Integrated Microfluidic-Transistor Sensing System for Multiplexed Detection of Traumatic Brain Injury Biomarkers.

Traumatic brain injury (TBI) is widely recognized as a global public health crisis, affecting millions of people each year, leading to permanent neurologic, emotional, and occupational disability, and highlighting the urgent need for rapid, sensitive, and early assessment. Here, we design a novel and simple lithography-free method for preparing dual-channel graphene-based field-effect transistors (G-FETs) and integrating them with microfluidic channels for simultaneously multiplexed detection of key blood TBI biomarkers: neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP). The G-FET utilizes an ingenious dual-channel electrode array design, where the source is shared between channels and the drains are independent of each other, which is the key to achieving simultaneous output of dual detection signals. At the same time, the microfluidic chip realizes microscale fluidic control and fast sample response time. This integrated detection system shows excellent sensitivity in biological fluids for the TBI biomarkers with detection limits as low as 55.63 fg/mL for NFL and 144.45 fg/mL for GFAP in phosphate-buffered saline (PBS) buffer, respectively. Finally, the clinical sample analysis shows promising performance for TBI detection, with an area under the curve (AUC) of 0.98 for the two biomarkers. And the combined dual-protein assay is also a good predictor of intracranial injury findings on computed tomography (CT) scans (AUC = 0.907). The integrated microfluidic G-FET device with a dual-signal output strategy has important potential for application in clinical practice, providing more comprehensive information for brain injury assessment.

Monoclonal Antibodies as a Therapeutic Strategy against Multidrug-Resistant Bacterial Infections in a Post-COVID-19 Era.

The development of severe multidrug-resistant bacterial infections has recently intensified because of the COVID-19 pandemic. According to the guidelines issued by the World Health Organization (WHO), routine antibiotic administration is not recommended for patients with supposed or confirmed mild SARS-CoV-2 infection or pneumonia, unless bacterial infection is clinically suspected. However, recent studies have pointed out that the proportion of non-essential antibiotic use in patients infected with SARS-CoV-2 remains high. Therefore, the silent pandemic of antibiotic resistance remains a pressing issue regardless of the present threats presented by the COVID-19 pandemic. To prevent or delay entry into the postulated post-antibiotic era, the long-term advocacy for the rational use of antibiotics, the optimization of infection control procedures, and the development of new antibacterial agents and vaccines should be underscored as vital practices of the antibacterial toolbox. Recently, the development of vaccines and monoclonal antibodies has gradually received attention following the advancement of biotechnology as well as enhanced drug discovery and development in cancer research. Although decent progress has been made in laboratory-based research and promising results have been obtained following clinical trials of some of these products, challenges still exist in their widespread clinical applications. This article describes the current advantages of antibacterial monoclonal antibodies, the development of associated clinical trials, and some perceived future perspectives and challenges. Further, we anticipate the development of more therapeutic agents to combat drug-resistant bacterial infections as well as to increase the resilience of current or novel agents/strategies.

Performance of the digital cell morphology analyzer MC-100i in a multicenter study in tertiary hospitals in China.

BACKGROUND: This study investigated the performance of the MC-100i, a pre-commercial digital morphology analyzer utilizing a convolutional neural network algorithm, in a multicentric setting involving up to 11 tertiary hospitals in China. METHODS: Blood smears were analyzed by MC-100i, verified by morphologists, and manually differentiated. The classification performance on WBCs and RBCs was evaluated by comparing the classification results using different methods. The PLT and PLT clump counting performance was also assessed. The total assay time including hands-on time was evaluated. RESULTS: The agreements between pre- and post-classification were high for normal WBCs (κ > 0.96) and lower for overall abnormal WBCs (κ = 0.90). The post-classification results correlated well with manual differentials for both normal and abnormal WBCs (r > 0.93), except for basophils (r = 0.8480) and atypical lymphocytes (r = 0.8211). The clinical sensitivity and specificity of each RBC abnormality after verification were above 90 % using microscopy reviews as the reference. The PLTs counted by the MC-100i before and after verification correlated well with those measured by the PLT-O mode (r = 0.98). Moreover, PLT clumps were successfully classified by the analyzer in EDTA-dependent pseudothrombocytopenia blood samples. CONCLUSIONS: The MC-100i is an accurate and reliable digital cell morphology analyzer, offering another intelligent option for hematology laboratories.

