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The power grid CO2 emission factor is a critical parameter for accurately calculating indirect emissions from the electricity consumption side, serving as a core indicator for precisely quantifying the CO2 emission pathways at the consumption side. This study explores the temporal and spatial characteristics of the province-level power-grid CO2 emission factors from 2020 to 2035 and compares them with official-source factors. Moreover, it integrates historical direct-emission data to accurately quantify the importance of indirect emissions from the electricity consumption side. Additionally, it predicts the province-level indirect emissions and emission pathways under different scenarios from 2020 to 2035, quantifying the impacts of power grid CO2 emission factors with distinct temporal and spatial accuracies on provincial emission pathways. The results indicate that: (1) from 2020 to 2035, the power grid CO2 emission factors of all provinces are expected to exhibit sustained decreasing trends, and there are disparities between the existing publicly available power-grid CO2 emission factors and provincial levels in the study. (2) From 2010 to 2020, the indirect emissions from electricity consumption and their proportions in net electricity-importing provinces had gradually increased, with Beijing, Shanghai, and Zhejiang province having the largest proportions. (3) Under Scenarios 1 (constant power-grid CO2 emission factors on the national level) and 3 (constant power-grid CO2 emission factors on the provincial level), the indirect emissions from electricity consumption and total emissions of all provinces will be significantly higher than the estimated results in Scenarios 2 (dynamic power-grid CO2 emission factor on the national level) and 4 (dynamic power-grid CO2 emission factor on the provincial level). The estimation results of Scenarios 1 and 2 are projected to differ significantly from those of Scenarios 3 and 4. For provinces with large proportions of indirect emissions from electricity consumption, such as Beijing, Shanghai, and Guangdong, selecting power grid CO2 emission factors with different spatial accuracies is expected to have noticeable impacts on their total emissions, further leading to shifts in their peaking years. The research results can provide a reference for supporting the planning of carbon peaking pathways in various provinces and reducing the uncertainty in indirect emission forecasts.

Abstract Bispecific antibodies (bsAbs) hold promises for enhanced therapeutic potential surpassing that of their parental monoclonal antibodies. However, bsAbs pose great challenges in their manufacturing, and one of the common reasons is their susceptibility to aggregation. Building on previous studies demonstrating the functionality and potential manufacturability of Fab-scFv format bsAb, this investigation delved into the impact of environmental factors—such as pH, buffer types, ionic strength, protein concentrations, and temperatures—on its stability and the reversal of its self-associated aggregates. Mildly acidic, low-salt conditions were found optimal, ensuring bsAb stability for 30 days even at elevated temperature of 40 °C. Furthermore, these conditions facilitated the reversal of its self-associated aggregates to monomers during the initial 7-day incubation period. Our findings underscore the robustness and resilience of Fab-scFv format bsAb, further confirming its potential manufacturability despite its current absence as commercial products. Graphical Abstract

Abstract Glycogen storage, conversion and utilization in astrocytes play an important role in brain energy metabolism. The conversion of glycogen to lactate through glycolysis occurs through the coordinated activities of various enzymes and inhibition of this process can impair different brain processes including formation of long-lasting memories. To replenish depleted glycogen stores, astrocytes undergo glycogen synthesis, a cellular process that has been shown to require transcription and translation during specific stimulation paradigms. However, the detail nuclear signaling mechanisms and transcriptional regulation during glycogen synthesis in astrocytes remains to be explored. In this report, we study the molecular mechanisms of vasoactive intestinal peptide (VIP)-induced glycogen synthesis in astrocytes. VIP is a potent neuropeptide that triggers glycogenolysis followed by glycogen synthesis in astrocytes. We show evidence that VIP-induced glycogen synthesis requires CREB-mediated transcription that is calcium dependent and requires conventional Protein Kinase C but not Protein Kinase A. In parallel to CREB activation, we demonstrate that VIP also triggers nuclear accumulation of the CREB coactivator CRTC2 in astrocytic nuclei. Transcriptome profiles of VIP-induced astrocytes identified robust CREB transcription, including a subset of genes linked to glucose and glycogen metabolism. Finally, we demonstrate that VIP-induced glycogen synthesis shares similar as well as distinct molecular signatures with glucose-induced glycogen synthesis, including the requirement of CREB-mediated transcription. Overall, our data demonstrates the importance of CREB-mediated transcription in astrocytes during stimulus-driven glycogenesis.

Abstract Redox‐active materials that exhibit both electrochromism and electrofluorochromism have great potential as multifunctional elements in optoelectronics. Here, in situ spectroelectrochemistry is presented on NU‐1000, a zirconium pyrenetetrabenzoate metal–organic framework. A thin film of NU‐1000 exhibits reversible color changes between light yellow and dark blue when subjected to an alternating electrochemical potential. In situ fluorescence excitation‐emission spectral mapping elucidates a dominant blue emission of highly fluorescent electrochromic NU‐1000 that is being quenched via an oxidation reaction. Density‐functional theory calculations reveal the forbidden optical transition between the singly occupied molecular orbital (SOMO) and the lowest unoccupied molecular orbital (LUMO) in the oxidized linker as the cause of the quenching. Double potential step chronoamperometry measures response times as fast as a dozen seconds and excellent switching stability over 500 cycles without noticeable attenuation of the color contrast. These findings provide valuable insight into the electrochromism and electrofluorochromism in metal–organic frameworks, offering exciting opportunities for developing advanced multifunctional porous materials with potential applications in optoelectronics and sensing.

