Electroacupuncture Activated Impaired Brain Areas and Improved Mental Status and Sleep Quality in Primary Insomnia Patients.

Objective: This study aimed to investigate the specific neurological mechanisms underlying the effects of electroacupuncture at Shenmen (Heart 7) with Neiguan (Pericardium 6) acupoints in patients with primary insomnia (PI). We sought to understand these mechanisms by comparing changes in areaal homogeneity (ReHo) before and after treatment in PI patients and healthy controls (HC). Methods: Between November 2019 and November 2021, we recruited 17 primary insomnia patients (PI group) and 20 matched healthy controls (HC group) as study subjects from Zhaoqing First People's Hospital. Before electroacupuncture treatment, all participants completed the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) assessments. Resting-state magnetic resonance imaging (MRI) scans were conducted before and after two sessions of electroacupuncture at Shenmen and Neiguan acupoints. Results: Before treatment, primary insomnia patients showed higher PSQI (χ2=1.964; P = .017), HAMA (χ2=2.016; P = .027), and HAMD scores (χ2=2.367; P = .013) compared to healthy controls, and increased ReHo values were observed in the left amygdala, bilateral middle temporal gyrus, and left posterior cingulate gyrus in PI patients, while decreased ReHo values were found in the left posterior cingulate gyrus, right middle frontal gyrus, and right precuneus. After treatment, ReHo values increased in the left superior frontal gyrus, right parahippocampal gyrus, and right cingulate gyrus, while they decreased in the left amygdala and right angular gyrus. Primary insomnia disrupts brain areas in the default network, salience network, and parts of the affective cognitive network. Conclusion: Electroacupuncture at Shenmen and Neiguan acupoints partially activated impaired brain areas in patients with primary insomnia, leading to improvements in mental status and sleep quality. This offers a novel perspective for the clinical treatment of primary insomnia.

Monomer and Oligomer Transition of Zinc Phthalocyanine Is Key for Photobleaching in Photodynamic Therapy.

Photodynamic therapy (PDT) is recognized as a powerful method to inactivate cells. However, the photosensitizer (PS), a key component of PDT, has suffered from undesired photobleaching. Photobleaching reduces reactive oxygen species (ROS) yields, leading to the compromise of and even the loss of the photodynamic effect of the PS. Therefore, much effort has been devoted to minimizing photobleaching in order to ensure that there is no loss of photodynamic efficacy. Here, we report that a type of PS aggregate showed neither photobleaching nor photodynamic action. Upon direct contact with bacteria, the PS aggregate was found to fall apart into PS monomers and thus possessed photodynamic inactivation against bacteria. Interestingly, the disassembly of the bound PS aggregate in the presence of bacteria was intensified by illumination, generating more PS monomers and leading to an enhanced antibacterial photodynamic effect. This demonstrated that on a bacterial surface, the PS aggregate photo-inactivated bacteria via PS monomer during irradiation, where the photodynamic efficiency was retained without photobleaching. Further mechanistic studies showed that PS monomers disrupted bacterial membranes and affected the expression of genes related to cell wall synthesis, bacterial membrane integrity, and oxidative stress. The results obtained here are applicable to other types of PSs in PDT.

Cyclometalated Ru(II)-isoquinoline complexes overcome cisplatin resistance of A549/DDP cells by downregulation of Nrf2 via Akt/GSK-3ß/Fyn pathway.

Both ruthenium (Ru) and isoquinoline (IQ) compounds are regarded as potential anticancer drug candidates. Here, we report the synthesis and characterization of three novel cyclometalated Ru(II)-isoquinoline complexes: RuIQ-3, RuIQ-4, and RuIQ-5, and evaluation of their in vitro cytotoxicities against a panel of cell lines including A549/DDP, a cisplatin-resistant human lung cancer cell line. A549/DDP 3D multicellular tumor spheroids (MCTSs) were also used to detect the drug resistance reversal effect of Ru(II)-IQ complexes. Our results indicated that the cytotoxic activities against cancer cells of Ru(II)-IQ complexes, especially RuIQ-5, were superior compared with cisplatin. In addition, RuIQ-5 exhibited low toxicity towards both normal HBE cells in vitro and zebrafish embryos in vivo. Further investigation on cellular mechanism of action indicated that after absorption by A549/DDP cells, RuIQ-5 was mainly distributed in the nucleus, which is different from cisplatin. Besides, RuIQ-5 could induce apoptosis through mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, ROS-mediated DNA damage, and cycle arrest at both S and G2/M phases. Moreover, RuIQ-5 could inhibit the overexpression of Nrf2 through regulation of Akt/GSK-3ß/Fyn signaling pathway and hindering the nuclear translocation of Nrf2. Based on these findings, we firmly believe that the studied Ru(II)-IQ complexes hold great promise as anticancer therapeutics with high effectiveness and low toxicity.

