Mining co-location patterns of manufacturing firms using Q statistic and additive color mixing.

The agglomeration effect significantly influences firms' site selection. Manufacturing firms often exhibit intricate spatial co-location patterns that are indicative of agglomerations due to their reliance on material input and product output across various subdivisions of manufacture. In this study, we present an analytical approach employing the Q statistic and additive color mixing visualization to assess co-location patterns of manufacturing firms. We identified frequent pairs and triplets of manufacturing divisions, mapping them to reveal distinct categories: labor-intensive clusters, upstream/downstream industrial chains, and technology-spillover clusters. These agglomeration categories concentrate in different regions of the city. Policy implications are proposed to promote the upgrade of labor-intensive divisions, enhance the operational efficiency of upstream/downstream industrial chains, and reinforce the spillover effects of technology-intensive divisions.

Small Extracellular Vesicles Derived from Altered Peptide Ligand-Loaded Dendritic Cell Act as A Therapeutic Vaccine for Spinal Cord Injury Through Eliciting CD4+ T cell-Mediated Neuroprotective Immunity.

The balance among different CD4+ T cell subsets is crucial for repairing the injured spinal cord. Dendritic cell (DC)-derived small extracellular vesicles (DsEVs) effectively activate T-cell immunity. Altered peptide ligands (APLs), derived from myelin basic protein (MBP), have been shown to affect CD4+ T cell subsets and reduce neuroinflammation levels. However, the application of APLs is challenging because of their poor stability and associated side effects. Herein, it is demonstrate that DsEVs can act as carriers for APL MBP87-99 A91 (A91-DsEVs) to induce the activation of 2 helper T (Th2) and regulatory T (Treg) cells for spinal cord injury (SCI) in mice. These stimulated CD4+ T cells can efficiently "home" to the lesion area and establish a beneficial microenvironment through inducing the activation of M2 macrophages/microglia, inhibiting the expression of inflammatory cytokines, and increasing the release of neurotrophic factors. The microenvironment mediated by A91-DsEVs may enhance axon regrowth, protect neurons, and promote remyelination, which may support the recovery of motor function in the SCI model mice. In conclusion, using A91-DsEVs as a therapeutic vaccine may help induce neuroprotective immunity in the treatment of SCI.

Recent design strategies and applications of organic fluorescent probes for food freshness detection.

Food spoilage poses a significant risk to human health, making the assessment of food freshness essential for ensuring food safety and quality. In recent years, there has been rapid progress in the development of fast detection technologies for food freshness. Among them, organic fluorescent probes have garnered significant attention in the field of food safety and sensing due to their easy functionalization, high sensitivity, and user-friendly nature. To comprehensively examine the latest advancements in organic fluorescent probes for food freshness detection, this review summarized their applications within the past five years. Initially, the fundamental detection principles of organic fluorescent probes are outlined. Subsequently, the recent research progress in utilizing organic fluorescent probes to detect various chemical indicators of freshness are discussed. Finally, the challenges and future directions for organic fluorescent probes in food freshness detection are elaborated upon. While, organic fluorescent probes have demonstrated their effectiveness in evaluating food freshness and possess great potential for practical applications, further research is still needed to enable their widespread commercial utilization. With continued advancements in synthesis and functionalization techniques, organic fluorescent probes will contribute to enhancing the efficiency of food safety detection.

Portable visual and electrochemical detection of hydrogen peroxide release from living cells based on dual-functional Pt-Ni hydrogels.

It is important to monitor the intra-/extracellular concentration of hydrogen peroxide (H2O2) in biological processes. However, miniaturized devices that enable portable and accurate H2O2 measurement are still in their infancy because of the difficulty of developing facile sensing strategies and highly integrated sensing devices. In this work, portable H2O2 sensors based on Pt-Ni hydrogels with excellent peroxidase-like and electrocatalytic activities are demonstrated. Thus, simple and sensitive H2O2 sensing is achieved through both colorimetric and electrochemical strategies. The as-fabricated H2O2 sensing chips exhibit favorable performance, with low detection limits (0.030 µM & 0.15 µM), wide linearity ranges (0.10 µM-10.0 mM & 0.50 µM-5.0 mM), outstanding long-term stability (up to 60 days), and excellent selectivity. With the aid of an M5stack development board, portable visual and electrochemical H2O2 sensors are successfully constructed without complicated and expensive equipment or professional operators. When applied to the detection of H2O2 released from HeLa cells, the results obtained by the developed sensors are in good agreement with those from an ultraviolet‒visible spectrophotometer (UV‒vis) (1.97 µM vs. 2.08 µM) and electrochemical station (1.77 µM vs. 1.84 µM).