Microneedles (MNs) is an emerging technology that employs needles ranging from 10 to 1000 μm in height, as a minimally invasive technique for various procedures such as therapeutics, disease monitoring and diagnostics. The commonly used method of fabrication, micromolding, has the advantage of scalability, however, micromolding is unable to achieve rapid customizability in dimensions, geometries and architectures, which are the pivotal factors determining the functionality and efficacy of the MNs. 3D printing offers a promising alternative by enabling MN fabrication with high dimensional accuracy required for precise applications, leading to improved performance. Furthermore, enabled by its customizability and one-step process, there is propitious potential for growth for 3D-printed MNs especially in the field of personalized and on-demand medical devices. This review provides an overview of considerations for the key parameters in designing MNs, an introduction on the various 3D-printing techniques for fabricating this new generation of MNs, as well as highlighting the advancements in biomedical applications facilitated by 3D-printed MNs. Lastly, we offer some insights into the future prospects of 3D-printed MNs, specifically its progress towards translation and entry into market.

Abstract Bispecific antibody (bsAb), a novel therapeutic modality, provides excellent treatment efficacy, yet poses numerous challenges to downstream process development, which are mainly due to the intricate diversity of bsAb structures and impurity profiles. Ceramic hydroxyapatite (CHT), a mixed-mode medium, allows proteins to interact with its calcium sites (C-sites) through metal affinity and/or its phosphate sites (P-sites) through cation exchange interactions. This dual-binding capability potentially offers unique bind and elute behaviours for different proteins of interest, resulting in optimal product purity when suitable elution conditions are employed. In this study, the effectiveness of CHT as a polishing step for bsAb purification was investigated across three model molecules and benchmarked against the traditional cation exchange chromatography (CEX). For both asymmetric and symmetric IgG-like bsAb post Protein A eluates, at least 97% product purity was achieved after CHT polishing. CHT delivered a superior aggregate clearance to CEX, resulting in low high molecular weight (HMW) impurities (0.5%) and low process-related impurities in the product pools. Moreover, CHT significantly mitigated "chromatography-induced aggregation" whereas eightfold more HMW was generated by CEX. This study illustrated the developability of CHT in effectively eliminating low molecular weight (LMW) impurities through post-load-wash (PLW) optimization, resulting in an additional reduction of up to 48% in LMW impurities. A mechanistic explanation regarding the performance of impurity removal and mitigation of the chromatography-induced aggregation by CHT was proposed, illustrating unique CHT capability is potentially driven by C-site cooperation, of which effectiveness could depend on the bsAb composition and size. Graphical abstract

Advancing the performance and stability of lithium metal batteries is crucial for future energy storage devices. One of the major challenges for practical applications of Li metal batteries is to mitigate the formation of Li dendrites during cycling. In this work, we prepared a series of asymmetrically structured polyethersulfone (PES) membranes, consisting of a nanoporous skin layer and a bulk with macrovoids, by incorporating different amounts of glycerol during membrane preparation. Under optimal conditions, the asymmetric PES membrane made with 1.2 wt% of glycerol (PES-G1.2) possesses a thin skin layer with a uniform nanopore distribution, which is ideal for regulating the ion flux near the Li anode surface, thus suppressing Li dendrite formation. Our results demonstrate that the PES-G1.2 possesses exceptional ionic conductivity of 1.76 mS cm−1, Li+ transference number of 0.52, and high compatibility with Li electrode. Additionally, the Li/PES-G1.2/LiFePO4 cells also present a remarkable rate capability with specific capacity of 150 mAh g−1 at 0.2 C and 81 mAh g−1 at 10 C, respectively, and 90 % of capacity can be retained after 100 charge-discharge cycles under 0.2 C. These findings shed light on the unique properties of asymmetric porous membrane as well as its promising potential for applications in lithium metal batteries.

The instant powder of Ejiao, vigna angularis and semen coicis (IPEVS) were prepared with Ejiao Low Mol.Wt. Peptid, vigna angularis and semen coicis as main raw materials, maltodextrin, xylitol and β-cyclodextrin as auxiliary materials. The effects of processing technology of raw material powder and the amount of excipients on IPEVS were tested by single factor and response surface method. The results showed that the optimum technological conditions were as follows: the ratio of vigna angularis to semen coicis was 1∶1, baking time was 50 min, baking temperature was 120 ℃, the addition amount of Ejiao Low Mol.Wt. Peptid was 4%, maltodextrin was 24%, xylitol was 10%, β-cyclodextrin was 9%. Under this condition, the wettability of IPEVS was 129 s, the dispersibility was 5 s, and it had good taste and toning property. The moisture content is 2.3%, the protein content is 13%, the content of polysaccharide is 47%, the total number of colony is less than 3 000 cfu/g, the number of coliform is less than 90 MPN/100 g, which accords with the national requirement.

Abstract Alzheimer’s disease (AD) pathology and amyloid-beta (Aβ) plaque deposition progress slowly in the cerebellum compared to other brain regions, while the entorhinal cortex (EC) is one of the most vulnerable regions. Using a knock-in AD mouse model (App KI), we show that within the cerebellum, the deep cerebellar nuclei (DCN) has particularly low accumulation of Aβ plaques. To identify factors that might underlie differences in the progression of AD-associated neuropathology across regions, we profiled gene expression in single nuclei (snRNAseq) across all cell types in the DCN and EC of wild-type (WT) and App KI male mice at age 7 months. We found differences in expression of genes associated with inflammatory activation, PI3K–AKT signalling, and neuron support functions between both regions and genotypes. In WT mice, the expression of interferon-response genes in microglia is higher in the DCN than the EC and this enrichment is confirmed by RNA in situ hybridisation, and measurement of inflammatory cytokines by protein array. Our analyses also revealed that multiple glial populations are responsible for establishing this cytokine-enriched niche. Furthermore, homogenates derived from the DCN induced inflammatory gene expression in BV2 microglia. We also assessed the relationship between the DCN microenvironment and Aβ pathology by depleting microglia using a CSF1R inhibitor PLX5622 and saw that, surprisingly, the expression of a subset of inflammatory cytokines was increased while plaque abundance in the DCN was further reduced. Overall, our study revealed the presence of a cytokine-enriched microenvironment unique to the DCN that when modulated, can alter plaque deposition.