Environmentally relevant concentrations of microplastics modulated the immune response and swimming activity, and impaired the development of marine medaka Oryzias melastigma larvae.

Microplastics (MPs), due to their impacts on the ecosystem and their integration into the food web either through trophic transfer or ingestion directly from the ambient environment, are an emerging class of environmental contaminants posing a great threat to marine organisms. Most reports on the toxic effects of MPs exclusively focus on bioaccumulation, oxidative stress, pathological damage, and metabolic disturbance in fish. However, the collected information on fish immunity in response to MPs is poorly defined. In particular, little is known regarding mucosal immunity and the role of mucins. In this study, marine medaka (Oryzias melastigma) larvae were exposed to 6.0 µm beads of polystyrene microplastics (PS-MPs) at three environmentally relevant concentrations (102 particles/L, 104 particles/L, and 106 particles/L) for 14 days. The experiment was carried out to explore the developmental and behavioural indices, the transcriptional profiles of mucins, pro-inflammatory, immune, metabolism and antioxidant responses related genes, as well as the accumulation of PS-MPs in larvae. The results revealed that PS-MPs were observed in the gastrointestinal tract, with a concentration- and exposure time-dependent manner. No significant difference in the larval mortality was found between the treatment groups and the control, whereas the body length of larvae demonstrated a significant reduction at 106 particles/L on 14 days post-hatching. The swimming behaviour of the larvae became hyperactive under exposure to 104 and 106 particles/L PS-MPs. In addition, PS-MP exposure significantly up-regulated the mucin gene transcriptional levels of muc7-like and muc13-like, however down-regulated the mucin gene expression levels of heg1, muc2, muc5AC-like and muc13. The immune- and inflammation and metabolism-relevant genes (jak, stat-3, il-6, il-1ß, tnf-а, ccl-11, nf-κb, and sod) were significantly induced by PS-MPs at 104 and 106 particles/L compared to the control. Taken together, this study suggests that PS-MPs induced inflammation response and might obstruct the immune functions and retarded the growth of the marine medaka larvae even at environmentally relevant concentrations.

Cyclometalated Ru(II) ß-carboline complexes induce cell cycle arrest and apoptosis in human HeLa cervical cancer cells via suppressing ERK and Akt signaling.

Two new cyclometalated Ru(II)-ß-carboline complexes, [Ru(dmb)2(Cl-Ph-ßC)](PF6) (dmb = 4,4'-dimethyl-2,2'-bipyridine; Cl-Ph-ßC = Cl-phenyl-9H-pyrido[3,4-b]indole; RußC-3) and [Ru(bpy)2(Cl-Ph-ßC)](PF6) (bpy = 2,2'-bipyridine; RußC-4) were synthesized and characterized. The Ru(II) complexes display high cytotoxicity against HeLa cells, the stabilized human cervical cancer cell, with IC50 values of 3.2 ± 0.4 µM (RußC-3) and 4.1 ± 0.6 µM (RußC-4), which were considerably lower than that of non-cyclometalated Ru(II)-ß-carboline complex [Ru(bpy)2(1-Py-ßC)] (PF6)2 (61.2 ± 3.9 µM) by 19- and 15-folds, respectively. The mechanism studies indicated that both Ru(II) complexes could significantly inhibit HeLa cell migration and invasion, and effectively induce G0/G1 cell cycle arrest. The new Ru(II) complexes could also trigger apoptosis through activating caspase-3 and poly (ADP-ribose) polymerase (PARP), increasing the Bax/Bcl-2 ratio, enhancing reactive oxygen species (ROS) generation, decreasing mitochondrial membrane potential (MMP), and inducing cytochrome c release from mitochondria. Further research revealed that RußC-3 could deactivate the ERK/Akt signaling pathway thus inhibiting HeLa cell invasion and migration, and inducing apoptosis. In addition, RußC-3-induced apoptosis in HeLa cells was closely associated with the increase of intracellular ROS levels, which may act as upstream factors to regulate ERK and Akt pathways. More importantly, RußC-3 exhibited low toxicity on both normal BEAS-2B cells in vitro and zebrafish embryos in vivo. Consequently, the developed Ru(II) complexes have great potential on developing novel low-toxic anticancer drugs.