Quantitative analysis method of Panax notoginseng based on thermal perturbation terahertz two-dimensional correlation spectroscopy.

This paper proposes a Panax notoginseng (P. notoginseng) quantitative analysis based on terahertz time-domain spectroscopy and two-dimensional correlation spectroscopy (2DCOS). By imposing temperature perturbation combined with 2DCOS, the one-dimensional absorbance spectra were transformed into 2DCOS synchronous spectra, which reflected the differences in characteristic information between different P. notoginseng contents more clearly. Then, the feature information of P. notoginseng contents was extracted from the 2DCOS synchronous spectra by a competitive adaptive reweighted sampling (CARS) method and was used to build a quantitative model combined with a support vector regression machine (SVR), called 2DCOS-CARS-SVR. We obtained a more accurate analysis result than the commonly used principal component analysis (PCA)-partial least squares regression (PLSR) and PCA-SVR. The prediction set correlation coefficient and root mean square error reached 0.9915% and 0.8160%, respectively.

Single-cell analysis of spinal cord injury reveals functional heterogeneity of oligodendrocyte lineage cells.

Spinal cord injury (SCI) is a traumatic condition that causes myelin destruction and neuronal death, making it challenging to reverse. In spinal cord tissue, oligodendrocyte progenitor cells and oligodendrocytes are essential for maintaining myelin morphology and axon regeneration. The decrease in oligodendrocyte lineage cells after SCI is a major factor contributing to the difficulty in restoring spinal cord function. However, there is still a lack of research on the status and intercellular communication between oligodendrocyte lineage cells after injury. The development of single-cell sequencing technology has enabled researchers to obtain highly accurate cellular transcriptional information, facilitating detailed studies of cellular subpopulations. This study delved into the cellular heterogeneity of oligodendrocyte lineage cells using a single-cell transcriptomic approach to uncover functional changes and cellular interactions during different time points after SCI. Our findings highlighted the critical roles of Psap (Prosaposin)/Gpr37l1 and Psap/Gpr37 ligand-receptor pairs among oligodendrocyte lineage cells. Furthermore, we predicted the transcription factors that may play a key regulatory role. We demonstrated for the first time that Junb acts almost exclusively in mature oligodendrocytes, which provides a potential target for the study of oligodendrocyte transcriptional mechanisms.

Effect of Heat-Moisture Treatment on the Structure and Digestibility of Sweet Potato Starch.

The objective of this study was to investigate the effect of temperature changes during heat-moisture treatment (HMT) on the appearance, structure and digestibility of sweet potato starch (SPS). The results showed that after HMT, there were depressions, cavities and fragments on the surface of SPS particles. The polarized crosses of SPS were irregular and partially blurred. The relative crystallinity and short-range order of SPS decreased, while rearrangement and reorientation of the starch molecules occurred and the thermal stability increased. The resistant starch content of SPS reached the highest (24.77%) after 4 h treatment at 110 °C and 25% moisture. The obtained results can provide a reference for the modification of SPS.

Effects of sodium carboxymethyl cellulose on storage stability and qualities of different frozen dough.

Hydrocolloids as Additives have been used for improving the quality of frozen dough for a long time. In this work, the effects of sodium carboxymethyl cellulose (CMC) on quality changes of frozen dough in storage were studied. The water loss rate of the dough and water holding capacity were measured. Rheological and texture properties of the frozen dough were measured by a rheometer and a texture analyzer, respectively. Scanning electron microscopy (SEM) was used to characterize surface network structure and protein structure changes of the frozen dough. Our results reveal that the addition of CMC can inhibit the formation of ice crystals and recrystallization, thus effectively stabilizing the molecular structure of starch, and resulting in more uniform moisture distribution in the frozen dough. When 3% addition of CMC, the water holding capacity of the two kinds of dough reached the best, and the water loss rate of corn dough reached the lowest. The cohesion of the two kinds of dough reaches the maximum with 3 wt% addition of CMC, while the hardness and chewiness of wheat and corn multigrain dough reaches the maximum with 3 wt% and 4 wt% addition of CMC, respectively. The results show proper CMC addition (3 wt% and 4 wt%) finally improves the stability and qualities of the frozen dough. The research concerning the effects of CMC on quality of frozen dough provides better understanding for the frozen food industry.

Arsenic Contents, Speciation and Toxicity in Germinated Rice Alleviated by Selenium.

