Application status and optimization suggestions of tumor organoids and CAR-T cell co-culture models.

Tumor organoids, especially patient-derived organoids (PDOs) exhibit marked similarities in histopathological morphology, genomic alterations, and specific marker expression profiles to those of primary tumour tissues. They are applied in various fields including drug screening, gene editing, and identification of oncogenes. However, CAR-T therapy in the treatment of solid tumours is still at an exploratory stage. Tumour organoids offer unique advantages over other preclinical models commonly used for CAR-T therapy research, which the preservation of the biological characteristics of primary tumour tissue is critical for the study of early-stage solid tumour CAR-T therapies. Although some investigators have used this co-culture model to validate newly targeted CAR-T cells, optimise existing CAR-T cells and explore combination therapy strategies, there is still untapped potential in the co-culture models used today. This review introduces the current status of the application of tumour organoid and CAR-T cell co-culture models in recent years and commented on the limitations of the current co-cultivation model. Meanwhile, we compared the tumour organoid model with two pre-clinical models commonly used in CAR-T therapy research. Eventually, combined with the new progress of organoid technologies, optimization suggestions were proposed for the co-culture model from five perspectives: preserving or reconstructing the tumor microenvironment, systematization, vascularization, standardized culture procedures, and expanding the tumor organoids resource library, aimed at assisting related researchers to better utilize co-culture models.

Sleep quality and psychological health in patients with pelvic and acetabulum fractures: a cross-sectional study.

BACKGROUND AND OBJECTIVES: It is known that difficulty sleeping after a fracture can have negative effects on both mental and physical health and may prolong the recovery process. The objective of this study is to explore how sleep quality and psychological health are linked in patients with pelvic and acetabulum fractures. METHODS: A study was conducted on 265 patients between 2018 and 2022 who had suffered pelvic and acetabulum fractures. The study examined various factors, including age, gender, cause of injury, post-operative complications, and injury severity. The study employed ordinal logistic regression to examine the relationship between various pelvic fractures and seven subscales of the Majeed Pelvic Score (MPS), as well as the Sleep Disorder Questionnaire (SDQ) and Beck Depression Inventory (BDI). The study focused on the postoperative outcome one year after surgery, and each patient was assessed at the one-year mark after surgical intervention. Additionally, the study evaluated the functional outcome, sleep quality, and psychological disorders of the patients. RESULTS: From 2018 to 2022, a total of 216 patients suffered from pelvic and acetabulum fractures. Among them, 6.6% experienced borderline clinical depression, and 45.2% reported mild mood disturbances. Anxiety was found to be mild to moderate in 46% of Tile C and posterior acetabulum wall fracture patients. About 24.8% of patients reported insomnia, while 23.1% reported sleep movement disorders. However, no significant correlation was found between fracture types and sleep disorders. The mean Majeed pelvic score (MPS) was 89.68. CONCLUSIONS: Patients with pelvic and acetabular fractures typically experience functional improvement, but may also be at increased risk for insomnia and sleep movement disorders, particularly for certain types of fractures. Psychological well-being varies between fracture groups, with signs of borderline clinical depression observed in some cases. However, anxiety levels do not appear to be significantly correlated with pelvic and acetabular fractures.

Generation and characterization of intense terahertz pulses from DSTMS crystal.

Matter manipulation in terahertz range calls for a strong-field broadband light source. Here, we present a scheme for intense terahertz generation from DSTMS crystal driven by a high power optical parametric chirped pulse amplifier. The generated terahertz energy is up to 175 µJ with a peak electric field of 17 MV/cm. The relationship between terahertz energy, conversion efficiency, and pump fluence is demonstrated. This study provides a powerful driving light source for strong-field terahertz pump-probe experimentation.

Ultrafast and ultrastable FeSe2embedded in nitrogen-doped carbon nanofibers anode for sodium-ion half/full batteries.

Transition metal selenides are considered as promising anode materials for fast-charging sodium-ion batteries due to their high theoretical specific capacity. However, the low intrinsic conductivity, particle aggregation, and large volume expansion problems can severely inhibit the high-rate and long-cycle performance of the electrode. Herein, FeSe2nanoparticles embedded in nitrogen-doped carbon nanofibers (FeSe2@NCF) have been synthesized using the electrospinning and selenization process, which can alleviate the volume expansion and particle aggregation during the sodiation/desodiation and improve the electrical conductivity of the electrode. The FeSe2@NCF electrode delivers the outstanding specific capacity of 222.3 mAh g-1at a fast current density of 50 A g-1and 262.1 mAh g-1at 10 A g-1with the 87.8% capacity retention after 5000 cycles. Furthermore, the Na-ion full cells assembled with pre-sodiated FeSe2@NCF as anode and Na3V2(PO4)3/C as cathode exhibit the reversible specific capacity of 117.6 mAh g-1at 5 A g-1with the 84.3% capacity retention after 1000 cycles. This work provides a promising way for the conversion-based metal selenides for the applications as fast-charging sodium-ion battery anode.

Bacterial distinctions in practical rural sewage collection systems caused by the location, season, and system type.