Concentrated thermionic solar cells using graphene as the collector: theoretical efficiency limit and design rules.

We propose an updated design on concentrated thermionic emission solar cells, which demonstrates a high solar-to-electricity energy conversion efficiency larger than 10% under 600 suns, by harnessing the exceptional electrical, thermal, and radiative properties of the graphene as a collector electrode. By constructing an analytical model that explicitly takes into account the non-Richardson behavior of the thermionic emission current from graphene, space charge effect in vacuum gap, and the various irreversible energy losses within the subcomponents, we perform detailed characterizations on the conversion efficiency limit and parametric optimum design of the proposed system. Under 800 suns, a maximum efficiency of 12.8% has been revealed, where current density is 3.87 A cm-2, output voltage is 1.76 V, emitter temperature is 1707 K, and collector temperature is 352 K. Moreover, we systematically compare the peak efficiencies of various configurations combining diamond or graphene, and show that utilizing diamond films as an emitter and graphene as a collector offers the highest conversion efficiency, thus revealing the important role of graphene in achieving high-performance thermionic emission solar cells. This work thus opens up new avenues to advance the efficiency limit of thermionic solar energy conversion and the development of next-generation novel-nanomaterial-based solar energy harvesting technology.

Microplastics in three typical benthic species from the Arctic: Occurrence, characteristics, sources, and environmental implications.

Microplastics (MPs) in the Arctic have raised increasing concern, but knowledge on MP contamination in benthic organisms from Arctic shelf regions, e.g., the Chukchi Sea is still limited. Therefore, the present study investigated the occurrence, characteristics, sources, and environmental implications of MPs in the three most common benthic species, namely sea anemone (Actiniidae und.), deposit-feeding starfish (Ctenodiscus crispatus), and snow crab (Chionoecetes opilio), from the Chukchi Sea. The abundances of MPs in the three benthic species were significantly greater than those from the Bering Sea, but lower than those from other regions globally. The top three compositions of MPs in the three species were polyester, nylon, and polyethylene terephthalate. The detection limit for MP size in the present study was 0.03 mm and the mean size of MP in the three species was 0.89 ± 0.06 mm. The surfaces of MPs found in the starfish and crabs were covered with many attachments, cracks, and hollows, while the surfaces of MPs found in the sea anemones were smooth, which was likely a consequence of different feeding behaviors. There was a significantly positive correlation between the abundances of MPs and other anthropogenic substances. The mean MP abundances in the sea anemones ranged from 0.2 items/individual to 1.7 items/individual, which was significantly higher than that in the deposit-feeding starfish (0.1-1.4 items/individual) and snow crabs (0.0-0.6 items/individual). Sea anemones inhabiting lower latitudes ingested relatively higher levels of MPs than those inhabiting higher latitudes. The MP abundances in the sea anemones are significantly and positively correlated with the seasonal reduced ratio of sea ice coverage from August to September. Our findings indicate that sea anemones could function as a bioindicator of MP pollution, and that the MPs in the benthos from the Chukchi Sea might originate from the melting sea ice, fishery activities and ocean currents.

Designing high-performance nighttime thermoradiative systems for harvesting energy from outer space.

Energy harvesting using thermoradiative systems has been extensively explored in recent years as a novel strategy for further reducing our energy footprint. However, the nighttime application, thermodynamic limit, and optimal design of such a system remain largely unaddressed so far. Here we propose an improved nighttime thermoradiative system (NTS) for electrical power generation by optically coupling Earth's surface with outer space. Our theoretical model predicts that the NTS operating with Earth (deep space) at 300 K (3 K) yields a maximum power density of 12.3Wm-2 with an efficiency limit of 18.5%, which is potentially more advantageous than previous nighttime energy harvesting systems, such as a nighttime thermoelectric generator. We find that optimizing the thickness of the active layer, enhancing thermal infrared emission, and employing a silver backreflector for photon recycling are crucially important in improving system performance. This Letter provides new insights for the optimal designs of NTSs and paves the way toward practical nighttime power generation.