Rice can accumulate more organic and inorganic arsenic (iAs) than other crop plants. In this study, the localization of As in rice grains was investigated using High Performance Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry (HPLC-ICP-MS) based on 26 rice varieties collected from two provinces. In all the samples, the total As contents in polished rice were 0.03-0.37 mg/kg, with average values of 0.28 and 0.21 mg/kg for two sample sets. The results of the determination of arsenic speciation in different components of rice grain showed that in the polished and brown rice the mean value of arsenite (As(III)) was nearly twice than that of arsenate (As(V)). The regional difference was observed in both total As contents and As speciation. The reason may be that As(III) is more mobile than As(V) in a dissociated form and because of soil properties, rice varieties, and the growing environment. The proportion of iAs and the total As in rice bran was higher than that in polished rice, and this is because As tends accumulate between the husk and the endosperm. In our study, selenium could alleviate the risk of arsenic toxicity at the primary stage of rice growth. Co-exposure to As and Se in germinated rice indicated that the reduction in As accumulation in polished rice reached 73.8%, 76.8%, and 78.3% for total As, As(III), and As(V) when compared with rice treated with As alone. The addition of Se (0.3 mg/kg) along with As significantly reduced the As amount in different parts of germinated rice. Our results indicated that Se biofortification could alleviate the As accumulation and toxicity in rice crops.

PE-STOP: A versatile tool for installing nonsense substitutions amenable for precise reversion.

The rapid advances in genome editing technologies have revolutionized the study of gene functions in cell or animal models. The recent generation of double-stranded DNA cleavage-independent base editors has been suitably adapted for interrogation of protein-coding genes on the basis of introducing premature stop codons or disabling the start codons. However, such versions of stop/start codon-oriented genetic tools still present limitations on their versatility, base-level precision, and target specificity. Here, we exploit a newly developed prime editor (PE) that differs from base editors by its adoption of a reverse transcriptase activity, which enables incorporation of various types of precise edits templated by a specialized prime editing guide RNA. Based on such a versatile platform, we established a prime editing-empowered method (PE-STOP) for installation of nonsense substitutions, providing a complementary approach to the present gene-targeting tools. PE-STOP is bioinformatically predicted to feature substantially expanded coverage in the genome space. In practice, PE-STOP introduces stop codons with good efficiencies in human embryonic kidney 293T and N2a cells (with medians of 29% [ten sites] and 25% [four sites] editing efficiencies, respectively), while exhibiting minimal off-target effects and high on-target precision. Furthermore, given the fact that PE installs prime editing guide RNA-templated mutations, we introduce a unique strategy for precise genetic rescue of PE-STOP-dependent nonsense mutation via the same PE platform. Altogether, the present work demonstrates a versatile and specific tool for gene inactivation and for functional interrogation of nonsense mutations.

Development and application of lateral flow strip with three test lines for detection of deoxynivalenol in wheat.

Lateral flow strip was widely used and their qualitative and quantitative performance was in continuous improvement. However, the traditional strip was in a single-test-line format, which restricted operators to making a semi-quantitative judgment around a desired threshold concentration. Herein, a single strip with three test lines (TTLS) was developed for the semi-quantitative and quantitative determination of deoxynivalenol (DON). Four visual detection thresholds were obtained under optimized conditions and 35 wheat samples with DON content from 45 µg/kg to 2841 µg/kg were used to verify the method. The detection results were compared with that of the traditional strip and UPLC-MS/MS. In a three-test-line format, TTLS could reveal at least 200, 500, 1000, and 2000 µg/kg DON existed in different samples by the naked eye. The agreement analysis and statistical results indicated the new TTLS can be used as a useful tool for quantitative detection of DON with wide dynamic range.

Advances in CRISPR/Cas gene therapy for inborn errors of immunity.

Inborn errors of immunity (IEIs) are a group of inherited disorders caused by mutations in the protein-coding genes involved in innate and/or adaptive immunity. Hematopoietic stem cell transplantation (HSCT) is a mainstay definitive therapy for many severe IEIs. However, the lack of HLA-matched donors increases the risk of developing severe immunological complications. Gene therapy provides long-term clinical benefits and could be an attractive therapeutic strategy for IEIs. In this review, we describe the development and evolution of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated proteins (Cas) gene-editing systems, including double-strand break (DSB)-based gene editing and DSB-free base editing or prime editing systems. Here, we discuss the advances in and issues associated with CRISPR/Cas gene editing tools and their potential as therapeutic alternatives for IEIs. We also highlight the progress of preclinical studies for the treatment of human genetic diseases, including IEIs, using CRISR/Cas and ongoing clinical trials based on this versatile technology.

