Effectiveness of the six-step approach guided online training program to improve knowledge of Mycoplasma pneumoniae pneumonia among pediatricians: a pretest-posttest study.

Background: In 2023, China witnessed an earlier and more widespread outbreak of Mycoplasma pneumoniae pneumonia (MPP). To address this situation, an online training program was designed to enhance the knowledge of MPP among pediatricians in Shanghai, China. Methods: An online training program on the diagnosis and treatment of MPP, guided by Kern's six-step approach, was developed by the Shanghai Pediatric Clinical Quality Control Center. A pre- and post-training survey was conducted using a 20-item self-administered questionnaire to investigate the pediatricians' knowledge of MPP. A linkage mechanism was established to match pretest/posttest questionnaires using personal identifiers. Paired t-tests and McNemar tests were performed to measure the differences, as appropriate, between pre- and post-training groups. A higher survey score indicated better knowledge. Results: There were 289 participants performed pre- and post-tests. The average age of the respondents was 38.7 years (standard deviation: 8.9). Over 80% of the participants were primary (32.5%) and intermediate (47.8%) pediatricians. Those from specialized hospitals accounted for the highest proportion (41.5%). The post-training group achieved significantly higher total scores than the pre-training group (91.3 vs. 67.7, t=22.48, P<0.001), regardless of the professional titles or hospital levels (all P<0.001). The accuracy rates of each question increased significantly in the post-training group (all P<0.001). Conclusions: The online training program effectively enhanced pediatricians' understanding of diagnosing and treating MPP. It is recommended to maintain continuous education and training targeting all healthcare providers.

SARS-CoV-2 Spike Protein 1 Causes Aggregation of α-Synuclein via Microglia-Induced Inflammation and Production of Mitochondrial ROS: Potential Therapeutic Applications of Metformin.

Abnormal aggregation of α-synuclein is the hallmark of neurodegenerative diseases, classified as α-synucleinopathies, primarily occurring sporadically. Their onset is associated with an interaction between genetic susceptibility and environmental factors such as neurotoxins, oxidative stress, inflammation, and viral infections. Recently, evidence has suggested an association between neurological complications in long COVID (sometimes referred to as 'post-acute sequelae of COVID-19') and α-synucleinopathies, but its underlying mechanisms are not completely understood. In this study, we first showed that SARS-CoV-2 Spike protein 1 (S1) induces α-synuclein aggregation associated with activation of microglial cells in the rodent model. In vitro, we demonstrated that S1 increases aggregation of α-synuclein in BE(2)M-17 dopaminergic neurons via BV-2 microglia-mediated inflammatory responses. We also identified that S1 directly affects aggregation of α-synuclein in dopaminergic neurons through increasing mitochondrial ROS, though only under conditions of sufficient α-Syn accumulation. In addition, we observed a synergistic effect between S1 and the neurotoxin MPP+ S1 treatment. Combined with a low dose of MPP+, it boosted α-synuclein aggregation and mitochondrial ROS production compared to S1 or the MPP+ treatment group. Furthermore, we evaluated the therapeutic effects of metformin. The treatment of metformin suppressed the S1-induced inflammatory response and α-synucleinopathy. Our findings demonstrate that S1 promotes α-synucleinopathy via both microglia-mediated inflammation and mitochondrial ROS, and they provide pathological insights, as well as a foundation for the clinical management of α-synucleinopathies and the onset of neurological symptoms after the COVID-19 outbreak.

Fraction of C. d. collilineatus venom containing crotapotin protects PC12 cells against MPP + toxicity by activating the NGF-signaling pathway.

Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. There is no effective treatment for neurodegenerative diseases. Snake venoms are a cocktail of proteins and peptides with great therapeutic potential and might be useful in the treatment of neurodegenerative diseases. Crotapotin is the acid chain of crotoxin, the major component of Crotalus durissus collilineatus venom. PD is characterized by low levels of neurotrophins, and synaptic and axonal degeneration; therefore, neurotrophic compounds might delay the progression of PD. The neurotrophic potential of crotapotin has not been studied yet. Methods: We evaluated the neurotrophic potential of crotapotin in untreated PC12 cells, by assessing the induction of neurite outgrowth. The activation of the NGF signaling pathway was investigated through pharmacological inhibition of its main modulators. Additionally, its neuroprotective and neurorestorative effects were evaluated by assessing neurite outgrowth and cell viability in PC12 cells treated with the dopaminergic neurotoxin MPP+ (1-methyl-4-phenylpyridinium), known to induce Parkinsonism in humans and animal models. Results: Crotapotin induced neuritogenesis in PC12 cells through the NGF-signaling pathway, more specifically, by activating the NGF-selective receptor trkA, and the PI3K/Akt and the MAPK/ERK cascades, which are involved in neuronal survival and differentiation. In addition, crotapotin had no cytotoxic effect and protected PC12 cells against the inhibitory effects of MPP+ on cell viability and differentiation. Conclusion: These findings show, for the first time, that crotapotin has neurotrophic/neuroprotective/neurorestorative potential and might be beneficial in Parkinson's disease. Additional studies are necessary to evaluate the toxicity of crotapotin in other cell models.

Neuroprotective and Neurite Outgrowth Stimulating Effects of New Low-Basicity 5-HT7 Receptor Agonists: In Vitro Study in Human Neuroblastoma SH-SY5Y Cells.

There is some evidence that the serotonin receptor subtype 7 (5-HT7) could be new therapeutic target for neuroprotection. The aim of this study was to compare the neuroprotective and neurite outgrowth potential of new 5-HT7 receptor agonists (AH-494, AGH-238, AGH-194) with 5-CT (5-carboxyamidotryptamine) in human neuroblastoma SH-SY5Y cells. The results revealed that 5-HT7 mRNA expression was significantly higher in retinoic acid (RA)-differentiated cells when compared to undifferentiated ones and it was higher in cell cultured in neuroblastoma experimental medium (DMEM) compared to those placed in neuronal (NB) medium. Furthermore, the safety profile of compounds was favorable for all tested compounds at concentration used for neuroprotection evaluation (up to 1 µM), whereas at higher concentrations (above 10 µM) the one of the tested compounds, AGH-194 appeared to be cytotoxic. While we observed relatively modest protective effects of 5-CT and AH-494 in UN-SH-SY5Y cells cultured in DMEM, in UN-SH-SY5Y cells cultured in NB medium we found a significant reduction of H2O2-evoked cell damage by all tested 5-HT7 agonists. However, 5-HT7-mediated neuroprotection was not associated with inhibition of caspase-3 activity and was not observed in RA-SH-SY5Y cells exposed to H2O2. Furthermore, none of the tested 5-HT7 agonists altered the damage induced by 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenylpyridinium ion (MPP +) and doxorubicin (Dox) in UN- and RA-SH-SY5Y cells cultured in NB. Finally we showed a stimulating effect of AH-494 and AGH-194 on neurite outgrowth. The obtained results provide insight into neuroprotective and neurite outgrowth potential of new 5-HT7 agonists.

A new wide input voltage DC-DC converter for solar PV systems with hybrid MPPT controller.

The present working conventional power generation systems utilization is reducing day by day because of their demerits are more functioning cost, high carbon dioxide emission, more complexity in handling, and required high installation area. So, the current power generation company focuses on Renewable Energy Sources (RES) which are wind, tidal, and solar. Here, the solar power network is utilized for supplying electricity to the electrical vehicle battery charging system. The Solar photovoltaic (PV) modules supply nonlinear power which is not useful for automotive systems. To maximize the supply power of the solar PV system, an Adaptive Step Genetic Algorithm Optimized (ASGAO) Radial Basis Functional Network (RBFN) is utilized for tracking the working point of the solar PV module thereby enhancing the operating efficiency of the overall system. The features of this proposed hybrid Maximum Power Point Tracking (MPPT) controller are quick system dynamic response, easy operation, quick convergence speed, more robustness, and high operating efficiency when equalized with the basic MPPT controllers. The major issue of solar PV modules is low supply voltage which is increased by introducing the wide input voltage DC-DC converter. The merits of this introduced converter are low-level voltage stress on diodes, good quality supply power, high voltage gain, plus low implementation cost. Here, the introduced converter along with the AGAO-RBFN controller is analyzed by selecting the MATLAB/Simulink environment. Also, the proposed converter is tested with the help of a programable DC source.

