Electrochemical sensor based on Cu2-xS/graphene heterostructures for sub-picomolar dopamine detection.

Detecting dopamine (DA) in biological samples is vital to understand its crucial role in numerous physiological processes, such as motion, cognition, and reward stimulus. In this work, p-type graphene on sapphire, synthesized via chemical vapor deposition, serves as substrate for the preparation of p-type Cu2-xS films through solid-phase sulfurization. The optimized Cu2-xS/graphene heterostructure, prepared at 250 °C using a 15-nm copper film sulfurized for 2 h, exhibits superior electron transfer performance, ideal for electrochemical sensing. It is confirmed that the spontaneous charge transfer from graphene to Cu2-xS, higher Cu(II)/Cu(I) ratio (~ 0.8), and the presence of well-defined nanocrystalline structures with an average size of ~ 35 nm in Cu2-xS significantly contribute to the improved electron transfer of the heterostructure. The electrochemical sensor based on Cu2-xS/graphene heterostructure demonstrates remarkable sensitivity towards DA, with a detection limit as low as 100 fM and a dynamic range greater than 109 from 100 fM to 100 µM. Additionally, it exhibits excellent selectivity even in the presence of uric acid and ascorbic acid 100 times higher, alongside notable storage and measurement stability and repeatability. Impressively, the sensor also proves capable of detecting DA concentrations as low as 100 pM in rat serum, showcasing its potential for clinically relevant analytes and promising applications in sensitive, selective, reliable, and efficient point-of-care diagnostics.

Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study.

Little is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004-2008) of the China Kadoorie Biobank to estimate the associations between autosomal mCAs and bladder cancer (ICD-10: C67). A total of 2874 autosomal mCAs events among 2612 carriers (2.6%) were detected. After a median follow-up of 12.4 years, we discovered that participants with all autosomal mCAs exhibited higher risks of bladder cancer, with a multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of 2.60 (1.44, 4.70). The estimate of such association was even stronger for mosaic loss events (HR [95% CI]: 6.68 [2.92, 15.30]), while it was not significant for CN-LOH events. Both expanded (cell fraction ≥10%) and non-expanded autosomal mCAs, as well as mosaic loss, were associated with increased risks of bladder cancer. Of interest, physical activity (PA) significantly modified the associations of autosomal mCAs and mosaic loss (Pinteraction = 0.038 and 0.012, respectively) with bladder cancer. The increased risks of bladder cancer were only observed with mCAs and mosaic loss among participants with a lower level of PA (HR [95% CI]: 5.11 [2.36, 11.09] and 16.30 [6.06, 43.81]), but not among participants with a higher level of PA. Our findings suggest that peripheral leukocyte autosomal mCAs may represent a novel risk factor for bladder cancer, and PA may serve as a potential intervention target for mCAs carriers.

BAP1-mediated MAFF deubiquitylation regulates tumor growth and is associated with adverse outcomes in colorectal cancer.

BACKGROUND: Despite improvements in colorectal cancer (CRC) treatment, the prognosis for advanced CRC patients remains poor. Disruption of protein stability is one of the important factors in cancer development and progression. In this study, we aim to identify and analyze novel dysregulated proteins in CRC, assessing their significance and the mechanisms. METHODS: Using quantitative proteomics, expression pattern analysis, and gain-of-function/loss-of-function experiments, we identify novel functional protein dysregulated by ubiquitin-proteasome axis in CRC. Prognostic significance was evaluated in a training cohort of 546 patients and externally validated in 794 patients. Mechanistic insights are gained through molecular biology experiments, deubiquitinating enzymes (DUBs) expression library screening, and RNA sequencing. RESULTS: MAFF protein emerged as the top novel candidate substrate regulated by ubiquitin-proteasome in CRC. MAFF protein was preferentially downregulated in CRC compared to adjacent normal tissues. More importantly, multicenter cohort study identified reduced MAFF protein expression as an independent predictor of overall and disease-free survival in CRC patients. The in vitro and vivo assays showed that MAFF overexpression inhibited CRC growth, while its knockdown had the opposite effect. Intriguingly, we found the abnormal expression of MAFF protein was predominantly regulated via ubiquitination of MAFF, with K48-ubiquitin being dominant. BAP1 as a nuclear deubiquitinating enzyme (DUB), bound to and deubiquitinated MAFF, thereby stabilizing it. Such stabilization upregulated DUSP5 expression, resulting in the inhibition of ERK phosphorylation. CONCLUSIONS: This study describes a novel BAP1-MAFF signaling axis which is crucial for CRC growth, potentially serving as a therapeutic target and a promising prognostic biomarker for CRC.

