laws,a warning system for strata stability in mining area was established to provide a technical safeguard for safe mining.

Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

Unloading and successful treatment with bioresorbable stents during percutaneous coronary intervention:A case report

BACKGROUND With the development of percutaneous coronary intervention(PCI),the number of interventional procedures without implantation,such as bioresorbable stents(BRS)and drug-coated balloons,has increased annually.Metal drug-eluting stent unloading is one of the most common clinical complications.Comparatively,BRS detachment is more concealed and harmful,but has yet to be reported in clinical research.In this study,we report a case of BRS unloading and successful rescue.This is a case of a 59-year-old male with the following medical history:“Type 2 diabetes mellitus”for 2 years,maintained with metformin extended-release tablets,1 g PO BID;“hypertension”for 20 years,with long-term use of metoprolol sustained-release tablets,47.5 mg PO QD;“hyperlipidemia”for 20 years,without regular medication.He was admitted to the emergency department of our hospital due to intermittent chest pain lasting 18 hours,on February 20,2022 at 15:35.Electrocardiogram results showed sinus rhythm,ST-segment elevation in leads I and avL,and poor R-wave progression in leads V1–3.High-sensitivity troponin I level was 4.59 ng/mL,indicating an acute high lateral wall myocardial infarction.The patient’s family requested treatment with BRS,without implanta-tion.During PCI,the BRS became unloaded but was successfully rescued.The patient was followed up for 2 years;he had no episodes of angina pectoris and was in generally good condition.CONCLUSION We describe a case of a 59-year-old male experienced BRS unloading and successful rescue.By analyzing images,the causes of BRS unloading and the treatment plan are discussed to provide insights for BRS release operations.We discuss preventive measures for BRS unloading.

Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

RELEASE KINETICS OF MONOLITHIC MATRIX COATED WITH OUTER MEMBRANE SYSTEM

The reservoir-monolithic type of the controlled release systems is investigated currently,however,the existing kinetic model could not describe the release process well because the release kinetics is rather complicated.In this paper,a simplified release kinetic model for diffusion-controlled monolithic matrix coated with outer membrane systems is proposed and verified by the experimental data of mercaptopurinum release experiment.It shows that the model can well describe the release mechanism (the relative error is under 3%) when drug loading (C d) is above its solubility limit (C s).At the same time,the release characteristics of special cases (D mD f and D mD f) are discussed theoretically.When D mD f the release rate becomes constant,namely,zero order release,and the release rate is independent of the drug membrane.This result provides the theoretical basis for the system of zero order release as well as how to control the release rate and the amount of drug release.When D mD f,the release rate is dependent on the drug release coefficient in the monolithic matrix,solubility and drug loading but independent of the process in the outer membrane,and it is similar to monolithic matrix type.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Skeletal interoception in osteoarthritis

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the organism.Among its various forms,skeletal interoception specifically regulates the metabolic homeostasis of bones.Osteoarthritis(OA)is a complex joint disorder involving cartilage,subchondral bone,and synovium.The subchondral bone undergoes continuous remodeling to adapt to dynamic joint loads.Recent findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone,resulting in subchondral bone sclerosis in OA.The skeletal interoception is also a potential mechanism for chronic synovial inflammation in OA.In this review,we offer a general overview of interoception,specifically skeletal interoception,subchondral bone microenviroment and the aberrant subchondral remedeling.We also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA,as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

Use of an immunocapture device to detect cytokine release in discrete brain regions

Production of proinflammatory cytokines in the central nervous system is a key process in the neuroinflammatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling molecules play multiple roles in the immune response in the central nervous system including the orchestration of the sickness response to innate immune perturbations in the brain(Dantzer et al.,2008).

Biotin-modified Galactosylated Chitosan-gene Carrier in Hepatoma Cells Targeting Delivery

Our previous studies have successfully grafted biotin and galactose onto chitosan(CS)and synthesized biotin modified galactosylated chitosan(Bio-GC).The optimum N/P ratio of Bio-GC and plasmid DNA was 3:1.At this N/P ratio,the transfection efficiency in the hepatoma cells was the highest with a slow release effect.Bio-GC nanomaterials exhibit the protective effect of preventing the gene from nuclease degradation,and can target the transfection into hepatoma cells by combination with galactose and biotin receptors.The transfection rate was inhibited by the competition of galactose and biotin.Bio-GC nanomaterials were imported into cells’cytoplasm by their receptors,followed by the imported exogenous gene transfected into the cells.Bio-GC nanomaterials can also cause inhibitory activity in the hepatoma cells in the model of orthotopic liver transplantation in mice,by carrying the gene through the blood to the hepatoma tissue.Taken together,bio-GC nanomaterials act as gene vectors with the activity of protecting the gene from DNase degradation,improving the rate of transfection in hepatoma cells,and transporting the gene into the cytoplasm in vitro and in vivo.Therefore,they are efficient hepatoma-targeting gene carriers.