Intravitreal MPTP drives retinal ganglion cell loss with oral nicotinamide treatment providing robust neuroprotection.

Neurodegenerative diseases have common underlying pathological mechanisms including progressive neuronal dysfunction, axonal and dendritic retraction, and mitochondrial dysfunction resulting in neuronal death. The retina is often affected in common neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Studies have demonstrated that the retina in patients with Parkinson's disease undergoes changes that parallel the dysfunction in the brain. These changes classically include decreased levels of dopamine, accumulation of alpha-synuclein in the brain and retina, and death of dopaminergic nigral neurons and retinal amacrine cells leading to gross neuronal loss. Exploring this disease's retinal phenotype and vision-related symptoms is an important window for elucidating its pathophysiology and progression, and identifying novel ways to diagnose and treat Parkinson's disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is commonly used to model Parkinson's disease in animal models. MPTP is a neurotoxin converted to its toxic form by astrocytes, transported to neurons through the dopamine transporter, where it causes mitochondrial Complex I inhibition and neuron degeneration. Systemic administration of MPTP induces retinal changes in different animal models. In this study, we assessed the effects of MPTP on the retina directly via intravitreal injection in mice (5 mg/mL and 50 mg/mL to 7, 14 and 21 days post-injection). MPTP treatment induced the reduction of retinal ganglion cells-a sensitive neuron in the retina-at all time points investigated. This occurred without a concomitant loss of dopaminergic amacrine cells or neuroinflammation at any of the time points or concentrations tested. The observed neurodegeneration which initially affected retinal ganglion cells indicated that this method of MPTP administration could yield a fast and straightforward model of retinal ganglion cell neurodegeneration. To assess whether this model could be amenable to neuroprotection, mice were treated orally with nicotinamide (a nicotinamide adenine dinucleotide precursor) which has been demonstrated to be neuroprotective in several retinal ganglion cell injury models. Nicotinamide was strongly protective following intravitreal MPTP administration, further supporting intravitreal MPTP use as a model of retinal ganglion cell injury. As such, this model could be utilized for testing neuroprotective treatments in the context of Parkinson's disease and retinal ganglion cell injury.

A comprehensive performance analysis of advanced hybrid MPPT controllers for fuel cell systems.

The present power generation corporations are working on Renewable Power Systems (RPS) for supplying electrical power to the automotive power industries. There are several categories of RPSs available in the atmosphere. Among all of the RPSs, the most general power network used for Electric Vehicles (EVs) is hydrogen fuel which is available in nature. The H2 fuel is fed to the Proton Exchange Membrane Fuel Stack (PEMFS) for producing electricity for the EV stations. The advantages of this selected fuel system are more power conversion efficiency, environmentally friendly, low carbon emissions, more power density, less starting time, plus able to work at very low-temperature values. However, this fuel stack faces the issue of a nonlinear power density curve. Due to this nonlinear power supply from the fuel stack, the functioning point of the overall network changes from one position of the I-V curve to another position. So, the peak voltage extraction from the fuel stack is not possible. In this article, there are various metaheuristic optimization-based Maximum Power Point Tracking (MPPT) methodologies are studied along with the conventional methods for obtaining the Maximum Power Point (MPP) position of the PEMFS. From the simulative investigation, the Continuous Different Slope Value-based Cuckoo Search Method (CDSV with CSM) provides better efficiency with more output power. Also, for all the MPPT methods comprehensive analysis has been made by utilizing the simulation results.

