Optimal use of β-lactams in neonates: machine learning-based clinical decision support system.

Background: Accurate prediction of the optimal dose for β-lactam antibiotics in neonatal sepsis is challenging. We aimed to evaluate whether a reliable clinical decision support system (CDSS) based on machine learning (ML) can assist clinicians in making optimal dose selections.

Methods: Five β-lactam antibiotics (amoxicillin, ceftazidime, cefotaxime, meropenem and latamoxef), commonly used to treat neonatal sepsis, were selected.

The STING inhibitor C-176 attenuates MPTP-induced neuroinflammation and neurodegeneration in mouse parkinsonian models.

Recent emerging evidence reveals that cGAS-STING-mediated Type I interferon (IFN) signaling axis takes part in the microglial-associated neuroinflammation. However, the potential role of pharmacological inhibition of STING on neuroinflammation and dopaminergic neurodegeneration remains unknown. In the present study, we investigated whether pharmacological inhibition of STING attenuates neuroinflammation and neurodegeneration in experimental models of Parkinson's disease.

[Emergency Management of Medical Equipment in Designated Hospitals for Public Health Emergencies].

Medical supply is a key resource for responding to public health emergencies and maintaining people's lives and health. As the medical equipment management department, the medical devices department is mainly responsible for the procurement, supply, technical support, management and coordination of medical equipment and medical consumables, playing an important role in epidemic prevention and control. Through the analysis of the expansion cases of designated hospitals, the experience of emergency management of medical equipment has been accumulated, which has strong practicability and replicability.

Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson's disease model.

Microglia-mediated neuroinflammation and mitochondrial dysfunction play critical role in the pathogenic process of Parkinson's disease (PD). Mitophagy plays central role in mitochondrial quality control. Hence, regulation of microglial activation through mitophagy could be a valuable strategy in controlling microglia-mediated neurodegeneration and neuroinflammation.

Urolithin A protects dopaminergic neurons in experimental models of Parkinson's disease by promoting mitochondrial biogenesis through the SIRT1/PGC-1α signaling pathway.

Mitochondrial dysfunction contributes to the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). Therapeutic strategies targeting mitochondrial dysfunction hold considerable promise for the treatment of PD. Recent reports have highlighted the protective role of urolithin A (UA), a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries and walnuts, in several neurological disorders including Alzheimer's disease and ischemic stroke.

Design, synthesis and biological evaluation of dual HDAC and VEGFR inhibitors as multitargeted anticancer agents.

Herein, a novel series of dual histone deacetylase (HDAC) and vascular endothelial growth factor receptor (VEGFR) inhibitors were designed, synthesized and biologically evaluated based on previously reported pazopanib-based HDAC and VEGFR dual inhibitors. Most target compounds showed significant HDAC1, HDAC6 and VEGFR2 inhibition, which contributed to their potent antiproliferative activities against multiple cancer cell lines and significant antiangiogenic potencies in both human umbilical vein endothelial cell (HUVEC) tube formation assays and rat thoracic aorta ring assays. Further HDAC selectivity evaluations indicated that hydroxamic acids 5 and 9e possessed HDAC isoform selectivity profiles similar to that of the approved HDAC inhibitor suberoylanilide hydroxamic acid(SAHA), while hydrazide12 presented an HDAC isoform selectivity profilesimilar to that of the clinical HDAC inhibitor MS-275.

In vitro and in vivo anti-inflammatory effect of Zaluzanin D isolated from Achillea acuminate.

The present study was investigated to verify anti-inflammatory and immune regulation effect of Zaluzanin D on LPS-induced macrophages and acute lung injury. NR8383 macrophages were pre-treated with Zaluzanin D and stimulated by LPS. Zaluzanin D reduced the production of nitric oxide in NR8383 macrophages and decreased the secretions of inflammatory cytokines.

Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance.