Nonenzymatic Sweat Wearable Uric Acid Sensor Based on N-Doped Reduced Graphene Oxide/Au Dual Aerogels.

Sweat wearable sensors enable noninvasive and real-time metabolite monitoring in human health management but lack accuracy and wearable applicability. The rational design of sensing electrode materials will be critical yet challenging. Herein, we report a dual aerogel-based nonenzymatic wearable sensor for the sensitive and selective detection of uric acid (UA) in human sweat. The three-dimensional porous dual-structural aerogels composed of Au nanowires and N-doped graphene nanosheets (noted as N-rGO/Au DAs) provide a large active surface, abundant access to the target, rapid electron transfer pathways, and a high intrinsic activity. Thus, a direct UA electro-oxidation is demonstrated at the N-rGO/Au DAs with a much higher activity than those at the individual gels (i.e., Au and N-rGO). Moreover, the resulting sensing chip displays high performance with a good anti-interfering ability, long-term stability, and excellent flexibility toward the UA detection. With the assistance of a wireless circuit, a wearable sensor is successfully applied in the real-time UA monitoring on human skin. The obtained result is comparable to that evaluated by high-performance liquid chromatography. This dual aerogel-based nonenzymatic biosensing platform not only holds considerable promise for the reliable sweat metabolite monitoring but also opens an avenue for metal-based aerogels as flexible electrodes in wearable sensing.

Cross-sectional study and bioinformatics analysis to reveal the correlations of osteoporosis in patients with Parkinson's disease.

OBJECTIVES: Osteoporosis and Parkinson's disease (PD) are both aging-related diseases. PD patients with comorbid osteoporosis are vulnerable to the risk of fracture, which leads to a serious public health burden to the whole society. Therefore, this study sought to reveal the clinical and genetic correlations between PD and osteoporosis based on a cross-sectional study and bioinformatics analysis. METHODS: A cross-sectional study of 95 PD patients and 99 healthy controls was conducted. Ordinal logistic regression analysis was utilized to investigate the clinical correlations between PD and osteoporosis. Two microarray datasets (GSE20292, GSE35958) including PD, osteoporosis and normal control samples were retrieved from the GEO database for GO analysis, KEGG pathway analysis and PPI network. RESULTS: PD patients had lower 25(OH)VitD, FN BMD, BMD and T-score of the LS and TH, as well as poorer bone mass diagnosis, yet higher PINP compared to healthy controls. Both age and UPDRS II score of PD patients were adversely correlated with BMD of LS and TH. PD diagnosis acted as an independent risk factor of osteoporosis, and PD patients had approximately double risk for osteoporosis. Bioinformatics analysis further revealed that SNAP25, AQP4, SV2B, KCND3, and ABCA2 had important diagnostic value and risk prediction value for both PD and osteoporosis. CONCLUSIONS: PD diagnosis can be used as an independent risk factor for osteoporosis. Moreover, SNAP25, AQP4, SV2B, KCND3 and ABCA2 as the top 5 hub genes have important diagnostic and risk predictive value for both PD and osteoporosis.

Dual Structural Design of Platinum-Nickel Hydrogels for Wearable Glucose Biosensing with Ultrahigh Stability.

Wearable glucose sensors are of great significance and highly required in mobile health monitoring and management but suffering from limited long-term stability and wearable adaptability. Here a simultaneous component and structure engineering strategy is presented, which involves Pt with abundant Ni to achieve three-dimensional, dual-structural Pt-Ni hydrogels with interconnected networks of PtNi nanowires and Ni(OH)2 nanosheets, showing prominent electrocatalytic activity and stability in glucose oxidation under neutral condition. Specifically, the PtNi(1:3) dual hydrogels shows 2.0 and 270.6 times' activity in the glucose electro-oxidation as much as the pure Pt and Ni hydrogels. Thanks to the high activity, structural stability, good flexibility, and self-healing property, the PtNi(1:3) dual gel-based non-enzymatic glucose sensing chip is endowed with high performance. It features a high sensitivity, an excellent selectivity and flexibility, and particularly an outstanding long-term stability over 2 months. Together with a pH sensor and a wireless circuit, an accurate, real-time, and remote monitoring of sweat glucose is achieved. This facile design of novel dual-structural metallic hydrogels sheds light to rationally develop new functional materials for high-performance wearable biosensors.

Systematic analysis of microbiota in pregnant Chinese women and its association with miscarriage.