Evaluation of Cotton Fleahopper (Pseudatomoscelis seriatus (Reuter)) Feeding on Mpp51Aa2-Traited Cotton Utilizing Electrical Penetration Graph (EPG) Waveforms.

Prior to the recent implementation of the Mpp51Aa2 pesticidal protein (ThryvOn), transgenic cotton cultivars have historically offered no control of the cotton fleahopper (Pseudatomocelis seriatus (Reuter)). To evaluate the feeding behavior of cotton fleahoppers on ThryvOn cotton, electropenetrography (EPG) using a Giga-8 DC instrument was used to monitor the probing activity of fourth- and fifth-instar cotton fleahopper nymphs on both ThryvOn and non-ThryvOn cotton squares. Nymphs were individually placed on an excised cotton square for 8 h of EPG recording, after which resulting waveforms were classified as non-probing, cell rupturing, or ingestion. Although there were significantly more cell rupturing events per insect on ThryvOn (mean ± SEM, 14.8 ± 1.7) than on non-ThryvOn squares (mean ± SEM, 10.3 ± 1.6), there was no difference attributable to ThryvOn in the average number of ingestion events per insect. However, the average duration of ingestion events was significantly shorter on squares with ThryvOn (mean ± SEM, 509 ± 148 s) than on squares without (mean ± SEM, 914 ± 135 s). This suggests that cotton fleahoppers continued to probe despite their inability to sustain ingestion. These results provide conclusive evidence that the Mpp51Aa2 pesticidal protein affects the feeding behavior of cotton fleahopper nymphs.

Polyadenylated versions of small non-coding RNAs in Saccharomyces cerevisiae are degraded by Rrp6p/Rrp47p independent of the core nuclear exosome.

In Saccharomyces cerevisiae, polyadenylated forms of mature (and not precursor) small non-coding RNAs (sncRNAs) those fail to undergo proper 3'-end maturation are subject to an active degradation by Rrp6p and Rrp47p, which does not require the involvement of core exosome and TRAMP components. In agreement with this finding, Rrp6p/Rrp47p is demonstrated to exist as an exosome-independent complex, which preferentially associates with mature polyadenylated forms of these sncRNAs. Consistent with this observation, a C-terminally truncated version of Rrp6p (Rrp6p-ΔC2) lacking physical association with the core nuclear exosome supports their decay just like its full-length version. Polyadenylation is catalyzed by both the canonical and non-canonical poly(A) polymerases, Pap1p and Trf4p. Analysis of the polyadenylation profiles in WT and rrp6-Δ strains revealed that the majority of the polyadenylation sites correspond to either one to three nucleotides upstream or downstream of their mature ends and their poly(A) tails ranges from 10-15 adenylate residues. Most interestingly, the accumulated polyadenylated snRNAs are functional in the rrp6-Δ strain and are assembled into spliceosomes. Thus, Rrp6p-Rrp47p defines a core nuclear exosome-independent novel RNA turnover system in baker's yeast targeting imperfectly processed polyadenylated sncRNAs that accumulate in the absence of Rrp6p.

A novel development of a new single switch inductor coupled DC-DC converter for PV system with two-leg inverter.

From the power generation history, the nonrenewable power sources utilization is falling extremely because of their demerits are high atmospheric pollution, more expensive, more catchment area for development, high fossil fuel transportation cost, less flexibility, and reliability. So, the sunlight systems are utilized in this work for feeding the power to the central grid. On the earth, the sunlight energy availability is more and it is more flexible for the installation. However, the sunlight photovoltaic (PV) module's power production is very low. To improve the power generation of the PV network, a modified slider maximum power point tracking (MPPT) controller is proposed in the first objective and it is interfaced with the sunlight system for capturing more sunlight insolation thereby moving the functioning point of the solar system from local MPP place to required global MPP place. The features of this sliding controller are continuous peak power production, easy development, less power dissipation losses, plus good dynamic system response. In the second objective, the available voltage of the PV is low which improved from low level to high level by utilizing the Wide voltage supply-inductor coupled converter. The development of this circuit needed very less inductive, plus capacitive components. Also, it is developed by selecting a single switch. As a result, the entire network power production cost is reduced. In the third objective, a two-leg inverter is proposed for the transformation of the DC voltage supply into three-phase powers. The MATLAB/Simulink tool is used to investigate the overall system.