Characteristics and outcome of systemic treatment for metastatic or unresectable thymic carcinoma: A single institution experience.

BACKGROUND: Thymic carcinoma is a rare disease with an incidence of around 0.5 cases per million with a poor prognosis. The aim of this study was to assess patient outcomes with advanced thymic carcinoma receiving first-line chemotherapy. METHODS: In our retrospective cohort study, we included patients who underwent treatment for metastatic thymic carcinoma between January 2013 to December 2019 in our hospital. Overall survival, progression-free survival (PFS), objective response rates (ORR) and chemotherapy regimens were assessed and analyzed. RESULTS: A total of 27 patients were retrospectively analyzed. All patients received a platinum (cisplatin or carboplatin) based regimen as first-line chemotherapy (29.6% received ADOC, 11.1% received PE, 40.7% received CP, 14.8% received CAP). The median PFS on first-line chemotherapy was 199 days. The response rate was 40.7%. Median overall survival (OS) was 585 days. Positive CD5 staining was associated with better PFS. CONCLUSION: We highlight the critical role of platinum-based chemotherapy agents as a primary treatment modality in advanced thymic carcinoma, underscoring the efficacy of platinum as a first-line option for recurrent disease, even in cases previously treated with platinum. Additionally, our findings indicate that CD5 positivity could be associated with improved PFS, suggesting its potential as a prognostic marker.

Elizabethkingia anophelis outer membrane vesicles as a novel vaccine candidate against infection: insights into immune response and potential for passive immunity.

IMPORTANCE: Elizabethkingia anophelis, a Gram-negative pathogen, causes infections such as bacteraemia, pneumonia, and neonatal meningitis. The pathogen resists most antimicrobial classes, making novel approaches urgently needed. In natural settings, Gram-negative bacteria secrete outer membrane vesicles (OMVs) that carry important molecules in the bacterial life cycle. These OMVs are enriched with proteins involved in virulence, survival, and carbohydrate metabolism, making them a promising source for vaccine development against the pathogen. This study investigated the efficacy of imipenem-induced OMVs (iOMVs) as a vaccine candidate against E. anophelis infection in a mouse pneumonia model. Mice immunized with iOMVs were completely protected during lethal-dose challenges. Passive immunization with hyperimmune sera and splenocytes conferred protection against lethal pneumonia. Further investigation is needed to understand the mechanisms underlying the protective effects of iOMV-induced passive immunity, such as the action on specific antibody subclasses or T cell subsets.

Protocol for constructing GQD-PMO functionalized FET-biosensor for ultrasensitive exosomal miRNA detection.

Here, we present a protocol for constructing an ultrasensitive biosensor for exosomal-miRNA detection. We describe steps for preparing graphene quantum dot-phosphorodiamidate morpholino oligomer hybrids, depositing them onto the reduced graphene oxide field surface, hybridizing analyte miRNA with the sensor probe, and capturing and calculating electrical signals. We also detail procedures for optimizing biosensor construction and evaluating performance. By quantifying plasma exosomal miRNA21, this protocol can identify cancer patients from healthy individuals. For complete details on the use and execution of this protocol, please refer to Li et al.1.

Prenatal lipopolysaccharide exposure induces anxiety-like behaviour in male mouse offspring and aberrant glial differentiation of embryonic neural stem cells.