Background: Miscarriage is the most common adverse pregnancy outcome and more than 50% of its incidence remains unexplained. Earlier studies have suggested that maternal microbiota might be associated with miscarriage, but the association is insufficiently understood. Methods: We used 16S ribosomal RNA (rRNA) amplicon sequencing and metagenomic sequencing technology to characterize the bacterial composition of three sites including the rectum, vagina, and cervix of a case group of 63 pregnant women who had miscarried compared to a control group of 24 pregnant women who underwent voluntary elective abortion. Results: The alpha-diversity from the rectum and cervix was significantly decreased in the case group relative to the control group. However, we did not find significant differences in microbial diversity of vaginal samples between the two groups. Lactobacillus was the most predominant genus in the cervix and vaginal samples. Gestational age at the time of surgery was positively associated with the rectum microbiota diversity, with an effect size of 10% (P=0.004). Host factors including gestational age and red blood count (RBC) were associated with the rectal microbiota diversity. Conclusions: We detected a significantly lower rectal microbiota diversity and a pro-inflammatory tendency in the miscarriage group. This is the first study to investigate the association of microbiota from samples collected from three sites and miscarriage. Further studies are warranted to explore further the role of microbiota in miscarriage.

De novo assisted AFB1-Specific monoclonal antibody sequence assembly and comprehensive molecular characterization.

Despite their widely used and access as biological reagents in analytical methods, the detailed structural features for most of the antibodies were rarely known. Here, a new antibody for AFB1 with high specificity in constructing ELISA was studied in detail. The molecular structure and modification were elucidated mainly by nano-electrospray ionization mass spectrometry. The mass experiments, including MALDI-TOF MS, revealed complete and specific fragments, including antibody molecular weight, peptides, glycopeptide, and N-glycoform. By proteolytic treatment of pepsin and trypsin and high-resolution tandem-MS, the primary structure of the newly developed anti-AFB1 antibody was assembled by several rounds of Database search process assisted with the de novo results. The antibody CDR annotation and constraint-based multiple alignment tool were used to differentiate and align the sequences. The method uses only two proteases to generate numerous peptides for de novo sequencing. This artificial assembled AFB1-specific monoclonal antibody sequence was validated by comparison with the sequencing results of the immunoglobulin gene. The results showed that this method achieves full sequence coverage of anti-AFB1 monoclonal antibody, with an accuracy of 100% in the CDR regions of light chain and four amino acid mismatch in heavy chain. This simple and low-cost method was confirmed by treating a public dataset. The secondary structure information of intact antibody was also elucidated from the results of circular dichroism spectrum.

Effects of supplementation with lysophospholipids on performance, nutrient digestibility, and bacterial communities of beef cattle.

An experiment was conducted to investigate the influences of supplemental lysophospholipids (LPL) on the growth performance, nutrient digestibility, and fecal bacterial profile, and short-chain fatty acids (SCFAs) of beef cattle. Thirty-six Angus beef cattle [565 ± 10.25 kg body weight (BW)] were grouped by BW and age, and randomly allocated to 1 of 3 treatment groups: (1) control (CON, basal diet); (2) LLPL [CON supplemented with 0.5 g/kg LPL, dry matter (DM) basis]; and (3) HLPL (CON supplemented with 0.75 g/kg, DM basis). The Angus cattle were fed a total mixed ration that consisted of 25% roughage and 75% concentrate (dry matter [DM] basis). The results reveal that LPL inclusion linearly increased the average daily gain (P = 0.02) and the feed efficiency (ADG/feed intake, P = 0.02), while quadratically increasing the final weight (P = 0.02) of the beef cattle. Compared with CON, the total tract digestibilities of DM (P < 0.01), ether extract (P = 0.04) and crude protein (P < 0.01) were increased with LPL supplementation. At the phylum-level, the relative abundance of Firmicutes (P = 0.05) and ratio of Firmicutes: Bacteroidetes (P = 0.04) were linearly increased, while the relative abundances of Bacteroidetes (P = 0.04) and Proteobacteria (P < 0.01) were linearly decreased with increasing LPL inclusion. At the genus-level, the relative abundances of Clostridium (P < 0.01) and Roseburia (P < 0.01) were quadratically increased, and the relative abundances of Ruminococcus was linearly increased (P < 0.01) with LPL supplementation. Additionally, increasing the dose of LPL in diets linearly increased the molar proportion of butyrate (P < 0.01) and total SCFAs (P = 0.01) concentrations. A conclusion was drawn that, as a promising feed additive, LPL promoted growth performance and nutrient digestibility, which may be associated with the change of fecal microbiome and SCFAs.