Role of lifestyle factors on the development and long-term prognosis of pneumonia and cardiovascular disease in the Chinese population.

BACKGROUND: Whether adherence to a healthy lifestyle is associated with a lower risk of developing pneumonia and a better long-term prognosis remains unclear. This study aimed to investigate associations of individual and combined lifestyle factors (LFs) with the incidence risk and long-term prognosis of pneumonia hospitalization. METHODS: Using data from the China Kadoorie Biobank study, we used the multistate models to investigate the role of five high-risk LFs, including smoking, excessive alcohol drinking, unhealthy dietary habits, physical inactivity, and unhealthy body shape, alone or in combination in the transitions from a generally healthy state at baseline to pneumonia hospitalization or cardiovascular disease (CVD, regarded as a reference outcome), and subsequently to mortality. RESULTS: Most of the five high-risk LFs were associated with increased risks of transitions from baseline to pneumonia and from pneumonia to death, but with different risk estimates. The greater the number of high-risk LFs, the higher the risk of developing pneumonia and long-term mortality risk after pneumonia, with the strength of associations comparable to that of LFs and CVD. Compared to participants with 0-1 high-risk LF, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for transitions from baseline to pneumonia and from pneumonia to death in those with five high-risk LFs were 1.43 (1.28-1.60) and 1.98 (1.61-2.42), respectively. Correspondingly, the respective HRs (95% CIs) for transitions from baseline to CVD and from CVD to death were 2.00 (1.89-2.11) and 1.44 (1.30-1.59), respectively. The risk estimates changed slightly when further adjusting for the presence of major chronic diseases. CONCLUSION: In this Chinese population, unhealthy LFs were associated with an increased incidence and long-term mortality risk of pneumonia.

The AKT inhibitor AZD5363 elicits synthetic lethality in ARID1A-deficient gastric cancer cells via induction of pyroptosis.

BACKGROUND: Gastric cancer (GC) is a deadly disease with poor overall survival and limited therapeutic options. Genetic alterations such as mutations and/or deletions in chromatin remodeling gene AT-rich interactive domain 1 A (ARID1A) occur frequently in GC. Although ARID1A mutations/deletions are not a druggable target for conventional treatments, novel therapeutic strategies based on a synthetic lethal approach may be effective for the treatment of ARID1A-deficient cancers. METHODS: A kinase inhibitor library containing 551 compounds was screened in ARID1A isogenic GC cells for the ability to induce synthetic lethality effect. Selected hits' activity was validated, and the mechanism of the most potent candidate drug, AKT inhibitor AD5363 (capivasertib), on induction of the synthetic lethality with ARID1A deficiency was investigated. RESULTS: After robust vulnerability screening of 551 diverse protein kinase inhibitors, we identified the AKT inhibitor AZD5363 as being the most potent lead compound in inhibiting viability of ARID1A-/- cells. A synthetic lethality between loss of ARID1A expression and AKT inhibition by AZD5363 was validated in both GC cell model system and xenograft model. Mechanistically, AZD5363 treatment induced pyroptotic cell death in ARID1A-deficient GC cells through activation of the Caspase-3/GSDME pathway. Furthermore, ARID1A occupied the AKT gene promoter and regulated its transcription negatively, thus the GC cells deficient in ARID1A showed increased expression and phosphorylation of AKT. CONCLUSIONS: Our study demonstrates a novel synthetic lethality interaction and unique mechanism between ARID1A loss and AKT inhibition, which may provide a therapeutic and mechanistic rationale for targeted therapy on patients with ARID1A-defective GC who are most likely to be beneficial to AZD5363 treatment.