Biomonitoring of aromatic hydrocarbons in clam Meretrix meretrix from an emerging urbanization area, and implications for human health.

Pollution with total petroleum hydrocarbons (TPHs) is a global concern and particularly in coastal environments. Polycyclic aromatic hydrocarbons (PAHs) are regarded as the most toxic components of TPHs and they can also be derived from other sources. Fangcheng Port is considered as a representative emerging coastal city in China, but the status, sources, and hazards to organisms and humans with respect to contamination with PAHs and TPHs are unknown in the coastal regions of this area. Therefore, in this study, we cloned cytochrome P450 family genes (CYP1A1, CYP3A, and CYP4) and heat shock protein 70 gene (HSP70) in the clam Meretrix meretrix as well as optimizing the method for measuring the 7-ethoxyresorufin O-deethylase activity. These molecular indicators and four specific physiological indexes were found to be appropriate biomarkers for indicating the harmful effects of PAHs and TPHs on clams after exposure to the crude oil water-soluble fraction. In field monitoring surveys, we found that the 2- and 3-ring PAHs were dominant in the clams whereas the 4- to 6-ring PAHs were dominant in the sediments at each site. The PAH levels (3.63-12.77 ng/g wet weight) in wild clams were lower, whereas the TPH levels (13.25-70.50 µg/g wet weight) were higher compared with those determined previous in China and elsewhere. The concentrations of PAHs and TPHs in the sediments (19.20-4215.76 ng/g and 3.65-866.40 µg/g dry weight) were moderate compared with those in other global regions. Diagnostic ratio analysis demonstrated that the PAHs were derived mainly from pyrogenic sources. The TPHs may have come primarily from industrial effluents, land and maritime transportation, or fishing activities. The Integrated Biomarker Response version 2 indexes indicated that the clams collected from site S5 exhibited the most harmful effects due to contamination by PAHs and TPHs. Human health risk assessments demonstrated that the risks due to PAHs and TPHs following the consumption of clams can be considered acceptable. Our results suggest that continuous monitoring of contamination by PAHs and TPHs is recommended in this emerging coastal city as well as assessing their human health risks.

Cytotoxicity in vitro, cellular uptake, localization and apoptotic mechanism studies induced by ruthenium(II) complex.

Ruthenium-based complexes have been regarded as one of the most potential metal-based candidates for anticancer therapy. Herein, two ruthenium (II) methylimidazole complexes [Ru(MeIm)4(4npip)]2+ (complex 1) and [Ru(MeIm)4(4mopip)]2+ (complex 2) were synthesized and evaluated for their in vitro anticancer activities. The results showed that these ruthenium (II) methylimidazole complexes exhibited moderate antitumor activity comparable with cisplatin against A549, NCI-H460, MCF-7 and HepG2 human cancer cells, but with less toxicity to a human normal cell line HBE. Intracellular distribution studies suggested that complex 2 selectively localized in the mitochondria. Mechanism studies indicated that complex 2 caused cell cycle arrest at G0/G1 phase by regulating cell cycle relative proteins and induced apoptosis through intrinsic pathway, which involved mitochondrial dysfunction, reactive oxygen species (ROS) accumulation and ROS-mediated DNA damage. Further, studies by western blotting suggested that MAPK and AKT signaling pathways were involved in complex 2-induced apoptosis, and they were regulated by the level of ROS. Overall, these findings suggested that complex 2 could be a candidate for further evaluation as a chemotherapeutic agent in the treatment of cancers.

A novel purification procedure for recombinant human serum albumin expressed in Pichia pastoris.

Plasma-derived human serum albumin (pHSA) has important applications in many clinical indications, including blood loss, serious burn, or hemorrhagic shock. The limited supply and potential infectious pathogen contamination of pHSA have stimulated the development of recombinant human serum albumin (rHSA). However, rHSA often entraps endogenous or exogenous impurities, including color pigments and polysaccharides. Therefore, the purification of rHSA to high purity remains the bottleneck in large-scale production of rHSA. Herein we report a novel two-step purification protocol for rHSA generated from Pichia pastoris. In the first step, rHSA was partially unfolded to expose impurities entrapped into rHSA and was then removed. In the second step, rHSA was crystallized to further remove impurities. Through this procedure, the pigment content (A350/A280) and polysaccharides content of rHSA were reduced to 0.0141 and 0.253 µg/mg, respectively, which were comparable to pHSA. In addition, the secondary structure and bioactivity of purified rHSA are preserved. The purification procedure developed in this study is a simple, short and low cost method to produce active rHSA, or rHSA-fusion proteins, to high purity, and also suitable for the purification of other disulfide-rich proteins.