Abstract We investigate the functionality of NbOx-based selector devices on a flexible substrate. It was observed that the failure mechanism of cyclic tensile strain is from the disruption of atom arrangements, which essentially led to the crack formation of the film. When under cyclic compressive strain, buckling delamination of the film occurs as the compressed films have debonded from their neighboring layers. By implementing an annealing process after the strain-induced degradation, recovery of the device is observed with reduced threshold and hold voltages. The physical mechanism of the device is investigated through Poole–Frenkel mechanism fitting, which provides insights into the switching behavior after mechanical strain and annealing process. The result demonstrates the potential of the NbOx device in flexible electronics applications with a high endurance of up to 105 cycles of cyclic bending strain and the recovery of the device after degradation.

As a new resource food in China, acer truncatum seed oil is rich in oleic acid, linoleic acid and neuroic acid and other components, and their nutritional value and medicinal health care effects are prominent, which has been increasingly valued by the industry and consumers. In recent years, the new preparation and application development technology of Acer truncatum seed oil has been continuously presented. It has not only been developed for food, but also appeared successively in the flavoring of Acer truncatum seed oil, complex dairy products,tablet candy, etc. It has also been applied in the fields of daily chemical industry, medical care and so on. This paper reviewed the current research progress and the existing problems in the preparation, efficacy evaluation, industrial application and development, and putted forward some suggestions for these problems, which could promote the development and perfection of Acer truncatum seed oil industry.

Medium chain triglycerides has the effect of reducing body weight, regulating lipid metabolism, relieving fatigue and so on, and it is liquid at room temperature. In order to facilitate its application in the field of food, the medium chain triglycerides microcapsules were prepared by spray drying with whey protein and inulin as composite wall materials. The effects of composite wall material proportion, wall material addition amount, core-wall ratio, emulsifier addition amount and composite emulsifier proportion on the embedding rate of medium chain triglycerides microcapsules were investigated by single factor experiment. Box-Behnken design response surface test was used to optimize the preparation formula of medium chain triglycerides microcapsules, and the basic physical and chemical properties of the prepared medium chain triglyceride microcapsules were determined. The response surface method results showed that the optimal preparation conditions of medium chain triglycerides microcapsules were as follows: whey protein: inulin ratio of 3∶1 (w/w), emulsifier supplemental amount of 0.4 g/100 mL, core wall ratio of 1∶1 (w/w), compound wall material (whey protein and inulin) supplemental amount of 14 g/100 mL, compound emulsifier (monoglycerol∶sodium carboxymethyl cellulose) ratio of 1∶1 (w/w), under this condition, the embedding rate of carbon chain fatty acid triglyceride microcapsules can reach 95%. The medium chain triglycerides microcapsules had good fluidity, dispersibility and solubility. The microcapsules had uniform particle size, the average particle size were 4.43 μm.

Abstract Background The Polygonatum cyrtonema Hua rhizomes (also known as Rhizoma Polygonati, RP) are consumed for their health benefits. The main source of the RP is wild P. cyrtonema populations in the Hunan province of China. However, the soil Cadmium (Cd) content in Huanan is increasing, thus increasing the risks of Cd accumulation in RP which may end up in the human food chain. To understand the mechanism of Cd accumulation and resistance in P. cyrtonema, we subjected P. cyrtonema plants to four levels of Cd stress [(D2) 1, (D3) 2, (D4) 4, and (D5) 8 mg/kg)] compared to (D1) 0.5 mg/kg. Results The increase in soil Cd content up to 4 mg/kg resulted in a significant increase in tissue (root hair, rhizome, stem, and leaf) Cd content. The increase in Cd concentration variably affected the antioxidant enzyme activities. We could identify 14,171 and 12,115 protein groups and peptides, respectively. There were 193, 227, 260, and 163 differentially expressed proteins (DEPs) in D2, D3, D4, and D5, respectively, compared to D1. The number of downregulated DEPs increased with an increase in Cd content up to 4 mg/kg. These downregulated proteins belonged to sugar biosynthesis, amino acid biosynthesis-related pathways, and secondary metabolism-related pathways. Our results indicate that Cd stress increases ROS generation, against which, different ROS scavenging proteins are upregulated in P. cyrtonema. Moreover, Cd stress affected the expression of lipid transport and assembly, glycolysis/gluconeogenesis, sugar biosynthesis, and ATP generation. Conclusion These results suggest that an increase in soil Cd content may end up in Huangjing. Cadmium stress initiates expression changes in multiple pathways related to energy metabolism, sugar biosynthesis, and secondary metabolite biosynthesis. The proteins involved in these pathways are potential candidates for manipulation and development of Cd stress-tolerant genotypes.

The three macronutrients of lipid, protein and carbohydrate are closely related to human health, and their supply is basically sufficient. However, with the increasing number of patients suffered from hyperlipidemia, obesity, etc., as well as the deepening of the aging process, traditional nutrients can not fulfill the nutritional needs of these people anymore. Therefore, nutritional, processing and organoleptic properties of these three major nutrients need to be enhanced by the deep-processing. Nowadays, the recombinant protein and carbohydrate industries have made great progress in China, but the recombinant lipid industry is just in its infancy. Hence, this paper briefly introduced the status, development opportunities and challenges of domestic structure lipid industry，and expounded the underlying efficacy mechanisms of several main structure lipids. The latest research progress on the health effects and preparation technology of structure lipid were also presented. In addition, in view of the existing problems, future development advices are proposed from the perspectives of theoretical breakthrough, technological innovation, and industrial upgrading, aiming to provide valuable references for the development of domestic structure industry.