Background: The development of paclitaxel (PTX) resistance seriously restricts its clinical efficacy. An attractive option for combating resistance is inhibiting the expression of P-glycoprotein (P-gp) in tumor cells. We have reported that flavokawain A (FKA) inhibited P-gp protein expression in PTX-resistant A549 (A549/T) cells, indicating that FKA combined with PTX may reverse PTX resistance.

Purification, structural characterization and in vivo immunoregulatory activity of a novel polysaccharide from Polygonatum sibiricum.

The purpose of this study was to study polysaccharides isolated from Polygonatum sibiricum to establish the structure-activity relationships of the active substances and to discover the optimal fraction for further development and application. Four polysaccharides fractions (PSP1, PSP2, PSP3 and PSP4) from P. sibiricum were obtained by DEAE-Sepharose Fast Flow ion-exchange chromatography.

Polysaccharides from Delar. ex Redoute induce an immune response in the RAW264.7 cell line an NF-κB/MAPK pathway.

The aim of this study was to examine the effect of polysaccharides from (PSP) on RAW 264.7 cells together with the underlying signaling pathways. Water-soluble polysaccharides were extracted from and the immunological activity/mechanism was explored in depth in RAW 264.

Models Matter, So Does Training: An Empirical Study of CNNs for Optical Flow Estimation.

We investigate two crucial and closely-related aspects of CNNs for optical flow estimation: models and training. First, we design a compact but effective CNN model, called PWC-Net, according to simple and well-established principles: pyramidal processing, warping, and cost volume processing. PWC-Net is 17 times smaller in size, 2 times faster in inference, and 11 percent more accurate on Sintel final than the recent FlowNet2 model.

Qualitative and quantitative analysis of Yifei Tongluo granules to identify main bioactive components using LC-DAD/MS and pharmacokinetic studies.

A standard fingerprint containing twelve common peaks was constructed from ten batches of Yifei Tongluo granules to evaluate batch-to-batch consistency by using HPLC-DAD. Additionally, the corresponding medicinal material attributes of these chemical constituents were analyzed according to the data acquired from the HPLC method and the identification was further carried out using the LC-MS/MS method. Comparing the retention time or accurate mass with previous studies or standards, the common components were tentatively identified in 50 min for ten batches of samples.

Acetyl-11-keto-β-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus suppressing chemoresistant stem cell-like properties.

Acquired docetaxel-resistance of prostate cancer (PCa) remains a clinical obstacle due to the lack of effective therapies. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic triterpenic acid isolated from the fragrant gum resin of the Boswellia serrata tree, which has shown intriguing antitumor activity against human cell lines established from PCa, colon cancer, malignant glioma, and leukemia. In this study, we examined the effects of AKBA against docetaxel-resistant PCa in vitro and in vivo as well as its anticancer mechanisms.

Suppression of the NF‑κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute.

Colorectal cancer (CRC) is a major cause of mortality and morbidity. Chronic inflammation is closely associated with the development, progression and prognosis of the majority of intestinal malignancies. In recent years, targeting the nuclear factor (NF)‑κB signaling pathway for CRC therapy has become an attractive strategy.

Acetylpuerarin protects against OGD-induced cell injury in BV2 microglia by inhibiting HMGB1 release.

High mobility group box 1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic injury, initiates inflammatory response and aggravates brain tissue damage. Acetylpuerarin (AP), an acetylated derivative of puerarin, was reported to protect against cerebrovascular ischemia-reperfusion injury in rats through anti-inflammation. In the present study, we aim to investigate whether AP inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated BV2 microglia.

Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells.

Retigeric acid B (RAB), a natural compound isolated from lichen, has been demonstrated to inhibit cell growth and promote apoptosis in prostate cancer (PCa) cells. The present study evaluated the function of RAB combined with clinical chemotherapeutic drugs in PCa cell lines by MTT assay, reverse transcription quantitative polymerase chain reaction and western blot analysis, and identified that RAB at low doses produced significant synergistic cytotoxicity in combination with cisplatin (CDDP); however, no marked synergism between RAB and the other chemotherapeutics was observed. Additional studies revealed that RAB exerted an inhibitory effect on DNA damage repair pathways, including the nucleotide excision repair and mismatch repair pathways, which are involved in the sensitivity to CDDP-based chemotherapy, as suggested by the significantly downregulated expression of certain associated repair proteins.