Biothiols-activated near-infrared frequency up-conversion luminescence probe for early evaluation of drug-induced hepatotoxicity.

A novel biothiols-sensitive near-infrared (NIR) fluorescent probe RhDN based on a rhodamine skeleton was developed for early detection of drug-induced hepatotoxicity in living mice. RhDN can be used not only as a conventional large stokes shift fluorescent (FL) probe, but also as a kind of anti-Stokes frequency upconversion luminescence (FUCL) molecular probe, which represents a long wavelength excitation (808 nm) to short wavelength emission (760 nm), and response to Cys/Hcy/GSH with high sensitivity. Compared with traditional FL methods, the FUCL method exhibited a lower detection limit of Cys, Hcy, and GSH in 75.1 nM, 101.8 nM, and 84.9 nM, respectively. We exemplify RhDN for tracking endogenously biothiols distribution in living cells and further realize real-time in vivo bioimaging of biothiols activity in mice with dual-mode luminescence system. Moreover, RhDN has been successfully applied to visualize the detection of drug-induced hepatotoxicity in living mice. Overall, this report presents a unique approach to the development of large stokes shift NIR FUCL molecular probes for in vitro and in vivo biothiols biosensing.

Male Germ Cell Specification in Plants.

Germ cells (GCs) serve as indispensable carriers in both animals and plants, ensuring genetic continuity across generations. While it is generally acknowledged that the timing of germline segregation differs significantly between animals and plants, ongoing debates persist as new evidence continues to emerge. In this review, we delve into studies focusing on male germ cell specifications in plants, and we summarize the core gene regulatory circuits in germ cell specification, which show remarkable parallels to those governing meristem homeostasis. The similarity in germline establishment between animals and plants is also discussed.

Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1.

Generally shortened 3' UTR due to alternative polyadenylation (APA) is widely observed in cancer, but its regulation mechanisms for cancer are not well characterized. Here, with profiling of APA in colorectal cancer tissues and poly(A) signal editing, we firstly identified that the shortened 3' UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and migration. We found that liquid-liquid phase separation (LLPS) of PABPN1 is reduced albeit with higher expression in cancer, and the reduction of LLPS leads to the shortened 3' UTR of CTNNBIP1 and promotes cell proliferation and migration. Notably, the splicing factor SNRPD2 upregulated in colorectal cancer, can interact with glutamic-proline (EP) domain of PABPN1, and then disrupt LLPS of PABPN1, which attenuates the repression effect of PABPN1 on the proximal poly(A) sites. Our results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1, suggesting that regulation of APA by interfering LLPS of 3' end processing factor may have the potential as a new way for the treatment of cancer.

Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer.

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.

OTUD1 enhances gastric cancer aggressiveness by deubiquitinating EBV-encoded protein BALF1 to stabilize the apoptosis inhibitor Bcl-2.

The Epstein-Barr virus (EBV) is implicated in several cancers, including EBV-associated gastric cancer (EBVaGC). This study focuses on EBV-encoded BALF1 (BamH1 A fragment leftward reading frame 1), a key apoptosis regulator in EBV-related cancers, whose specific impact on EBVaGC was previously unknown. Our findings indicate that BALF1 overexpression in gastric cancer cells significantly enhances their proliferation, migration, and resistance to chemotherapy-induced apoptosis, confirming BALF1's oncogenic potential. A novel discovery is that BALF1 undergoes degradation via the ubiquitin-proteasome pathway. Through analysis of 69 deubiquitinating enzymes (DUBs), ovarian tumor protease (OTU) domain-containing protein 1 (OTUD1) emerged as a vital regulator for maintaining BALF1 protein stability. Furthermore, BALF1 was found to play a role in regulating the stability of the B-cell lymphoma-2 (Bcl-2) protein, increasing its levels through deubiquitination. This mechanism reveals BALF1's multifaceted oncogenic role in gastric cancer, as it contributes both directly and indirectly to cancer progression, particularly by stabilizing Bcl-2, known for its anti-apoptotic characteristics. These insights significantly deepen our understanding of EBV's involvement in the pathogenesis of gastric cancer. The elucidation of OTUD1's role in BALF1 regulation and its influence on Bcl-2 stabilization provide new avenues for therapeutic intervention in EBVaGC, bridging the gap between viral oncogenesis and cellular protein regulation and offering a more holistic view of gastric cancer development under the influence of EBV.