A novel design and analysis of hybrid fuzzy logic MPPT controller for solar PV system under partial shading conditions.

Renewable energy resources are more useful when associated with the thermal power generation network because of their high accessibility in the environment, good system response, easy manufacturing, plus high scalable. So, the present research is going on solar power to reduce consumer grid dependency. The running of the PV network is quite easier, plus less human sources are involved. However, the solar modules' power generation is nonlinear fashion. So, the collection of peak power from the sunlight-dependent systems is a highly challenging task. In this article, a Modified Differential Step Grey Wolf Optimization with Adaptive Fuzzy Logic Controller (MDSGWO with FLC) is developed for collecting the maximum power from renewable energy resources under diverse Partial Shading Conditions (PSCs). The introduced method comprehensive analysis has been done along with the other recently existing MPPT methods in terms of convergence speed, MPP tracking accuracy, operating efficiency of the introduced method, functioning duty value of the DC-DC boost power converter, dependence of MPPT on sunlight system, total number of sensing devices are needed, plus peak power extraction from the proposed system. Here, the sunlight power generation cost is more to limit this issue, a power converter is selected in the second objective to develop the voltage source capability of the PV network. The overall PV-interfaced power converter network is examined by utilizing the MATLAB environment.

Cotton plants overexpressing the Bacillus thuringiensis Cry23Aa and Cry37Aa binary-like toxins exhibit high resistance to the cotton boll weevil (Anthonomus grandis).

The cotton boll weevil (CBW, Anthonomus grandis) stands as one of the most significant threats to cotton crops (Gossypium hirsutum). Despite substantial efforts, the development of a commercially viable transgenic cotton event for effective open-field control of CBW has remained elusive. This study describes a detailed characterization of the insecticidal toxins Cry23Aa and Cry37Aa against CBW. Our findings reveal that CBW larvae fed on artificial diets supplemented exclusively with Cry23Aa decreased larval survival by roughly by 69%, while supplementation with Cry37Aa alone displayed no statistical difference compared to the control. However, the combined provision of both toxins in the artificial diet led to mortality rates approaching 100% among CBW larvae (LC50 equal to 0.26 PPM). Additionally, we engineered transgenic cotton plants by introducing cry23Aa and cry37Aa genes under control of the flower bud-specific pGhFS4 and pGhFS1 promoters, respectively. Seven transgenic cotton events expressing high levels of Cry23Aa and Cry37Aa toxins in flower buds were selected for greenhouse bioassays, and the mortality rate of CBW larvae feeding on their T0 and T1 generations ranged from 75% to 100%. Our in silico analyses unveiled that Cry23Aa displays all the hallmark characteristics of ß-pore-forming toxins (ß-PFTs) that bind to sugar moieties in glycoproteins. Intriguingly, we also discovered a distinctive zinc-binding site within Cry23Aa, which appears to be involved in protein-protein interactions. Finally, we discuss the major structural features of Cry23Aa that likely play a role in the toxin's mechanism of action. In view of the low LC50 for CBW larvae and the significant accumulation of these toxins in the flower buds of both T0 and T1 plants, we anticipate that through successive generations of these transgenic lines, cotton plants engineered to overexpress cry23Aa and cry37Aa hold promise for effectively managing CBW infestations in cotton crops.

Synaptic vesicle glycoprotein 2C enhances vesicular storage of dopamine and counters dopaminergic toxicity.