Emerging glacier forelands alter carbon dynamics on the Tibetan Plateau

The critical challenge of ongoing climate warming is resulting in glacier melting globally,a process accompanied by the formation of substantial glacier forelands.This phenomenon emerges as a pivotal area of study,especially in the Tibetan Plateau(TP),known as the Third Pole and the Asian Water Tower.In particular,the rapid retreat of temperate glaciers in the southeastern TP has led to the formation of expansive glacier forelands.These forelands are not merely evidence of climate shifts but are also key areas for transformative carbon dynamics.Moreover,the newly exposed land surface actively adjusts the balance of dissolved organic carbon,especially in meltwater,and influences the release of greenhouse gases from a range of sources including glacial lakes,subglacial sediments,and supraglacial/proglacial rivers.These processes play a crucial role in the dynamics of atmospheric carbon dioxide.Drawing from our intensive and detailed observations over several years,this perspective not only emphasizes the importance of the underexplored impact of glacier forelands on carbon cycles but also opens a window into understanding potential future trajectories in a warming world.

Peri-implant gas accumulation in response to magnesium-based musculoskeletal biomaterials:Reframing current evidence for preclinical research and clinical evaluation

Historically,the rapid degradation and massive gas release from magnesium(Mg)implants resulted in severe emphysema and mechanical failure.With the advent of new alloys and surface treatment methods,optimized Mg implants have re-entered clinics since last decade with reliable performance.However,the optimization aims at slowing down the degradation process,rather than exemption of the gas release.This study involved a systematic evaluation of current preclinical and clinical evidence,regarding the physical signs,symptoms,radiological features,pathological findings and complications potentially associated with peri±implant gas accumulation(PIGA)after musculoskeletal Mg implantation.The literature search identified 196 potentially relevant publications,and 51 papers were enrolled for further analysis,including 22 preclinical tests and 29 clinical studies published from 2005 to 2023.Various Mg-based materials have been evaluated in animal research,and the application of pure Mg and Mg alloys have been reported in clinical follow-ups involving multiple anatomical sites and musculoskeletal disorders.Soft tissue and intraosseous PIGA are common in both animal tests and clinical follow-ups,and potentially associated with certain adverse events.Radiological examinations especially micro-CT and clinical CT scans provide valuable information for quantitative and longitudinal analysis.While according to simulation tests involving Mg implantation and chemical processing,tissue fixation could lead to an increase in the volume of gas cavity,thus the results obtained from ex vivo imaging or histopathological evaluations should be interpreted with caution.There still lacks standardized procedures or consensus for both preclinical and clinical evaluation of PIGA.However,by providing focused insights into the topic,this evidence-based study will facilitate future animal tests and clinical evaluations,and support developing biocompatible Mg implants for the treatment of musculoskeletal disorders.

Fiber-optic drug delivery strategy for synergistic cancer photothermal-chemotherapy

Chemotherapy is one of the conventional treatments for cancer in clinical practice.However,poor delivery efficiency,systemic toxicity,and the lack of pharmacokinetic monitoring during treatment are the critical limitations of current chemotherapy.Herein,we reported a brand-new antitumor drug delivery strategy that harnesses an optical fiber endoscopically therapeutic probe.The fiber probe carries photosensitizers in the fiber core and antitumor agents on the fiber surface mediated by a temperature-responsive hydrogel film,giving rise to an activable photothermalchemotherapy that orchestrates the localized hyperthermia and thermal-stimuli drug release to the tumor lesion.Furthermore,the dynamical drug release and in-situ temperature can be real-time supervised through the built-in fiber sensors,including the reflective Mach–Zehnder interferometer and fiber Bragg grating,to visualize the therapy process and thus improve the safety of treatment.Compared with conventional methods,the fiber-optic drug delivery can adequately take advantage of the chemotherapeutics through collaboratively recruiting the photoheating-mediated enhanced permeability and the hydrogel particle-assisted high drug retention,shedding new light on a“central-toperipheral”drug pervasion and retention mechanism to destroy tumors completely.The fiber-optic chemotherapy strategy incorporates precise drug delivery,accurate controllability of drug release,high drug permeability and retention in tumor,low off-target rate,and real-time drug release and temperature feedback,performing a straightforward and precise photothermal-chemotherapy pathway.More than that,the proposed strategy holds tremendous promise to provide a revolutionized on-demand drug delivery platform for the highly efficient evaluation and screening of antitumor pharmaceuticals.

Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting

Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

Release characteristics and stabilization of heavy metals in antimony tailings in Yunnan Province,China

The pollution caused by the mining and smelting of heavy metals is becoming an increasingly severe environmental problem.In this study,the environmental risks of mine tailings were explored using typical antimony tailings(the depth of the sample taken from the ground to the deepest position of 120 cm)from the Zuoxiguo mine in Yunnan Province,Southwest China.The tailings were examined to explore the geological background,distribution characteristics,and release characteristics of heavy metals.Additionally,stabilizer treatments for heavy metals were investigated in consideration of waste treatment.The results showed that the contents of Sb and As(8.93×103 and 425 mg/kg,respectively)in the tailings were considerably higher than the local soil background values,suggesting that these metals pose a considerable threat to the surrounding environment.The geological background values of Cr,Cd,Pb,Cu,and Zn were relatively low.The results of static release showed that Sb,As,Cd,and Cr leached from the tailings more easily than Cu,Zn,and Pb under acidic conditions(pH=2.98).Geo-accumulation indices and potential ecological risk indices showed that Sb,As,Cd,and Pb were highly enriched in the tailings,whereas Cu,Cr,and Zn contents were relatively low.The single factor ecological risk index of the mining area showed that Sb and As are high ecological risk factors,whereas Cr,Cu,Zn,Cd,and Pb are not.The results of the orthogonal test results showed that by adding 15.0%(m/m)fly ash and 15.0%(m/m)zeolite powder to the quicklime and curing for 28 d,a significant stabilization effect was observed for Sb,As,and Pb.This study helps determine the priority control components for characteristic heavy metals in antimony tailings,and provides valuable insights regarding the formulation of appropriate mitigation strategies.

Microstructure Regulation and Combustion Performance Optimization of PVDF/Al Composite Powder by Non-covalent Functionalized Graphenes

Graphene prepared by non-covalent modification of sulfonated poly(ether-ether-ketone)(SPG)was combined with polyvinylidene fluoride(PVDF)/Al to improve the PVDF/Al thermal conductivity while reducing the effect of the thermal resistance at the graphene-polymer interface.The regulation rule of SPG with different contents on the energy release of fluorine-containing system was studied.When the content of SPG is 4%,the peak pressure and rise rate of SPG/PVDF/Al composite powder during ignition reach the maximum of 4845.28 kPa and 8683.58 kPa/s.When the content of SPG is 5%,the PVDF/Al composite powder is completely coated by SPG,and the calorific value of the material reachs the maximum of 29.094 kJ/g.Through the design and micro-control of the composite powder,the calorific value of the material can be effectively improved,but the improvement of the mass release rate still depends on the graphene content and surface modification state.

Research advances on encapsulation of probiotics with nanomaterials and their repair mechanisms on intestinal barriers

Probiotics participate in various physiological activities and contribute to body health.However,their viability and bioefficacy are adversely affected by gastrointestinal harsh conditions,such as gastric acid,bile salts and various enzymes.Fortunately,encapsulation based on various nanomaterials shows tremendous potential to protect probiotics.In this review,we introduced some novel encapsulation technologies involving nanomaterials in view of predesigned stability and viability,selective adhesion,smart release and colonization,and efficacy exertion of encapsulated probiotics.Furthermore,the interactions between encapsulated probiotics and the gastrointestinal tract were summarized and analyzed,with highlighting the regulatory mechanisms of encapsulated probiotics on intestinal mechanical barrier,chemical barrier,biological barrier and immune barrier.This review would benefit the food and pharmaceutical industries in preparation and utilization of multifunctional encapsulated probiotics.