A Single-Shot Scattering Medium Imaging Method via Bispectrum Truncation.

Imaging using scattering media is a very important yet challenging technology. As one of the most widely used scattering imaging methods, speckle autocorrelation technology has important applications in several fields. However, traditional speckle autocorrelation imaging methods usually use iterative phase recovery algorithms to obtain the Fourier phase of hidden objects, posing issues such as large data calculation volumes and uncertain reconstruction results. Here, we propose a single-shot scattering imaging method based on the bispectrum truncation method. The bispectrum analysis is utilized for hidden object phase recovery, the truncation method is used to avoid the computation of redundant data when calculating the bispectrum data, and the method is experimentally verified. The experimental results show that our method does not require uncertain iterative calculations and can reduce the bispectrum data computation by more than 80% by adjusting the truncation factor without damaging the imaging quality, which greatly improves imaging efficiency. This method paves the way for rapid imaging through scattering media and brings benefits for imaging in dynamic situations.

The effects of video double-lumen tubes on intubation complications in patients undergoing thoracic surgery: A randomised controlled study.

BACKGROUND: Tracheal injuries, vocal cord injuries, sore throat and hoarseness are common complications of double-lumen tube (DLT) intubation. OBJECTIVE: This study aimed to evaluate the effects of 'video double-lumen tubes' (VDLTs) on intubation complications in patients undergoing thoracic surgery. DESIGN: A randomised controlled study. SETTINGT: Xuzhou Cancer Hospital, Xuzhou, China, from January 2023 to June 2023. PATIENTS: One hundred eighty-two patients undergoing elective thoracic surgery with one-lung ventilation were randomised into two groups: 90 in the DLT group and 92 in the VDLT group. INTERVENTION: VDLT was selected for intubation in the VDLT group, and DLT was selected for intubation in the DLT group. A fibreoptic bronchoscope (FOB) was used to record tracheal and vocal cord injuries. MAIN OUTCOME MEASURES: The primary outcomes were the incidence of moderate-to-severe tracheal injury and the incidence of vocal cord injury. The secondary outcomes included the incidence and severity of postoperative 24 and 48 h sore throat and hoarseness. RESULTS: The incidence of moderate-to-severe tracheal injury was 32/90 (35.6%) in the DLT group, and 45/92 (48.9%) in the VDLT group ( P  = 0.077; relative risk 1.38, 95% CI, 0.97 to 1.95). The incidence of vocal cord injury was 31/90 (34.4%) and 34/92 (37%) in the DLT and VDLT groups, respectively ( P  = 0.449). The incidence of postoperative 24 h sore throat and hoarseness was significantly higher in the VDLT group than in the DLT group (for sore throat: P  = 0.032, relative risk 1.63, 95% CI, 1.03 to 2.57; for hoarseness: P  = 0.018, relative risk 1.48, 95% CI, 1.06 to 2.06). CONCLUSION: There was no statistically significant difference in the incidence of moderate-to-severe tracheal injury and vocal cord injury between DLTs and VDLTs. While improving the first-attempt success rate, intubation with VDLT increased the incidence of postoperative 24 h sore throat and hoarseness. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR2300067348.

Using Diffraction Deep Neural Networks for Indirect Phase Recovery Based on Zernike Polynomials.