Dopaminergic neurons of the substantia nigra exist in a persistent state of vulnerability resulting from high baseline oxidative stress, high-energy demand, and broad unmyelinated axonal arborisations. Impairments in the storage of dopamine compound this stress because of cytosolic reactions that transform the vital neurotransmitter into an endogenous neurotoxicant, and this toxicity is thought to contribute to the dopamine neuron degeneration that occurs Parkinson's disease. We have previously identified synaptic vesicle glycoprotein 2C (SV2C) as a modifier of vesicular dopamine function, demonstrating that genetic ablation of SV2C in mice results in decreased dopamine content and evoked dopamine release in the striatum. Here, we adapted a previously published in vitro assay utilising false fluorescent neurotransmitter 206 (FFN206) to visualise how SV2C regulates vesicular dopamine dynamics and determined that SV2C promotes the uptake and retention of FFN206 within vesicles. In addition, we present data indicating that SV2C enhances the retention of dopamine in the vesicular compartment with radiolabelled dopamine in vesicles isolated from immortalised cells and from mouse brain. Further, we demonstrate that SV2C enhances the ability of vesicles to store the neurotoxicant 1-methyl-4-phenylpyridinium (MPP+) and that genetic ablation of SV2C results in enhanced 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced vulnerability in mice. Together, these findings suggest that SV2C functions to enhance vesicular storage of dopamine and neurotoxicants and helps maintain the integrity of dopaminergic neurons.

Effects of polypropylene microplastics on carbon dioxide dynamics in intertidal mangrove sediments.

Microplastics (MPs) in soil can influence CO2 dynamics by altering organic carbon (OC) and microbial composition. Nevertheless, the fluctuation of CO2 response attributed to MPs in mangrove sediments is unclear. This study explores the impact of micro-sized polypropylene (mPP) particles on the carbon dynamics of intertidal mangrove sediments. In the high-tide level sediment, after 28 days, the cumulative CO2 levels for varying mPP dosages were as follows: 496.86 ± 2.07, 430.38 ± 3.84 and 447.09 ± 1.72 mg kg-1 for 0.1%, 1% and 10% (w/w) mPP, respectively. The CO2 emissions were found to be increased with a 0.1% (w/w) mPP level and decreased with 1% and 10% (w/w) mPP at high-tide level sediment, suggesting a tide level-specific dose dependence of the CO2 emission pattern in mangrove sediments. Overall, results indicated that the presence of mPP in mangrove sediments would potentially affect intertidal total CO2 storage under given experimental conditions.

Targeting PERK-ATF4-P21 axis enhances the sensitivity of osteosarcoma HOS cells to Mppα-PDT.

Osteosarcoma (OS) is the most prevalent type of malignant bone tumor in adolescents. The overall survival of OS patients has reached a plateau recently. Thus, there is an urgent need to develop approaches to improve the sensitivity of OS to therapies. Pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPα-PDT) is a new type of tumor therapy, and elucidating its mechanism is helpful to improve its anti-tumor efficacy. Here, we investigated how PERK signaling promotes the human OS (HOS) cell survival induced by MPPα-PDT, as overcoming this may enhance sensitivity to MPPα-PDT. We found that MPPα-PDT combined with PERK inhibitor GSK2656157 enhanced HOS cell apoptosis by suppressing autophagy and p21. Autophagy inhibition and p21 depletion enhanced cell death, indicating pro-survival effects in MPPα-PDT. Notably, p21 was found to be an effector of the PERK-Atf4 pathway, which could positively regulate autophagy mediated by MPPα-PDT. In conclusion, we found that the combination of MPPα-PDT and GSK2656157 enhanced apoptosis in HOS cells by inhibiting autophagy. Mechanistically, this autophagy is p21-dependent and can be suppressed by GSK2656157, thereby enhancing sensitivity to MPPα-PDT.

Tumor Targeting via siRNA-COG3 to Suppress Tumor Progression in Mice and Inhibit Cancer Metastasis and Angiogenesis in Ovarian Cancer Cell Lines.