ObjectiveTo determine the characteristics of human immunodeficiency virus type 1 （HIV-1） subtypes among newly confirmed HIV-1 patients in Hongkou District of Shanghai， and provide evidence for establishing HIV-1 subtype database and precise prevention and control strategy against AIDS in Hongkou District of Shanghai.MethodsA total of 119 plasma samples from newly confirmed HIV-1 patients in Hongkou District in 2016 were used to detect HIV-1 RNA pol gene by using reverse transcription PCR. HIV-1 subtypes were determined with Los Alamos 2022 HIV-1 gene database using HIV-BLAST tool， and then characterized by epidemiological data.ResultsIn the 119 samples， a total of 89 pol gene fragments were obtained， which were mainly classified as CRF07_BC （38.2%）， CRF01_AE （36.0%）， and subtype B （13.5%）. Furthermore， two new recombinant subtype CRF55_01B and two unique recombinant subtype URF_0107 were identified （2.3%）.ConclusionIn 2016， HIV-1 subtypes in Hongkou District are mainly CRF07_BC and CRF01_AE. In addition， new recombinant subtype CRF55_01B and unique recombinant subtype URF_0107 have appeared in Hongkou District. It warrants a need of enhanced surveillance.

ObjectiveTo determine the HIV-1 subtypes and pre-treatment drug resistance （PDR） mutations in newly reported HIV-1-infected cases in Hongkou District of Shanghai， and provide evidence for the adjustment of antiretroviral therapy （ART）.MethodsA total of 119 plasma samples of newly reported HIV-1-infected cases were collected in Hongkou District， Shanghai. Nucleic acid extraction was conducted to obtain HIV-1 RNA， and an in-house method was performed to amplify the pol gene fragment using reverse transcription PCR. The pol gene was then sequenced. Subtypes and PDR mutations were determined using HIV BLAST and HIV drug resistance online databases.ResultsA total of 89 HIV-1 pol gene fragments were obtained. Among them， CRF07_BC， CRF01_AE， B subtypes， CRF08_BC， CRF55_01B， and URF0107 accounted for 38.20%， 35.96%， 13.48%， 7.87%， 2.25%， and 2.25%， respectively. There were 13 samples with drug resistance mutations， of which 3 mutations were related to protease inhibitors （PIs）， 9 mutations were related to non-nucleoside reverse transcriptase inhibitors （NNRTIs）， and 1 mutation was related to nucleoside reverse transcriptase inhibitors （NRTIs）. Furthermore， 7 （7.87%， 7/89） PDR mutations were identified， of which 2 were highly resistant， 1 was intermediately resistant and 4 were lowly resistant. Additionally， 2 （2.25%， 2/89） PDR mutations belonged to the surveillance drug resistance mutations （SDRMs） list and surveillance of transmitted drug resistant （STDR）， with mutation sites being M184V and K103N， respectively， which were predicted to be highly resistant to efavirenz， nevirapine， emtricitabine， and lamivudine.ConclusionSurveillance on HIV-1 subtype and drug resistance should be strengthened， to focus on certain recombinant subtypes and PDR mutations， especially the URF0107 recombinant subtype and the transmitted drug resistance mutations related to efavirenz， nevirapine， emtricitabine， and lamivudine.

Background and Objectives: Emotion regulation (ER) deficits are increasingly implicated in obsessive-compulsive symptoms (OCS). The ER difficulty of ‘non-acceptance of emotions’ has been most consistently found to correlate with OCS – albeit not uniformly with all OCS dimensions. This study examined the causal relationships between the acceptance of emotions and four OCS dimensions: contamination, responsibility of harm, unacceptable thoughts and symmetry. Methods: Participants in this online study rated their baseline emotional distress and compulsive urges to OC scenarios corresponding to each OCS dimension. After completing questionnaires on ER, OCS, anxiety and depressive symptoms, participants were randomly assigned to two conditions and instructed to observe and accept their emotions (acceptance condition; n = 180) or observe their emotions (control condition; n = 185) as they re-read the scenarios. Participants then rated their post-manipulation emotional distress and compulsive urges to each scenario. Results: The instructions to accept emotions resulted in lower compulsive urges to the responsibility of harm scenario, for participants with lower baseline compulsive urges. There were no other group differences on post-manipulation measures. Conclusions: The current findings suggest that even brief instructions to accept one’s emotions reduced compulsive urges, pointing to the potential clinical utility of enhancing the acceptance of emotions.

PurposeTo compare the effects of remimazolam and dexmedetomidine on early postoperative cognitive dysfunction (POCD) in aged gastric cancer patients.MethodsFrom June to December 2022, 104 elderly patients (aged 65–80 years) received laparoscopic radical resection of gastric cancer at the First Affiliated Hospital of Nanchang University. Using the random number table approach, the patients were separated into three groups: remimazolam (Group R), dexmedetomidine (Group D), and saline (Group C). The primary outcome was the incidence of POCD, and secondary outcomes included TNF-α and S-100β protein concentrations, hemodynamics, VAS scores, anesthesia recovery indicators, and the occurrence of adverse events within 48 h postoperatively.ResultsAt 3 and 7 days after surgery, there were no statistically significant differences in the incidence of POCD, the MMSE and MoCA scores between groups R and D (p > 0.05). However, compared to the saline group, both groups had higher MMSE and MoCA scores and decreased incidences of POCD. These differences were statistically significant (p 0.05) in the levels of TNF-α and S-100β protein at the three time points (at the end of the surgery, 1 day later, and 3 days later). Even though neither group’s concentration of the two factors was as high as that of the saline group, the differences were statistically significant (p group R > group D. Extubation and PACU residence times did not differ statistically significantly (p > 0.05) between the three groups. There was no significant difference in VAS scores between groups R and D after 24 h postoperatively (p > 0.05), although both had lower scores than group C, and the difference was statistically significant (p 0.05). Adverse reactions such as respiratory depression, hypotension, bradycardia, agitation, drowsiness, and nausea and vomiting had the lowest incidence in group R and the highest incidence in group C (p