BACKGROUND: Prenatal infection has been implicated in the development of neuropsychiatric disorders in children. We hypothesised that exposure to lipopolysaccharide during prenatal development could induce anxiety-like behaviour and sensorineural hearing loss in offspring, as well as disrupt neural differentiation during embryonic neural development. METHODS: We simulated prenatal infection in FVB mice and mouse embryonic stem cell (ESC) lines, specifically 46C and E14Tg2a, through lipopolysaccharide treatment. Gene expression profiling analyses and behavioural tests were utilized to study the effects of lipopolysaccharide on the offspring and alterations in toll-like receptor (TLR) 2-positive and TLR4-positive cells during neural differentiation in the ESCs. RESULTS: Exposure to lipopolysaccharide (25 µg/kg) on gestation day 9 resulted in anxiety-like behaviour specifically in male offspring, while no effects were detected in female offspring. We also found significant increases in the expression of GFAP and CNPase, as well as higher numbers of GFAP + astrocytes and O4+ oligodendrocytes in the prefrontal cortex of male offspring. Furthermore, increased scores for genes related to oligodendrocyte and lipid metabolism, particularly ApoE, were observed in the prefrontal cortex regions. Upon exposure to lipopolysaccharide during the ESC-to-neural stem cell (NSC) transition, Tuj1, Map2, Gfap, O4, and Oligo2 mRNA levels increased in the differentiated neural cells on day 14. In vitro experiments demonstrated that lipopolysaccharide exposure induced inflammatory responses, as evidenced by increased expression of IL1b and ApoB mRNA. CONCLUSIONS: Our findings suggest that prenatal infection at different stages of neural differentiation may result in distinct disturbances in neural differentiation during ESC-NSC transitions. Furthermore, early prenatal challenges with lipopolysaccharide selectively induce anxiety-like behaviour in male offspring. This behaviour may be attributed to the abnormal differentiation of astrocytes and oligodendrocytes in the brain, potentially mediated by ApoB/E signalling pathways in response to inflammatory stimuli.

Modified Experimental Conditions for Noise-Induced Hearing Loss in Mice and Assessment of Hearing Function and Outer Hair Cell Damage.

An animal model of noise-induced hearing loss (NIHL) is useful for pathologists, therapists, pharmacologists, and hearing researchers to thoroughly understand the mechanism of NIHL, and subsequently optimize the corresponding treatment strategies. This study aims to create an improved protocol for developing a mouse model of NIHL. Male C57BL/6J mice were used in this study. Unanesthetized mice were exposed to loud noises (1 and 6 kHz, presented simultaneously at 115-125 dB SPL-A) continuously for 6 h per day for 5 consecutive days. Auditory function was assessed 1 day and 1 week after noise exposure, using auditory brainstem response (ABR). After the ABR measurement, the mice were sacrificed, and their organs of Corti were collected for immunofluorescence staining. From the auditory brainstem response (ABR) measurements, significant hearing loss was observed 1 day after noise exposure. After 1 week, the hearing thresholds of the experimental mice decreased to ~80 dB SPL, which was still a significantly higher level than the control mice (~40 dB SPL). From the results of immunofluorescence imaging, outer hair cells (OHCs) were shown to be damaged. In summary, we created a model of NIHL using male C57BL/6J mice. A new and simple device for generating and delivering pure-tone noise was developed and then employed. Quantitative measurements of hearing thresholds and morphological confirmation of OHC damage both demonstrated that the applied noise successfully induced an expected hearing loss.

The effect of economic growth pressure on green technology innovation: Do environmental regulation, government support, and financial development matter?

Green technology improvement is critical in promoting green development and mitigating negative externalities. Exploring the effect of economic growth pressure (EGP) on green technology innovation (GTI) is important for coordinated economic growth and green transformation. Using the data from 285 cities in China during 2006-2018, this study investigates the influence of EGP on GTI by taking the difference between economic growth target and previous year's actual growth rate to represent the EGP. The results indicate that EGP negatively affects GTI. When there is a 1% increase in EGP, green patent applications will fall by 3.2%. Furthermore, the heterogeneity analysis indicates that the negative effect of EGP is especially significant in western China compared with eastern and central regions. In addition, we find various nonlinear moderating effects between EGP and GTI by using panel threshold model. Specifically, EGP and GTI show an inverted U-shaped relationship with EGP increasing. Meanwhile, only when environmental regulation, government support, and financial development cross the thresholds will EGP have a significant role in promoting GTI. This study provides helpful implications for decision-makers to adopt a more reasonable combination of policy tools to achieve economic growth targets and low-carbon transformation.

Early cholecystectomy following percutaneous transhepatic gallbladder drainage is effective for moderate to severe acute cholecystitis in the octogenarians.