BACKGROUND: The COG complex is implicated in the tethering of retrograde intra-Golgi vesicles, which involves vesicular tethering and SNAREs. SNARE complexes mediate the inva-sion and metastasis of cancer cells through MMPs which activate growth factors for ECM frag-ments by binding to integrin receptors. Increasing MMPs is in line with YKL40 since YKL40 is linked to promoting angiogenesis through VEGF and can increase ovarian cancer (OC) resistance to chemotropic and cell migration. OBJECTIVE: The aim of this study is an assessment of siRNA-COG3 on proliferation, invasion, and apoptosis of OC cells. In addition, siRNA-COG3 may prevent the growth of OC cancer in mice with tumors. METHODS: Primary OC cell lines will be treated with siRNA-COG3 to assay YKL40 and identified angiogenesis by Tube-like structure formation in HOMECs. The Golgi morphology was analyzed using Immunofluorescence microscopy. Furthermore, the effects of siRNA-COG3 on the prolifer-ation and apoptosis of cells were evaluated using MTT and TUNEL assays. Clones of the HOSEpiC OC cell line were subcutaneously implanted in FVB/N mice. Mice were treated after two weeks of injection of cells using siRNA-COG3. Tumor development suppression was detected by D-luciferin. RT-PCR and western blotting analyses were applied to determine COG3, MT1-MMP, SNAP23, and YKL40 expression to investigate the effects of COG3 gene knockdown. RESULTS: siRNA-COG3 exhibited a substantial effect in suppressing tumor growth in mice. It dra-matically reduced OC cell proliferation and triggered apoptosis (all p < 0.01). Inhibition of COG3, YKL-40, and MT1-MPP led to suppression of angiogenesis and reduction of microvessel density through SNAP23 in OC cells. CONCLUSION: Overall, by knockdown of the COG3 gene, MT1-MMP and YKL40 were dropped, leading to suppressed angiogenesis along with decreasing migration and proliferation. SiRNA-COG3 may be an ideal agent to consider for clinical trial assessment therapy for OC, especially when an antiangiogenic SNAR-pathway targeting drug.

A case of a childhood onset developmental encephalopathy with a novel de novo truncating variant in the Membrane Protein Palmitoylated 5 (MPP5) gene.

BACKGROUND: Membrane Protein Palmitoylated 5 (MPP5) is a highly conserved apical complex protein, essential for cell polarity. Defects in neuronal cell polarity are associated with neurologic disorders. Only three patients with heterozygous MPP5 de novo variants have been reported so far, with global developmental delay, behavioral changes and in only one case epileptic seizures. OBJECTIVE: To describe a new patient with a novel truncating de novo mutation in MPP5 and to characterize in detail the epileptic phenotype and electroencephalographic features of the encephalopathy. METHODS: We identified a novel truncating de novo mutation in MPP5 in a 44 year old patient by exome sequencing (p.Ser498Phefs*15). We retrospectively analyzed his clinical and instrumental data along a thirty-year follow up. RESULT: Our patient presents with generalized tonic-clonic seizures, myoclonic and clonic seizures, non-epileptic myoclonus, tremor, severe intellectual disability, mild face dysmorphic traits, and psychosis. DISCUSSION AND CONCLUSION: We present a case of a childhood onset developmental encephalopathy with a likely-pathogenic variant in the MPP5 gene.. This represents the first complete description of the epileptic syndrome associated with the MPP5 gene.

In vitro caries-preventive effect of a mineralization-promoting peptide combined with fluoride gel on sound primary teeth.