Negative illumination thermoradiative solar cell.

The negative illumination thermoradiative solar cell (NITSC) consisting of a concentrator, an absorber, and a thermoradiative cell (TRC) is established, where the radiation and reflection losses from the absorber to the environment and the radiation loss from the TRC to the environment are taken into consideration. The power output and overall efficiency of the NITSC are analytically derived. The operating temperature of the TRC is determined through the thermal equilibrium equations, and the efficiency of the NITSC is calculated through the optimization of the output voltage of the TRC and the concentrating factor for a given value of the bandgap. Moreover, the maximum efficiencies of the NITSC at different conditions and the optimal values of the bandgap are determined, and consequently, the corresponding optimum operating conditions are obtained. The results obtained here will be helpful for the optimum design and operation of TRCs.

Rapid killing of bacteria by a new type of photosensitizer.

Photodynamic antimicrobial chemotherapy (PACT) uses non-traditional mechanisms (free radicals) and is a highly advocated method with promise of inactivating drug-resistance bacteria for local infections. However, there is no related drug used in clinical practice yet. Therefore, new photosensitizers for PACT are under active development. Here, we report the synthesis of a series of photosensitizers with variable positive charges (ZnPc(TAP)4n+, n = 0, 4, 8, 12) and their inactivation against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The binding kinetics of ZnPc(TAP)4n+ to bacteria were measured by flow cytometer. Reactive oxygen species (ROS) generation mechanism of the photosensitizers was studied. The toxicity of these compounds to human blood cells was also evaluated. These compounds showed negligible toxicity against human erythocytes but potent bactericidal effects. The compound with 8 positive charges, ZnPc(TAP)48+, turned out to have the strongest antibacterial effect among this series of compounds, giving IC50 value of 59 nM at a light dosage of 5 J/cm2 toward E. coli. For a multi-resistant E. coli strain, ZnPc(TAP)48+ decreased the bacteria load by 1000-fold at a concentration of 1 µM. Interestingly, ZnPc(TAP)412+, instead of ZnPc(TAP)48+, exhibited the highest amount of binding to bacteria. Flow cytometry studies showed that all PSs have fast binding onto bacteria, reaching saturated binding within 5 min. Mechanistically, ZnPc(TAP)412+ generated ROS primarily via Type I mechanism, while ZnPc(TAP)44+ or ZnPc(TAP)48+ created ROS by both type I and type II mechanisms. ZnPc(TAP)4n+ are highly potent, rapid-acting and non-toxic photosensitizers capable of inactivating bacteria.

Docking and molecular dynamics studies of the binding between Peloruside A and tubulin.

The molecular docking, MD simulation and binding free energy calculation were performed to explore the probable binding modes between PLA and tubulin. Through docking study, three possible binding sites for PLA were speculated as follows: the taxane site, the alternative site and a new site in α-tubulin. Then, 12.0 ns MD simulations show that these binding modes predicted by docking have been changed more or less, whereas the MD simulations offer more reliable binding details. The MM-PBSA binding free-energy calculations reasonably identify that the taxane site is the most favorable binding site of PLA and the alternative site is the secondary one, which can be used to explain some experimental facts. These studies theoretically resolve the priority of binding sites for PLA and offer the reliable binding modes between PLA and tubulin, and thus help to understanding the action mechanism for this kind of inhibitor.

Cyclometalated ruthenium complexes overcome cisplatin resistance through PI3K/mTOR/Nrf2 signaling pathway.