In this study, Spoilage of salmon was investigated using electrochemical impedance spectroscopy (EIS) and terahertz time-domain spectroscopy (TDS). Salmon tissues were continuously observed for more than 20 h, from fresh to full spoilage. The complex impedance (Z) and phase shift (θ) of the salmon samples were derived based on the EIS signal. Critical frequency changes, phase shifts, and impedance variations with time at different frequencies were extracted from the data and used as indicators of the freshness of salmon. In the THz TDS analysis, time-domain spectra were recorded in transmission and reflection modes. Four stages of fish spoilage were clearly observed in both the EIS and THz TDS spectra. Although EIS is more sensitive under the current experimental conditions, THz TDS in reflection mode provides a non-invasive and non-destructive way to monitor salmon spoilage, which is practically beneficial for the food quality control industry.

Dynamical controls on terahertz (THz) wavefronts are crucial for many applications, but available mechanism requests tunable elements with sub-micrometer sizes that are difficult to find in the THz regime. Here, different from the local-tuning mechanism, we propose an alternative approach to construct wavefront-control meta-devices combining specifically designed metasurfaces and globally tuned graphene layers. Coupled-mode-theory (CMT) analyses reveal that graphene serves as a tunable loss to drive the whole meta-device to transit from one functional phase to another passing through an intermediate regime, exhibiting distinct far-field (FF) reflection wavefronts. As a proof of concept, we design/fabricate a graphene meta-device and experimentally demonstrate that it can reflect normally incident THz wave to pre-designed directions with different polarizations under appropriate gating voltages. We finally design a graphene meta-device and numerically demonstrate that it can generate vectorial THz beams with continuously varying polarization distributions upon gating. These findings pave the road to realizing a wide range of THz applications, such as sensing, imaging, and wireless communications.

Abstract This study aimed to describe the topographic variation of the macula’s choroidal angioarchitecture using three-dimensional (3D) choroidal vascularity index (CVI) of healthy eyes from an Asian population and to investigate the associations of CVI. 50 participants were recruited via stratified randomisation based on subfoveal choroidal thickness from the Singapore Epidemiology of Eye Diseases Study. Macular volume scans were acquired using spectral-domain optical coherence tomography with enhanced depth imaging. CVI was assessed based on B-scan binarisation and choroid segmentation. The 3D CVI of the whole, superior, central, and inferior macula were 62.92 ± 1.57%, 62.75 ± 1.93%, 63.35 ± 1.72%, and 62.66 ± 1.70%, respectively, pairwise comparisons P all > 0.05). 3D CVI (Whole Macula) and 2D CVI (Subfoveal) were associated only with each other and not with other ocular and systemic factors. 2D CVI (Subfoveal) had a moderate agreement with 3D CVI (Central Macula) [intraclass corelation coefficient (ICC) = 0.719], and had poorer agreement with 3D CVI of the whole macula, superior, and inferior macula (ICC = 0.591, 0.483, and 0.394, respectively). Scanning volume did not influence 3D CVI measurements. In conclusion, 3D CVI demonstrated no significant topographic variation. CVI was not correlated with demographic or ocular structural features. 2D CVI of the fovea is partially representative of 3D CVI of the macula.

Objectives: Despite the availability of cancer rehabilitation, utilization at our institution was low. We designed the Cancer Rehabilitation Questionnaire (CRQ) to investigate the prevalence of functional impairments amongst cancer survivors and attitudes towards rehabilitation participation. We evaluated the performance of CRQ as a screening tool for detecting clinically important physical dysfunction. Design: A cross-sectional study was performed, recruiting cancer survivors at a university outpatient oncology clinic. Cancer survivors completed the CRQ and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire – Core 30 Questionnaires. Descriptive statistical analysis and receiver operator characteristics analysis were performed to assess the ability of the CRQ to detect clinically important physical dysfunction, as measured by the EORTC QLQ-C30. Results: Of 204 participants, 87.3% reported impairments in at least 1 CRQ domain. Pain and weakness were most common. The number of positive items correlated with EORTC global health status and functional scales. A cut-off of ≥ 4 on the CRQ predicted clinically important physical dysfunction (sensitivity 61.8%, specificity 75.5%). Of those with impairments, 53.9% were unwilling to participate in rehabilitation. Transportation, need for caregivers, and cost were the main barriers. Conclusion: Our findings will guide resource allocation to overcome barriers to participation. The CRQ can help to stratify cancer survivors requiring further rehabilitation interventions. LAY ABSTRACT Functional impairments due to cancer and its treatment are common, and can be effectively addressed with rehabilitation. To better provide cancer rehabilitation, the Cancer Rehabilitation Questionnaire was designed to investigate what functional problems cancer survivors have and their attitudes towards participation in rehabilitation. We compared the cancer rehabilitation questionnaire with the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) to see if it could be used as a screening tool for rehabilitation needs. Of 204 participants, 87.3% reported functional impairments in at least 1 Cancer Rehabilitation Questionnaire domain. Pain and weakness were most common. The number of positive Cancer Rehabilitation Questionnaire items correlated with EORTC scales: ≥ 4 positive items in the Cancer Rehabilitation Questionnaire indicated that the number of physical impairments was clinically significant. Among participants with impairments, 53.9% were unwilling to participate in rehabilitation. Transportation, need for caregivers, and cost were cited as barriers. A simple screening tool, such as the Cancer Rehabilitation Questionnaire can help to stratify cancer patients requiring further rehabilitation and intervention.