BACKGROUND: Mineralization-promoting peptide-3 (MPP3) is a new biomimetic remineralization agent. AIM: To assess the remineralization efficiency of MPP3, either alone or in combination with fluoride gel. DESIGN: The samples were divided into four groups: control, 1.23% fluoride gel, 10% MPP3 gel, and 1.23% fluoride gel + 10% MPP3. Following the application of remineralization agents (4 min), the samples remained in a pH-cycling model (37°C, 4 weeks). Microhardness, microcomputed tomography (micro-CT), polarized light microscopy (PLM), and field emission scanning electron microscopy (FE-SEM) analysis were conducted. RM-ANOVA, one-way ANOVA, and intraclass correlation coefficient (ICC) were used for statistical analysis, and a significance level of p < .05 was employed. RESULTS: Mineralization-promoting peptide 3 and fluoride gel + MPP3 increased the microhardness of the enamel compared with initial values in each group (p < .05). Mineralization-promoting peptide 3 successfully maintained the mineral density of enamel, although the cariogenic pH-cycling and PLM results indicated that the lesion depth (µm) was significantly lower in the fluoride gel + MPP3 group (27.0336 ± 12.53650) than in the control group (37.3907 ± 12.76002, p < .05). CONCLUSION: The combined use of MPP3 with fluoride gel enhanced the caries-protective and mineralization-promoting effects of fluoride. Mineralization-promoting peptide 3 may be a potential agent that can be employed to improve the physical properties of enamel.

EGFR co-mutation is associated with the risk of recurrence in invasive lung adenocarcinoma with the micropapillary component.

BACKGROUND: Invasive lung adenocarcinoma (LUAD) patients with the micropapillary (MPP) component tend to have extremely poor prognosis. To optimize clinical outcomes, a better understanding of specific concurrent gene alterations and their impact on the prognosis of patients with the MPP component is necessary. METHOD: A total of 621 Chinese patients with surgically resected invasive LUAD who underwent genetic testing for lung cancer were enrolled in this retrospective study. The genomic profiling of major lung cancer-related genes based on next-generation sequencing (NGS) was carried out on formalin-fixed paraffin-embedded tumor samples. RESULT: Among 621 patients with invasive LUAD, 154 (24.8%, 154/621) had the MPP component. We found that PIK3CA (4.5% vs 1.3%), KRAS (9.1% vs 4.7%), and ROS1 (2.6% vs 0.4%) were more frequent in patients with the MPP component than those without the MPP component (P < 0.05). The co-mutation occurred in 66 patients (10.6%, 66/621), of which 19 patients with the MPP component. Most of them were EGFR co-mutations (89.5%, 17/19), including EGFR and PIK3CA, EGFR and ERBB2, and other types. Patients with the MPP component who harbored EGFR co-mutations showed significantly worse recurrence-free survival (RFS) than single EGFR mutation (median RFS 20.1 vs 30.5 months; hazard ratio [HR]: 8.008; 95% confidence interval [CI]: 1.322-48.508). CONCLUSIONS: Patients with the MPP component harbored the co-mutation of driver genes had a higher risk of recurrence after surgery, especially in patients with EGFR co-mutation. EGFR co-mutation was a significant prognostic factor for RFS in patients with the MPP component.

Unveiling the regulatory of miR-101-3p on ZNF746 in a Parkinson's disease cell model: Implications for therapeutic targeting.

In this study, we explored the regulatory role of microRNA miR-101-3p on the zinc finger protein 746 (ZNF746), also known as PARIS, which is implicated in both sporadic and familial forms of Parkinson's disease. In a Parkinson's disease cell model, utilizing SH-SY5Y cells treated with 1-methyl-4-phenylpyridine (MPP+), we observed that miR-101-3p was downregulated, while ZNF746 was upregulated. To investigate the direct impact of miR-101-3p on ZNF746, our team conducted overexpression experiments, successfully reversing ZNF746's expression at both the mRNA and protein levels, as confirmed through quantitative PCR and western blotting. We also performed luciferase assays, providing compelling evidence that ZNF746 is a direct target of miR-101-3p. Additionally, we noted that miR-101-3p overexpression resulted in increased expression of PGC1α, a gene targeted by ZNF746. Functionally, we assessed the implications of miR-101-3p overexpression through MTS assays and flow cytometry, revealing significant promotion of cell viability, inhibition of ROS production, and reduced apoptosis in the Parkinson's disease cell model. In conclusion, this study highlights the role of miR-101-3p in regulating ZNF746 expression and suggests its potential as a therapeutic target for Parkinson's disease. These findings provide valuable molecular insights that could pave the way for innovative treatment strategies in combating this debilitating neurodegenerative disorder.