BACKGROUND: Acute cholecystitis (AC) is a life-threatening infectious/inflammatory disease in older patients. This study aimed to investigate the safety and optimal timing of surgery in patients aged ≥ 80 years with moderate to severe AC who received percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: From January 2008 to February 2021, 152 patients were retrospectively enrolled. Clinical outcomes were compared among patients who received laparoscopic cholecystectomy (LC), open cholecystectomy (OC), and conversion surgery, and between those who received early (< 6 weeks after PTGBD) and delayed cholecystectomy (≥ 6 weeks after PTGBD). Logistic regression analysis was used to identify risk factors for recurrent AC, further biliary events, conversion, and perioperative complications. RESULTS: Sixty-seven patients underwent LC, 62 underwent OC, and 23 underwent conversion surgery. Operation-related complications and mortality rates did not differ among the types of surgery; however, LC group had shorter operative time than the other groups. Eighty-two patients underwent early cholecystectomy, while 70 underwent delayed cholecystectomy. There were no differences in operative time, operation-related complications, and mortality rates between the groups. However, higher rates of recurrent AC and biliary events were observed in the delayed cholecystectomy group (52.9% vs. 4.9% and 57.1% vs. 8.5%, p < 0.001). On multivariate analysis, delayed cholecystectomy was a significant risk factor for recurrent AC (odds ratio [OR] = 19.42, p < 0.001) and further biliary events (OR = 15.95, p < 0.001). CONCLUSIONS: Early cholecystectomy is recommended for patients aged ≥ 80 years with moderate to severe AC following PTGBD.

Is China approaching the inflection point of the ecological Kuznets curve? Analysis based on ecosystem service value at the county level.

Accounting for the ecosystem service values (ESVs) and discussing the relationship between the ESVs and economic development can help achieve sustainable ecological development. Therefore, this paper evaluates the county-level ESVs of various land types in China, and depicts the distribution of ESVs in various urban agglomerations. In addition, the nonlinear relationship between ESVs and economic development is revealed. The main findings are as follows: (1) From 2000 to 2018, the ESVs in China decreased, and the decline rate of ESVs in urban agglomerations is much higher than that of China as a whole. (2) The decline rate of ESVs in core cities is much higher than in urban agglomerations, and the decline rate of ESVs is higher in areas close to core cities and lower in areas far from core cities. (3) The ecological Kuznets curve of China has a positive "U" shape, and the ecological Kuznets curve of urban agglomerations has an "N" shape; the ecological Kuznets curve of core cities has a positive "U" shape, while the ESVs of other cities decreases monotonically with the increase of the economic level.

How does digital economy affect carbon emissions? Evidence from global 60 countries.

The digital economy is of great significant for countries to achieve carbon neutrality and carbon peak. Using country-level panel data from 2008 to 2018, this study empirically examined the impact of the development of the digital economy on carbon emissions and the associated transmission mechanisms by using the intermediary effect model. Our main findings are as follows. (1) The level of digital economy development varies greatly between countries, and the difference between "hyper-digitalized countries" and "under-connected countries" is increasingly obvious. (2) Development of the digital economy significantly reduces the carbon emission intensity, but promotes increases in the per capita carbon emissions. (3) Analysis shows that economic growth, financial development, and industrial structure upgrading play mediating roles between the digital economy and carbon emissions. Our study not only advances the study on digital economy and carbon emissions, but also provides a significant reference for policy makers to achieve carbon peak and carbon neutrality.

Transport Infrastructure, High-Quality Development and Industrial Pollution: Fresh Evidence from China.

To achieve high-quality development, transport infrastructure will play a crucial role in China's economic growth, but its damage to the ecological environment has not been paid enough attention. This study was based on panel data for 30 Chinese provinces for the period of 2004-2017. A comprehensive index system for high-quality development based on the new development concept was developed. This high-quality development index used the entropy weight method and integrated transport infrastructure, high-quality development, and industrial pollution into a comprehensive framework, and systematically examined the effects of transport infrastructure and high-quality development on industrial pollution emissions. It was found that transport infrastructure significantly contributed to industrial pollution emissions, and there was a regional heterogeneity and time lag, with high-quality development and industrial pollution having an inverted "U"-shaped relationship. Further analysis showed that transport infrastructure significantly affected high-quality development and industrial pollution through industrial agglomeration, reduced the inhibitory effect on high-quality development by promoting industrial agglomeration, and reduced industrial pollution emissions by promoting industrial agglomeration.

Outcomes of patients with malignant esophagogastric junction obstruction receiving metallic stents: A single-center experience.