Inter-patient and intra-tumour heterogeneity (ITH) have prompted the need for a more personalised approach to cancer therapy. Although patient-derived xenograft (PDX) models can generate drug response specific to patients, they are not sustainable in terms of cost and time and have limited scalability. Tumour Organ-on-Chip (OoC) models are in vitro alternatives that can recapitulate some aspects of the 3D tumour microenvironment and can be scaled up for drug screening. While many tumour OoC systems have been developed to date, there have been limited validation studies to ascertain whether drug responses obtained from tumour OoCs are comparable to those predicted from patient-derived xenograft (PDX) models. In this study, we established a multiplexed tumour OoC device, that consists of an 8 × 4 array (32-plex) of culture chamber coupled to a concentration gradient generator. The device enabled perfusion culture of primary PDX-derived tumour spheroids to obtain dose-dependent response of 5 distinct standard-of-care (SOC) chemotherapeutic drugs for 3 colorectal cancer (CRC) patients. The in vitro efficacies of the chemotherapeutic drugs were rank-ordered for individual patients and compared to the in vivo efficacy obtained from matched PDX models. We show that quantitative correlation analysis between the drug efficacies predicted via the microfluidic perfusion culture is predictive of response in animal PDX models. This is a first study showing a comparative framework to quantitatively correlate the drug response predictions made by a microfluidic tumour organ-on-chip (OoC) model with that of PDX animal models.

PurposesPediatric open cardiac surgical patients usually suffer from acute pain after operation. The current work aimed to explore the impact of bilateral PIFB in children suffering from open cardiac surgery.MethodsThis work randomized altogether 110 child patients as bilateral PIFB (PIF) and non-nerve block (SAL) groups. This work adopted post-operative pain at exercise and rest statuses as the primary endpoint, whereas time-to-drain removal/extubation/initial defecation, intraoperative/post-operative fentanyl use, and length of ICU and hospital stay as the secondary endpoints.ResultsMOPS were significantly higher at 24-h post-operatively at coughing and rest statuses in SAL group compared with PIF group. Meanwhile, PIF group exhibited markedly lower intraoperative/post-operative fentanyl use amounts, as well as markedly reduced time-to-extubation/initial flatus, and length of ICU/hospital stay.ConclusionBilateral PIFB in pediatric open cardiac surgical patients provide effective analgesia and lower the length of hospital stay.

Chemoresistance is one of the main challenges for cancer therapy success. Here, the authors show that dual-specificity phosphatase 16 (DUSP16) expression is associated with chemoresistance in several types of cancer through impairing mitochondria-associated apoptosis.

Purpose: To evaluate differences in the retinal microvasculature and structure and choroidal structure among men and women with Alzheimer’s disease (AD) compared with age-matched cognitively normal male and female controls. Design: Case-control study of participants ≥ 50 years of age. Participants: A total of 202 eyes of 139 subjects (101 cases and 101 controls). Methods: All participants and controls underwent OCT and OCT angiography (OCTA), and parameters of subjects with AD were compared with those of cognitively normal controls. Main Outcome Measures: The foveal avascular zone (FAZ) area, vessel density (VD), and perfusion density (PD) in the superficial capillary plexus within the 3- and 6-mm circle and ring using Early Treatment Diabetic Retinopathy Study (ETDRS) grid overlay on OCTA; central subfield thickness (CST), retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT. Results: No significant sex differences in VD or PD were found in the AD or control cohorts; however, there were greater differences in VD and PD among AD female participants than AD male participants compared with their respective controls. The CST and FAZ area were not different between male and female AD participants. Among controls, men had a thicker CST (P < 0.001) and smaller FAZ area (P = 0.003) compared with women. The RNFL thickness, GCIPL thickness, and CVI were similar among male and female AD participants and controls. Conclusions: There may be a loss of the physiologic sex-related differences in retinal structure and microvasculature in those with AD compared with controls. Further studies are needed to elucidate the pathophysiological basis for these findings.

Purpose: Preoperative carbohydrate loading (CHO) could improve insulin sensitivity and promoted postoperative recovery under general anesthesia. The aim of this study was to investigate the effects of CHO on gynecological patients. Methods: A group of 58 female patients undergoing surgery were randomized to either fast overnight (the FAST group) or receive 800 ml of CHO the evening before and 400 ml 2 h before anesthesia (the CHO group).The perioperative well-being and the nutritional status, as determined by blood samples for three biochemical assays (the base status, the status after the operation, and the status on the first day after the operation), were recorded. The homeostasis model assessment (HOMA-IR) was used to measure perioperative insulin resistance. The primary endpoint was phantom limb syndrome (PLS) induced by combined spinal and epidural anesthesia (CSEA). Results: The CHO group had significantly lower levels of anxiety (p

Neurological diseases including stroke and neurodegenerative disorders cause a hefty burden on the healthcare system. Survivors experience significant impairment in mobility and daily activities, which requires extensive rehabilitative interventions to assist them to regain lost skills and restore independence. The advent of remote rehabilitation architecture and enabling technology mandates the elaboration of sensing mechanisms tailored to individual clinical needs. This study aims to review current trends in the application of sensing mechanisms in remote monitoring and rehabilitation in neurological diseases, and to provide clinical insights to develop bespoke sensing mechanisms. A systematic search was performed using the PubMED database to identify 16 papers published for the period between 2018 to 2022. Teleceptive sensors (56%) were utilized more often than wearable proximate sensors (50%). The most commonly used modality was infrared (38%) and acceleration force (38%), followed by RGB color, EMG, light and temperature, and radio signal. The strategy adopted to improve the sensing mechanism included a multimodal sensor, the application of multiple sensors, sensor fusion, and machine learning. Most of the stroke studies utilized biofeedback control systems (78%) while the majority of studies for neurodegenerative disorders used sensors for remote monitoring (57%). Functional assessment tools that the sensing mechanism may emulate to produce clinically valid information were proposed and factors affecting user adoption were described. Lastly, the limitations and directions for further development were discussed.