Currently, cisplatin resistance remains a primary clinical obstacle in the successful treatment of non-small cell lung cancer. Here, we designed, synthesized, and characterized two novel cyclometalated Ru(II) complexes, [Ru(bpy)2(1-Ph-7-OCH3-IQ)] (PF6) (bpy = 2,2'-bipyridine, IQ = isoquinoline, RuIQ7)and [Ru(bpy)2(1-Ph-6,7-(OCH3)2-IQ)] (PF6) (RuIQ8). As experimental controls, we prepared complex [Ru(bpy)2(1-Ph-IQ)](PF6) (RuIQ6) lacking a methoxy group in the main ligand. Significantly, complexes RuIQ6-8 displayed higher in vitro cytotoxicity when compared to ligands, precursor cis-[Ru(bpy)2Cl2], and clinical cisplatin. Mechanistic investigations revealed that RuIQ6-8 could inhibit cell proliferation by downregulating the phosphorylation levels of Akt and mTOR proteins, consequently affecting the rapid growth of human lung adenocarcinoma cisplatin-resistant cells A549/DDP. Moreover, the results from qRT-PCR demonstrated that these complexes could directly suppress the transcription of the NF-E2-related factor 2 gene, leading to the inhibition of downstream multidrug resistance-associated protein 1 expression and effectively overcoming cisplatin resistance. Furthermore, the relationship between the chemical structures of these three complexes and their anticancer activity, ability to induce cell apoptosis, and their efficacy in overcoming cisplatin resistance has been thoroughly examined and discussed. Notably, the toxicity test conducted on zebrafish embryos indicated that the three Ru-IQ complexes displayed favorable safety profiles. Consequently, the potential of these developed compounds as innovative therapeutic agents for the efficient and low-toxic treatment of NSCLC appears highly promising.

Optimal figure of merit of low-dissipation quantum refrigerators.

The Drazin inverse of the Liouvillian superoperator provides a solution to determine the dynamics of a time-dependent system governed by the Markovian master equation. Under the condition of slow driving, the perturbation expansion of the density operator of the system in powers of time can be derived. As an application, a finite-time cycle model of the quantum refrigerator driven by a time-dependent external field is established. The method of the Lagrange multiplier is adopted as a strategy to find the optimal cooling performance. The figure of merit given by the product of the coefficient of performance and the cooling rate is taken as a new objective function, and, consequently, the optimally operating state of the refrigerator is revealed. The effects of the frequency exponent determining dissipation characteristics on the optimal performance of the refrigerator are discussed systemically. The results obtained show that the adjacent areas of the state of the maximum figure of merit are the best operation region of low-dissipative quantum refrigerators.

Gadoxetic acid-enhanced MRI combined with T1 mapping and clinical factors to predict Ki-67 expression of hepatocellular carcinoma.

Objectives: To explore the predictive value of gadoxetic acid-enhanced magnetic resonance imaging (MRI) combined with T1 mapping and clinical factors for Ki-67 expression in hepatocellular carcinoma (HCC). Methods: A retrospective study was conducted on 185 patients with pathologically confirmed solitary HCC from two institutions. All patients underwent preoperative T1 mapping on gadoxetic acid-enhanced MRI. Patients from institution I (n = 124) and institution II (n = 61) were respectively assigned to the training and validation sets. Univariable and multivariable analyses were performed to assess the correlation of clinico-radiological factors with Ki-67 labeling index (LI). Based on the significant factors, a predictive nomogram was developed and validated for Ki-67 LI. The performance of the nomogram was evaluated on the basis of its calibration, discrimination, and clinical utility. Results: Multivariable analysis showed that alpha-fetoprotein (AFP) levels > 20ng/mL, neutrophils to lymphocyte ratio > 2.25, non-smooth margin, tumor-to-liver signal intensity ratio in the hepatobiliary phase ≤ 0.6, and post-contrast T1 relaxation time > 705 msec were the independent predictors of Ki-67 LI. The nomogram based on these variables showed the best predictive performance with area under the receiver operator characteristic curve (AUROC) 0.899, area under the precision-recall curve (AUPRC) 0.946 and F1 score of 0.912; the respective values were 0.823, 0.879 and 0.857 in the validation set. The Kaplan-Meier curves illustrated that the cumulative recurrence probability at 2 years was significantly higher in patients with high Ki-67 LI than in those with low Ki-67 LI (39.6% [53/134] vs. 19.6% [10/51], p = 0.011). Conclusions: Gadoxetic acid-enhanced MRI combined with T1 mapping and several clinical factors can preoperatively predict Ki-67 LI with high accuracy, and thus enable risk stratification and personalized treatment of HCC patients.

The positive roles of influent species immigration in mitigating membrane fouling in membrane bioreactors treating municipal wastewater.