Deblurring Images via Dark Channel Prior.

We present an effective blind image deblurring algorithm based on the dark channel prior. The motivation of this work is an interesting observation that the dark channel of blurred images is less sparse. While most patches in a clean image contain some dark pixels, this is not the case when they are averaged with neighboring ones by motion blur.

Strategies to release doxorubicin from doxorubicin delivery vehicles.

Doxorubicin (DOX) is one of the most effective cytotoxic anticancer drugs and has been successfully applied in clinics to treat haematological malignancies and a broad range of solid tumours. However, the clinical applications of DOX have long been limited due to severe dose-dependent toxicities. Recent advances in the development of DOX delivery vehicles have addressed some of the non-specific toxicity challenges associated with DOX.

Paeonol alleviates epirubicin-induced renal injury in mice by regulating Nrf2 and NF-κB pathways.

Renal injury is a dose-dependent side effect of epirubicin that limits its clinical application in the field of tumor chemotherapy. Paeonol is an active ingredient with a variety of biological activities, including the prevention of multiple antineoplastic-induced toxicities. In the present study, we assessed the renoprotective effect of paeonol on epirubicin-induced nephrotoxicity and investigated the underlying mechanism.

Enhanced antitumor activity and attenuated cardiotoxicity of Epirubicin combined with Paeonol against breast cancer.

Epirubicin is widely used for the therapy of various breast cancers. However, it has serious adverse side effects, particularly cardiotoxicity, which can cause irreversible damage in patients. Paeonol, an active component from Moutan Cortex, enhances antitumor activity of antineoplastics and reduces toxicities induced by chemotherapeutics.

Reversal of the multidrug resistance of human ileocecal adenocarcinoma cells by acetyl-11-keto-β-boswellic acid via downregulation of P-glycoprotein signals.

Multidrug resistance (MDR) represents a clinical obstacle to cancer chemotherapy since it causes cancer recurrence and metastasis. Acetyl-11-keto-β-boswellic acid (AKBA), an active ingredient derived from the plant Boswellia serrata, has been found to inhibit the growth of a wide variety of tumor cells, including glioma, colorectal cancer, leukemia, human melanoma, hepatocellular carcinoma, and prostate cancer cells. However, the actions of AKBA in multidrug-resistant cancer cells have not been fully elucidated.

Bile salt liposomes for enhanced lymphatic transport and oral bioavailability of paclitaxel.

Paclitaxel (PTX), a BCS class IV drug that is characterized by its poor solubility and is a substrate for P-glycoprotein, is one of the most widely used antineoplastic agents. However, oral administration of PTX for chemotherapy is highly challenging. The aim of this study was to develop bile-salt liposomes (BS-Lips) to enhance the absorption of PTX and thus improve its therapeutic outcome.

Enhanced oral bioavailability of acetylpuerarin by poly(lactide-co-glycolide) nanoparticles optimized using uniform design combined with response surface methodology.

Acetylpuerarin (AP), an acetylated derivative of puerarin, shows brain-protective effects in animals. However, AP has low oral bioavailability because of its poor water solubility. The objective of this study was to design and develop poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) to enhance the oral bioavailability of AP.

Multifunctional pH-Responsive Folate Receptor Mediated Polymer Nanoparticles for Drug Delivery.

Multifunctional pH-responsive folate receptor mediated targeted polymer nanoparticles (TPNps) were developed for docetaxel (DTX) delivery based on poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)poly (β-amino ester) (P123-PAE) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)-folate (P123-FA) copolymers. The DTX was loaded into the TPNps with a decent drug loading content of 15.02 ± 0.