An important non-structural solution in flood management is susceptibility mapping, which identifies the likelihood of flood occurrence in an area. Although various models have been applied in flood susceptibility mapping with different successes, Geographically Weighted Regression [GWR] has not been sufficiently tested despite its effective advantages in interpreting spatially heterogeneous relationships. To test GWR's effectiveness in flood susceptibility modelling, this study included 16 morphometric parameters as the explanatory variables, and historical flood occurrence as the dependent. Multicollinearity was eliminated based on Variance Inflation Factor [VIF], which resulted in six screened parameters: stream order, drainage texture, relief ratio, bifurcation ratio, topographic wetness index, and topographic position index. Five tests were carried out, with the first involving direct inputs of the VIF-screened variables into the GWR modelling process. The other four tests incorporated morphometric parameter normalisation into 1-to-5 ranking scores according to Ordinary Least Square [OLS] coefficients or literature using all or only the VIF-screened parameters. The best-performing model was the first test, indicating that direct input of the screened parameters was the ideal modelling process. This test had the lowest corrected Akaike Information Criterion (160.01), the highest percentage of deviance explained (46.18%), lowest spatial autocorrelation of residuals (0.1122) and transformed residuals (0.2827), highest success accuracy (91.24%), and second-best prediction accuracy (75.15%). These findings show that accounting for spatial variation improved global flood model performance. The results also show that GWR may have the potential for better flood susceptibility mapping when compared with other traditional models such as non-spatial logistic regression and frequency ratio.

Salvianic acid A (SAA), as the main bioactive component of the traditional Chinese herb Salvia miltiorrhiza, has important application value in the treatment of cardiovascular diseases. In this study, a two-step bioprocess for the preparation of SAA from l-DOPA was developed. In the first step, l-DOPA was transformed to 3,4-dihydroxyphenylalanine (DHPPA) using engineered Escherichia coli cells expressing membrane-bound L-amino acid deaminase from Proteus vulgaris. After that, the unpurified DHPPA was directly converted into SAA by permeabilized recombinant E. coli cells co-expressing d-lactate dehydrogenase from Pediococcus acidilactici and formate dehydrogenase from Mycobacterium vaccae N10. Under optimized conditions, 48.3 mM of SAA could be prepared from 50 mM of l-DOPA, with a yield of 96.6%. Therefore, the bioprocess developed here was not only environmentally friendly, but also exhibited excellent production efficiency and, thus, is promising for industrial SAA production.

Objectives 3D-printed (3DP) customized temporary cranial protection solutions following decompressive craniectomy (DC) are currently not widely practiced. A pilot trial of a 3DP customized head protection prototype device (HPPD) on 10 subjects was conducted during the subacute rehabilitation phase. Materials and methods Subjects > 30 days post-DC with stable cranial flaps and healed wounds were enrolled. HPPD were uniquely designed based on individuals’ CT scan, where the base conformed to the surface of the individual’s skin covering the cranial defect, and the lateral surface three-dimensionally mirrored, the contralateral healthy head. Each HPPD was fabricated using the fused deposition modeling method. These HPPD were then fitted on subjects using a progressive wearing schedule and monitored over 1, 2, 4, 6 and 8 follow-up (FU) weeks. Outcomes during FU included; reported wearing time/day (hours), subjective pain, discomfort, pruritus, dislodgment, cosmesis ratings; and observed wound changes. The primary outcome was safety and tolerability without pain or wound changes within 30 minutes of HPPD fitting. Results In all, 10 enrolled subjects received 12 HPPDs [5/10 male, mean (SD) age 46 (14) years, mean (SD) duration post-DC 110 days (76)] and all subjects tolerated 30 minutes of initial HPPD fitting without wound changes. The mean (SD) HPPD mass was 61.2 g (SD 19.88). During 8 weeks of FU, no HPPD-related skin dehiscence was observed, while 20% (2/10) had transient skin imprints, and 80% (8/10) reported self-limiting pressure and pruritis. Discussion Findings from this exploratory study demonstrated preliminary feasibility and safety for a customized 3DP HPPD for temporary post-DC head protection over 8 weeks of follow-up. Monitoring and regular rest breaks during HPPD wear were important to prevent skin complications. Conclusion This study suggests the potential for wider 3DP technology applications to provide cranial protection for this vulnerable population.

We describe the clinical, laboratory and radiological features of 3 critically ill patients with COVID-19 who developed severe encephalopathy. The first patient did not regain consciousness when sedation was removed at the end of 2 weeks of intensive care. He had received treatment with convalescent plasma. His clinical examination was remarkable for intact brainstem reflexes, roving eye movements, later transient ocular flutter; and then what appeared to be slow ocular dipping. He had no coherent volitional response to the environment. The second patient recovered with measurable cognitive deficits after a prolonged period of encephalopathy. He had received combination treatment with interferon beta 1b and lopinavir/ritonavir. The third patient remained in persistent, severe agitated delirium and died 3 months into his illness. The MRI of the 3 patients showed multifocal abnormalities predominantly in the cerebral white matter, with varying involvement of the grey matter, brainstem and spinal cord. Case 1's MRI changes were consistent with acute disseminated encephalomyelitis. The patients also displayed blood markers, to varying degree, of autoimmunity and hypercoagulability. We were not able to convincingly show, from microbiological as well as immunological evaluation, if the effects of COVID-19 on these patients' nervous system were a direct consequence of the virus, proinflammatory-thrombotic state or a combination. Patient 1 responded partially to empirical, albeit delayed, therapy with intravenous immunoglobulins. Patient 2 recovered with no specific treatment. These cases illustrate the need to understand the full spectrum of encephalopathy associated with COVID-19 so as to better guide its management.