The influence of influent species immigration (ISI) on membrane fouling behaviors of membrane bioreactors (MBRs) treating municipal wastewater remains elusive, leading to an incomprehensive understanding of fouling ecology in MBRs. To address this issue, two anoxic/aerobic MBRs, which were fed with raw (named MBR-C) and sterilized (MBR-E) municipal wastewater, were operated. Compared with the MBR-E, the average fouling rate of the MBR-C was lowered by 30% over the long-term operation. In addition, the MBR-E sludge had significantly higher unified membrane fouling index and biofilm formation potential than the MBR-C sludge. Considerably larger flocs size and lower soluble microbial products (SMP) concentrations were observed in the MBR-C than in the MBR-E. Moreover, the 16S rRNA gene sequencing results showed that highly diverse and abundant populations responsible for floc-forming, hydrolysis/fermentation and SMP degradation readily inhabited the influent, shaping a unique microbial niche. Based on species mass balance-based assessment, most of these populations were nongrowing and their relative abundances were higher in the MBR-C than in the MBR-E. This suggested an important contribution of the ISI on the assemblage of these bacteria, thus supporting the increased flocs size and lowered SMP concentrations in the MBR-C. Moreover, the SMP-degrading related bacteria and functional pathways played a more crucial role in the MBR-C ecosystem as revealed by the bacterial co-occurrence network and Picrust2 analysis. Taken together, this study reveals the positive role of ISI in fouling mitigation and highlights the necessity for incorporating influent wastewater communities for fouling control in MBR plants.

Multiparametric MRI combined with clinical factors to predict glypican-3 expression of hepatocellular carcinoma.

Objectives: The present study aims at establishing a noninvasive and reliable model for the preoperative prediction of glypican 3 (GPC3)-positive hepatocellular carcinoma (HCC) based on multiparametric magnetic resonance imaging (MRI) and clinical indicators. Methods: As a retrospective study, the subjects included 158 patients from two institutions with surgically-confirmed single HCC who underwent preoperative MRI between 2020 and 2022. The patients, 102 from institution I and 56 from institution II, were assigned to the training and the validation sets, respectively. The association of the clinic-radiological variables with the GPC3 expression was investigated through performing univariable and multivariable logistic regression (LR) analyses. The synthetic minority over-sampling technique (SMOTE) was used to balance the minority group (GPC3-negative HCCs) in the training set, and diagnostic performance was assessed by the area under the curve (AUC) and accuracy. Next, a prediction nomogram was developed and validated for patients with GPC3-positive HCC. The performance of the nomogram was evaluated through examining its calibration and clinical utility. Results: Based on the results obtained from multivariable analyses, alpha-fetoprotein levels > 20 ng/mL, 75th percentile ADC value < 1.48 ×103 mm2/s and R2* value ≥ 38.6 sec-1 were found to be the significant independent predictors of GPC3-positive HCC. The SMOTE-LR model based on three features achieved the best predictive performance in the training (AUC, 0.909; accuracy, 83.7%) and validation sets (AUC, 0.829; accuracy, 82.1%) with a good calibration performance and clinical usefulness. Conclusions: The nomogram combining multiparametric MRI and clinical indicators is found to have satisfactory predictive efficacy for preoperative prediction of GPC3-positive HCC. Accordingly, the proposed method can promote individualized risk stratification and further treatment decisions of HCC patients.

Zebrafish: A Model Deciphering the Impact of Flavonoids on Neurodegenerative Disorders.

Over the past century, advances in biotechnology, biochemistry, and pharmacognosy have spotlighted flavonoids, polyphenolic secondary metabolites that have the ability to modulate many pathways involved in various biological mechanisms, including those involved in neuronal plasticity, learning, and memory. Moreover, flavonoids are known to impact the biological processes involved in developing neurodegenerative diseases, namely oxidative stress, neuroinflammation, and mitochondrial dysfunction. Thus, several flavonoids could be used as adjuvants to prevent and counteract neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Zebrafish is an interesting model organism that can offer new opportunities to study the beneficial effects of flavonoids on neurodegenerative diseases. Indeed, the high genome homology of 70% to humans, the brain organization largely similar to the human brain as well as the similar neuroanatomical and neurochemical processes, and the high neurogenic activity maintained in the adult brain makes zebrafish a valuable model for the study of human neurodegenerative diseases and deciphering the impact of flavonoids on those disorders.