BACKGROUND: Malignancies-related esophagogastric junction (EGJ) obstruction is usually diagnosed in inoperable status with poor clinical outcomes. Metallic stent placement at EGJ could improve dysphagia for these patients. However, studies regarding the outcomes in these patients receiving metallic stents are still limited. This study aimed to investigate the outcomes of metallic stent placement in malignant EGJ obstruction. METHODS: Forty-one patients with inoperable malignant EGJ obstruction receiving metallic stent placement were retrospectively enrolled. The clinical outcomes between different stents and deployment techniques were analyzed. RESULTS: The overall technical success rate was 97.6% and clinical success rate was 92.1%. The median overall survival time was 77 (4-893) days, and the patency time was 71 (4-893) days, respectively. Poststent radiotherapy significantly prolonged survival and stent patency. Between patients receiving uncovered or partially covered metal stents, there was no difference in procedure-related complications, survival time, and stent patency time. Moreover, the clinical outcomes in patients receiving duodenal stents for malignant EGJ obstruction are not inferior to those receiving esophageal stents. CONCLUSION: This study provides crucial information for endoscopists to establish individualized stenting strategies for malignant EGJ obstruction.

Towards Carbon Neutrality: The Impact of Renewable Energy Development on Carbon Emission Efficiency.

The energy transition and carbon emission efficiency are important thrust and target functions, respectively, for achieving carbon neutrality in the future. Using a sample of 30 Chinese provinces from 2006 to 2018, we measured their carbon efficiency using the game cross-efficiency data envelopment analysis (DEA). Then, a random forest regression model was used to explore the impact of renewable energy development on regional carbon emission efficiency. The results are as follows. First, China's carbon emission efficiency in the southeast coastal area was better than that in the northwest area. Second, renewable energy development first inhibited and then promoted carbon emission efficiency, and there existed a reasonable range. Third, through a regional heterogeneity analysis, the trend of the influence of renewable energy development on carbon emission efficiency was found to not be significantly different in eastern, central, and western China, but there was a certain gap in the reasonable range. Our study not only helps to promote the study of renewable energy development and the carbon neutral target, but also provides an important reference for Chinese policy-makers to design a reasonable carbon emissions reduction path.

How to optimize provincial PM2.5 reduction targets and paths for emerging industrialized countries? Fresh evidence from China.

Taking China as an example, this paper aims to design a path to reduce haze pollution in newly industrialized countries. Combined the principles of efficiency and equity, this study develops a Game Cross Equity Fixed Cost Allocation Model (Game-EFCAM) to optimize provincial PM2.5 reduction targets and put forward haze reduction paths. The main results are as follows: (1) Among the three egalitarian principles, pay-ability egalitarianism is the fairest, which serves as the convergence principle of Game-EFCAM. (2) The "two mountains and two rivers" area has the largest PM2.5 emission quotas, while the provinces in western China have small PM2.5 emission quotas. In addition, the distributions of PM2.5 emission quotas per unit of population, per unit of gross domestic product, and per unit of area all show significant regional clustering. (3) Shandong and Hebei have the largest amount of PM2.5 emission reduction requirements, while Tianjin and Hainan have the smallest. Xinjiang and Beijing have the largest PM2.5 reduction pressure indexes, while Tianjin and Shanghai have the smallest. This study not only helps China optimize provincial PM2.5 reduction goals, but the proposed allocation method is also applicable to the overall planning of national resources utilization, and provides a reference to newly industrialized countries of haze reduction.

Generation of induced pluripotent stem cells FIRDIi001-A from a Taiwanese subject carrying ALDH2 pE487K mutation.

The ALDH2 mutation (ALDH2*2) is caused by an amino acid substitution ALDH2 rs671 G>A (pE487K) which reduces ALDH2 enzyme activity. When individuals with the ALDH2 mutation consume alcohol, accumulating acetaldehyde in the blood can cause reddened face, headache, nausea, and palpitations; symptoms referred to as Alcohol Flushing Reaction. We report the production of an induced pluripotent stem cell (iPSC) line, FIRDIi001-A, developed from peripheral blood mononuclear cells of a 39-year-old male subject with the ALDH2*2 mutation. The ALDH2-pE487K iPSCs will be valuable in investigating pathogenic mechanisms involved in the link between the ALDH2 polymorphism and alcohol-related diseases.

Economic policy choice of governing haze pollution: evidence from global 74 countries.