Background: Medical professionalism enhances doctor-patient relationships and advances patient-centric care. However, despite its pivotal role, the concept of medical professionalism remains diversely understood, taught and thus poorly assessed with Singapore lacking a linguistically sensitive, context specific and culturally appropriate assessment tool. A scoping review of assessments of professionalism in medicine was thus carried out to better guide its understanding. Methods: Arksey and O’Malley’s (2005) approach to scoping reviews was used to identify appropriate publications featured in four databases published between 1 January 1990 and 31 December 2018. Seven members of the research team employed thematic analysis to evaluate the selected articles. Results: 3799 abstracts were identified, 138 full-text articles reviewed and 74 studies included. The two themes identified were the context-specific nature of assessments and competency-based stages in medical professionalism. Conclusions: Prevailing assessments of professionalism in medicine must contend with differences in setting, context and levels of professional development as these explicate variances found in existing assessment criteria and approaches. However, acknowledging the significance of context-specific competency-based stages in medical professionalism will allow the forwarding of guiding principles to aid the design of a culturally-sensitive and practical approach to assessing professionalism.

Background: Growing concerns over ethical issues in mentoring in medicine and surgery have hindered efforts to reinitiate mentoring for Palliative Care (PC) physicians following the easing of COVID-19 restrictions. Ranging from the misappropriation of mentee’s work to bullying, ethical issues in mentoring are attributed to poor understanding and structuring of mentoring programs, underlining the need for a consistent approach to mentoring practices. Methods: Given diverse practices across different settings and the employ of various methodologies, a novel approach to narrative reviews (NR)s is proposed to summarize, interpret, and critique prevailing data on novice mentoring. To overcome prevailing concerns surrounding the reproducibility and transparency of narrative reviews, the Systematic Evidenced Based Approach (SEBA) adopts a structured approach to searching and summarizing the included articles and employed concurrent content and thematic analysis that was overseen by a team of experts. Results: A total of 18 915 abstracts were reviewed, 62 full text articles evaluated and 41 articles included. Ten themes/categories were ascertained identified including Nature; Stakeholders; Relationship; Approach; Environment; Benefits; Barriers; Assessments; Theories and Definitions. Conclusion: By compiling and scrutinizing prevailing practice it is possible to appreciate the notion of the mentoring ecosystem which sees each mentee, mentor, and host organization brings with them their own microenvironment that contains their respective goals, abilities, and contextual considerations. Built around competency based mentoring stages, it is possible to advance a flexible yet consistent novice mentoring framework.

Colorectal cancer (CRC) is a major cause of human death. Mortality is primarily due to metastatic organ colonization, with the liver being the main organ affected. We modeled metastatic CRC (mCRC) liver colonization using patient-derived primary and metastatic tumor xenografts (PDX). Such PDX modeling predicted patient survival outcomes. In vivo selection of multiple PDXs for enhanced metastatic colonization capacity upregulated the gluconeogenic enzyme PCK1, which enhanced liver metastatic growth by driving pyrimidine nucleotide biosynthesis under hypoxia. Consistently, highly metastatic tumors upregulated multiple pyrimidine biosynthesis intermediary metabolites. Therapeutic inhibition of the pyrimidine biosynthetic enzyme DHODH with leflunomide substantially impaired CRC liver metastatic colonization and hypoxic growth. Our findings provide a potential mechanistic basis for the epidemiologic association of anti-gluconeogenic drugs with improved CRC metastasis outcomes, reveal the exploitation of a gluconeogenesis enzyme for pyrimidine biosynthesis under hypoxia, and implicate DHODH and PCK1 as metabolic therapeutic targets in CRC metastatic progression.

Abstract The preservation of nucleic acids from clinical samples is critical to facilitate accurate molecular diagnosis. The use of a paper matrix, Flinders Technology Associates (FTA) Elute cards, to archive DNA and viral RNA is well-documented. However, the feasibility of FTA Elute cards for archiving serum and serum exosomal microRNAs (miRNAs) remains unclear. Here, we performed a comprehensive evaluation of FTA Elute cards for miRNA storage and recovery in different pre-analytical conditions. The recovery of serum miRNA dry-spotted on FTA Elute cards by direct elution with water at high temperature was poor. However, serum miRNAs dry-spotted on the cards were isolated with about 40% yield when using QIAzol lysis reagent and recovery was improved remarkably (>80%) upon extraction from cards pre-treated with trehalose. miRNAs stored on the cards remained stable at room temperature and can be kept for prolonged periods. Furthermore, miRNAs could be similarly recovered from serum exosomes dry-spotted on the cards. Importantly, when using sera from gastric cancer (GC) patients, the miRNAs were efficiently recovered from trehalose pre-treated cards without affecting their representation. Collectively, we have demonstrated the potential of FTA Elute cards to archive serum and serum exosomal miRNAs, making it useful for biomarker discovery and diagnostics.

Summary Severe hypoglycaemia carries considerable morbidity and potential mortality. We aim to elucidate the factors which were associated with a prolonged length of stay (LOS) among patients with diabetes who were admitted to the hospital with severe hypoglycaemia. Three hundred and four patients were included in the analysis, with a mean age of 70.6 ± 11.3 years, mean glycated haemoglobin of 6.9 ± 1.3% and median LOS of 3 days. Patients with a LOS >3 days had significantly higher Charlson Comorbidity Index (CCI) (4.9 ± 2.1 vs 4.1 ± 2.1, P