The phase recovery module is dedicated to acquiring phase distribution information within imaging systems, enabling the monitoring and adjustment of a system's performance. Traditional phase inversion techniques exhibit limitations, such as the speed of the sensor and complexity of the system. Therefore, we propose an indirect phase retrieval approach based on a diffraction neural network. By utilizing non-source diffraction through multiple layers of diffraction units, this approach reconstructs coefficients based on Zernike polynomials from incident beams with distorted phases, thereby indirectly synthesizing interference phases. Through network training and simulation testing, we validate the effectiveness of this approach, showcasing the trained network's capacity for single-order phase recognition and multi-order composite phase inversion. We conduct an analysis of the network's generalization and evaluate the impact of the network depth on the restoration accuracy. The test results reveal an average root mean square error of 0.086λ for phase inversion. This research provides new insights and methodologies for the development of the phase recovery component in adaptive optics systems.

PSEUDO-ETIOLATION IN LIGHT proteins reduce greening by binding GLK transcription factors.

Knocking out genes encoding proteins that downregulate the accumulation of pigments may lead to increases in crop quality and yield. PSEUDO-ETIOLATION IN LIGHT 1 (PEL1) downregulates the accumulation of carotenoids in carrot and chlorophyll in Arabidopsis and rice and may inhibit GOLDEN 2-LIKE (GLK) transcription factors. PEL1 belongs to a previously unstudied gene family found only in plants. We used CRISPR/Cas9 technology to knock out each member of the 4-member PEL gene family and both GLK genes in Arabidopsis. In pel mutants, chlorophyll levels were elevated in seedlings; after flowering, chloroplasts increased in size, and anthocyanin levels increased. Although the chlorophyll-deficient phenotype of glk1 glk2 was epistatic to pel1 pel2 pel3 pel4 in most of our experiments, glk1 glk2 was not epistatic to pel1 pel2 pel3 pel4 for the accumulation of anthocyanins in most of our experiments. The pel alleles attenuated growth, altered the accumulation of nutrients in seeds, disrupted an abscisic acid-inducible inhibition of seedling growth response that promotes drought tolerance, and affected the expression of genes associated with diverse biological functions, such as stress responses, cell wall metabolism hormone responses, signaling, growth, and the accumulation of phenylpropanoids and pigments. We found that PEL proteins specifically bind 6 transcription factors that influence the accumulation of anthocyanins, GLK2, and the carboxy termini of GLK1 and Arabidopsis thaliana myeloblastosis oncogene homolog 4 (AtMYB4). Our data indicate that the PEL proteins influence the accumulation of chlorophyll and many other processes, possibly by inhibiting GLK transcription factors and via other mechanisms, and that multiple mechanisms downregulate chlorophyll content.

Developing Computerized Adaptive Testing for a National Health Professionals Exam: An Attempt from Psychometric Simulations.

Introduction: The accurate assessment of health professionals' competence is critical for ensuring public health safety and quality of care. Computerized Adaptive Testing (CAT) based on the Item Response Theory (IRT) has the potential to improve measurement accuracy and reduce respondent burden. In this study, we conducted psychometric simulations to develop a CAT for evaluating the candidates' competence of health professionals. Methods: The initial CAT item bank was sourced from the Standardized Competence Test for Clinical Medicine Undergraduates (SCTCMU), a nationwide summative test in China, consisting of 300 multiple-choice items. We randomly selected response data from 2000 Chinese clinical medicine undergraduates for analysis. Two types of analyses were performed: first, evaluating the psychometric properties of all items to meet the requirements of CAT; and second, conducting multiple CAT simulations using both simulated and real response data. Results: The final CAT item bank consisted of 121 items, for which item parameters were calculated using a two-parameter logistic model (2PLM). The CAT simulations, based on both simulated and real data, revealed sufficient marginal reliability (coefficient of marginal reliability above 0.750) and criterion-related validity (Pearson's correlations between CAT scores and aggregate scores of the SCTCMU exceeding 0.850). Discussion: In national-level medical education assessment, there is an increasing need for concise yet valid evaluations of candidates' competence of health professionals. The CAT developed in this study demonstrated satisfactory reliability and validity, offering a more efficient assessment of candidates' competence of health professionals. The psychometric properties of the CAT could lead to shorter test durations, reduced information loss, and a decreased testing burden for participants.