Haze pollution not only has a huge impact on economic development but also seriously damages the health of residents, which has attracted the attention of many countries and scholars. The geographical detector model and the panel quantile regression model are used in combination to analyze the socio-economic driving factors of haze pollution from 2010 to 2015 for 74 significantly representative countries. The main results are as follows: (1) Industrial structure is the main factor affecting the haze concentration, followed by economic growth and research and development (R&D) intensity. (2) Government influence and industrial structure will significantly aggravate haze pollution, whereas the energy intensity and economic growth have an inhibitory effect on haze concentration. Countries with severe haze pollution should focus on upgrading their industrial structure and avoiding energy rebound. (3) Urbanization, foreign investment, and R&D intensity have different effects on the haze concentration among countries with different pollution levels. Specifically, the relationship between economic growth and pollution is inverted N-shaped in countries with medium haze concentration, whereas in other countries, it is positive N-shaped. Countries should actively leverage the agglomeration effect of high-density urban populations and focus on the introduction of high-quality foreign capital.

Evolution of Renewable Energy in BRI Countries: A Combined Econometric and Decomposition Approach.

The development of renewable energy is an important cooperation theme among countries along the Belt and Road Initiative (BRI countries). Through map description, we first explore the changes in renewable energy consumption in BRI countries. Then, ß-convergence is employed to examine the development direction of renewable energy consumption in BRI countries. Finally, based on the expanded Kaya equation, we decompose the factors effecting renewable energy consumption into energy structure effect, energy intensity effect, low-carbon economic effect, carbon emission effect, population distribution effect and population effect. The Logarithmic Mean Divisia Index (LMDI) is utilized to calculate the contribution of each factor to renewable energy consumption in the expanded Kaya equation. Our research reaches the following conclusions: (1) ß-convergence exists in renewable energy consumption among BRI countries, indicating that it will converge to a relatively stable level, and countries with low renewable energy consumption will increase their renewable energy consumption with a higher convergence rate to chase the countries with high renewable energy consumption. (2) Energy structure effect makes a positive impact on renewable energy consumption, and is the main contributor to renewable energy consumption. (3) The energy intensity effect makes a negative contribution to renewable energy consumption, and the negative impact has deepened in recent years. (4) Both the low-carbon economic effect and the carbon emission effect have positive impacts on renewable energy consumption. Our research not only provides a description of the experience of developing renewable energy for BRI countries, but also makes reference to other organizations.

How to Evaluate Provincial Ecological Civilization Construction? The Case of Jiangsu Province, China.

Ecological civilization is a transcendence of industrial civilization. The improvement of China's ecological civilization system can not only provide developing countries with an empirical reference for ecological civilization construction, but also make a huge contribution to the progress of global ecological civilization. This paper focuses on improving the provincial ecological civilization evaluation system. First, the Provincial Ecological Civilization Construction Evaluation Index System is established according to the Green Development Index System issued by the Chinese government in 2016, and then the applicability of the Spatio-Temporal Factor Analysis (STFA) is verified as the evaluation method of the provincial ecological civilization construction level. Further, taking Jiangsu Province, China as an example, this paper evaluates the level of ecological civilization construction in each city of Jiangsu Province, and analyzes the main factors affecting ecological civilization based on the evaluation results. Finally, according to the relationship between the ecological civilization construction and economic quality of each city, the four-quadrant method is applied to divide Jiangsu Province into four types of regions to help each city position itself in ecological civilization construction. This paper mainly draws the following conclusions: (1) Due to its simple operation and accurate evaluation results, STFA is applicable in evaluating the provincial ecological civilization construction level. (2) Taking Jiangsu Province as an example, it is found that the level of ecological civilization construction in the southwestern region is higher than that of the northeast coastal region in Jiangsu. Three inequality indices are applied to measure the regional inequality of ecological civilization construction among 13 cities, which is relatively high in recent years. (3) By analyzing the results of STFA, it is found that economic quality and natural protection are not only the main factors affecting the ecological civilization construction in Jiangsu province, but also the main reasons for the regional heterogeneity of provincial ecological civilization. (4) For the four types of regions, suggestions are proposed according to the characteristics of each region to help improve the provincial ecological civilization construction level. This paper not only improves China's ecological civilization construction system, but also provides information for the provincial ecological civilization construction in developing countries.