Determination of seroprevalence and kinetics of humoral response using mpox virus A29 protein.

BACKGROUND: Mpox virus (MPXV), previously known as monkeypox virus, has spread globally in 2022. An accurate and convenient antibody test is essential for the determination of seroprevalence and for studying immune response after natural infection or vaccination. Most seroprevalence or vaccine studies used either live MPXV (or vaccinia virus [VACV]) or inactivated MPXV (or VACV) culture lysate for serological assays, but MPXV culture can only be performed in biosafety level 3 (BSL-3) facilities. Here, we developed and evaluated an enzyme immunoassay (EIA) based on the MPXV A29 surface envelope protein. METHODS: We compared the specificity of the MPXV A29, VACV A27, and VACV lysate EIA using serum specimens collected prior to the global spread of MPXV. Next, we performed these EIAs for serum specimens collected from two mpox patients and an MVA-BN vaccine recipient. We also assessed the kinetics of plasmblast and MPXV A29-specific B-cell response. RESULTS: Using sera collected from different age groups in Hong Kong, we found that most individuals, including those born before 1981 who have received the smallpox vaccine, tested negative using the MPXV A29 protein. MPXV A29-specific antibody could be detected in the serum of mpox patients and an MVA-BN recipient. In a mpox patient, the frequency of plasmablast and MPXV A29-specific B cell peaked on day 8 post-symptom onset and gradually decreased. Finally, we demonstrated that antibodies against the A29 protein can be used for immunofluorescence staining of MPXV-infected cells. CONCLUSIONS: MPXV A29 protein is suitable for studying the immune response against MPXV infection.

Since early 2022, mpox (monkeypox) has been reported in many countries where the disease is not regularly found to occur. The aim of the study was to develop and evaluate the performance of laboratory assays based on the mpox virus surface protein, named A29. We found our assays could accurately distinguish naturally infected cases from smallpox vaccine recipients as well as those who were neither infected nor vaccinated. Our assays provide a useful tool for studying the host immune response to mpox virus.

A comparison of micro-flocculation and ozonation as pretreatments for ultrafiltration: organic removal and membrane fouling.

Micro-flocculation and ozone were applied as pretreatments of ultrafiltration to treat sodium alginate (SA) and humic acid (HA) simulated water, respectively, to investigate the effects of different pretreatments of ultrafiltration (UF) on filtration flux and removal of organic matters. Regarding the SA simulated water, micro-flocculation helped to improve the dissolved organic carbon (DOC) removal efficiency highly, maximum DOC removal efficiency reached to 79.77%, due to the rejection of gel layer introduced by the alginate-aluminum complexes, but the gel layer had a negative impact on membrane flux. Compared with micro-flocculation, ozone as pretreatments had better ability to enhance the membrane specific flux, the maximum final specific flux remained as 0.786, larger than that of MF-UF process (0.574). Ozonation oxidizing SA into small organic molecules significantly reduced membrane fouling and filtration resistance, but also produced some dissolved organic matters hindering DOC removal of effluent. As for HA simulated water, both the micro-flocculation and ozone could effectively improve the specific flux, the final specific flux of MF-UF and ozone-UF were about 0.930, but MF-UF exhibited better DOC removal than ozone-UF, which avoided the introduction of additional dissolved organic matters.

Current status of porous coordination networks (PCNs) derived porphyrin spacers for cancer therapy.

INTRODUCTION: Porous coordination networks (PCNs) have been widely used in large number of applications such as light harvesting, catalysis, and biomedical applications. Inserting porphyrins into PCNs scaffolds can alleviate the solubility and chemical stability problems associated with porphyrin ligands and add functionality to PCNs. The discovery that some PCNs materials have photosensitizer and acoustic sensitizer properties has attracted significant attention in the field of biomedicine, particularly in cancer therapy. This article describes the latest applications of the porphyrin ligand-based family of PCNs in cancer chemodynamic therapy (CDT), photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), and combination therapies and offers some observations and reflections on them. AREAS COVERED: This article discusses the use of the PCN family of MOFs in cancer treatment, specifically focusing on chemodynamic therapy, sonodynamic therapy, photodynamic therapy, photothermal therapy, and combination therapy. EXPERT OPINION: Although a large number of PCNs have been developed for use in novel cancer therapeutic approaches, further improvements are needed to advance the use of PCNs in the clinic. For example, the main mechanism of action of PCNs against cancer and the metabolic processes in organisms, and how to construct PCNs that maintain good stability in the complex environment of organisms.

The NEAT Equating Via Chaining Random Forests in the Context of Small Sample Sizes: A Machine-Learning Method.

The part of responses that is absent in the nonequivalent groups with anchor test (NEAT) design can be managed to a planned missing scenario. In the context of small sample sizes, we present a machine learning (ML)-based imputation technique called chaining random forests (CRF) to perform equating tasks within the NEAT design. Specifically, seven CRF-based imputation equating methods are proposed based on different data augmentation methods. The equating performance of the proposed methods is examined through a simulation study. Five factors are considered: (a) test length (20, 30, 40, 50), (b) sample size per test form (50 versus 100), (c) ratio of common/anchor items (0.2 versus 0.3), and (d) equivalent versus nonequivalent groups taking the two forms (no mean difference versus a mean difference of 0.5), and (e) three different types of anchors (random, easy, and hard), resulting in 96 conditions. In addition, five traditional equating methods, (1) Tucker method; (2) Levine observed score method; (3) equipercentile equating method; (4) circle-arc method; and (5) concurrent calibration based on Rasch model, were also considered, plus seven CRF-based imputation equating methods for a total of 12 methods in this study. The findings suggest that benefiting from the advantages of ML techniques, CRF-based methods that incorporate the equating result of the Tucker method, such as IMP_total_Tucker, IMP_pair_Tucker, and IMP_Tucker_cirlce methods, can yield more robust and trustable estimates for the "missingness" in an equating task and therefore result in more accurate equated scores than other counterparts in short-length tests with small samples.

Integrated transcriptomics and metabolomics reveal protective effects on heart of hibernating Daurian ground squirrels.

Hibernating mammals are natural models of resistance to ischemia, hypoxia-reperfusion injury, and hypothermia. Daurian ground squirrels (spermophilus dauricus) can adapt to endure multiple torpor-arousal cycles without sustaining cardiac damage. However, the molecular regulatory mechanisms that underlie this adaptive response are not yet fully understood. This study investigates morphological, functional, genetic, and metabolic changes that occur in the heart of ground squirrels in three groups: summer active (SA), late torpor (LT), and interbout arousal (IBA). Morphological and functional changes in the heart were measured using hematoxylin-eosin (HE) staining, Masson staining, echocardiography, and enzyme-linked immunosorbent assay (ELISA). Results showed significant changes in cardiac function in the LT group as compared with SA or IBA groups, but no irreversible damage occurred. To understand the molecular mechanisms underlying these phenotypic changes, transcriptomic and metabolomic analyses were conducted to assess differential changes in gene expression and metabolite levels in the three groups of ground squirrels, with a focus on GO and KEGG pathway analysis. Transcriptomic analysis showed that differentially expressed genes were involved in the remodeling of cytoskeletal proteins, reduction in protein synthesis, and downregulation of the ubiquitin-proteasome pathway during hibernation (including LT and IBA groups), as compared with the SA group. Metabolomic analysis revealed increased free amino acids, activation of the glutathione antioxidant system, altered cardiac fatty acid metabolic preferences, and enhanced pentose phosphate pathway activity during hibernation as compared with the SA group. Combining the transcriptomic and metabolomic data, active mitochondrial oxidative phosphorylation and creatine-phosphocreatine energy shuttle systems were observed, as well as inhibition of ferroptosis signaling pathways during hibernation as compared with the SA group. In conclusion, these results provide new insights into cardio-protection in hibernators from the perspective of gene and metabolite changes and deepen our understanding of adaptive cardio-protection mechanisms in mammalian hibernators.