Bacteria in rural sewage collection systems have the important influences on operation and maintenance risks, such as sedimentation blockage and harmful gas accumulation, and pollutant pre-treatment ability. It is necessary to analyze and interpret the influence on bacterial communities caused by the location (sewage, biofilms, and deposits), season (winter and spring, summer and autumn), and system type (sewers and ditches) to better understand the bacterial characteristics in rural sewage collection systems. To achieve the above purpose, 96 samples obtained from practical rural sewage collection systems in eight villages were analyzed by 16S rRNA whole region sequencing methods. The results indicate that locations and seasons caused significant influences on the overall bacterial communities, which were mainly affected by temperature, sewage quality and bacterial survival preference, and 13 genera of sulfate-reducing bacteria (SRB), 2 genera of ammonia-oxidizing bacteria (AOB), 2 genera of nitrite-oxidizing bacteria (NOB), and 9 genera of water-related pathogenic bacteria (WPB) were detected in rural sewage collection systems. SRB, AOB, NOB, and WPB tended to inhabit in biofilms or deposits rather than in sewage. The total relative abundance of SRB in summer and autumn (∼2.19%) was higher than in winter and spring (∼0.41%), and the WPB distribution in different seasons showed significant distinction. Additionally, some of SRB, AOB, NOB, and WPB also showed significant differences in sewers and ditches. Overall, this study provided a deeper understanding of bacteria in rural sewage collection systems and could further provide the basic parameter for the operation and maintenance risk control.

Network-based methods for predicting essential genes or proteins: a survey.

Genes that are thought to be critical for the survival of organisms or cells are called essential genes. The prediction of essential genes and their products (essential proteins) is of great value in exploring the mechanism of complex diseases, the study of the minimal required genome for living cells and the development of new drug targets. As laboratory methods are often complicated, costly and time-consuming, a great many of computational methods have been proposed to identify essential genes/proteins from the perspective of the network level with the in-depth understanding of network biology and the rapid development of biotechnologies. Through analyzing the topological characteristics of essential genes/proteins in protein-protein interaction networks (PINs), integrating biological information and considering the dynamic features of PINs, network-based methods have been proved to be effective in the identification of essential genes/proteins. In this paper, we survey the advanced methods for network-based prediction of essential genes/proteins and present the challenges and directions for future research.

Linkage disequilibrium under polysomic inheritance.

Linkage disequilibrium (LD) is the non-random association of alleles at different loci. Squared LD coefficients r2 (for phased genotypes) and [Formula: see text] (for unphased genotypes) will converge to constants that are determined by the sample size, the recombination frequency, the effective population size and the mating system. LD can therefore be used for gene mapping and the estimation of effective population size. However, current methods work only with diploids. To resolve this problem, we here extend the linkage disequilibrium measures to include polysomic inheritance. We derive the values of r2 and [Formula: see text] at equilibrium state for various mating systems and different ploidy levels. For unlinked loci, [Formula: see text] for monoecious and dioecious (with random pairing) mating systems or [Formula: see text] for dioecious mating systems (with lifetime pairing), where f is the number of females in a half-sib family and η is a constant related to the ploidy level. We simulate the application of estimating Ne using unphased genotypes. We find that estimating Ne in polyploids requires similar sample sizes and numbers of loci as in diploids, with the main source of bias due to using 0.5 as the recombination frequency.

The difference between drainage channels and sewers in rural areas: from sewage quality to bacterial characteristics.

Channels and sewers are commonly used to collect sewage during extensively rural areas. The sewage and bacterial characteristics of rural sewage collection systems can influence their operation and maintenance performance which further affect appropriate system decision. In this study, eight rural sewage collection systems (four each of channels and sewers) were applied to evaluate the sewage quality, bacterial characteristics, and their differences of two kinds of collection systems. The results indicate that significantly distinction existed between the rural sewage collection systems of channels and sewers. Sewage in channels had higher suspended solid (SS) concentration but lower sulfide concentration than that in sewers. The SS, sulfate, and chemical oxygen demand (COD) removal capacity in channels was nearly 3.5, 4.0, and 0.6 times than those in sewers. At least 14 genera and 18 species of bacteria showed significantly distinction between channels and sewers even their main phylum, genus, and species of bacteria communities was Proteobacteria (∼70.3%), Acinetobacter (∼22.3%), and Pseudomonas fragi (∼13.8%), respectively. The structural characteristics and bacterial function caused the difference between channels and sewers. Overall, this study revealed the intrinsic and essential differences of channels and sewers, providing basic and meaningful data for rural sewage collection systems decision.

miRNA-34b/c regulates mucus secretion in RSV-infected airway epithelial cells by targeting FGFR1.

Respiratory syncytial virus (RSV) infection in airway epithelial cells is the main cause of bronchiolitis in children. Excessive mucus secretion is one of the primary symbols in RSV related lower respiratory tract infections (RSV-related LRTI). However, the pathological processes of mucus hypersecretion in RSV-infected airway epithelial cells remains unclear. The current study explores the involvement of miR-34b/miR-34c in mucus hypersecretion in RSV-infected airway epithelial cells by targeting FGFR1. First, miR-34b/miR-34c and FGFR1 mRNA were quantified by qPCR in throat swab samples and cell lines, respectively. Then, the luciferase reporters' assay was designed to verify the direct binding between FGFR1 and miR-34b/miR-34c. Finally, the involvement of AP-1 signalling was assessed by western blot. This study identified that miR-34b/miR-34c was involved in c-Jun-regulated MUC5AC production by targeting FGFR1 in RSV-infected airway epithelial cells. These results provide some useful insights into the molecular mechanisms of mucus hypersecretion which may also bring new potential strategies to improve mucus hypersecretion in RSV disease.

Few-cycle mid-infrared laser based on nonlinear self-compression in solid thin plates.

A few-cycle mid-infrared (MIR) laser is demonstrated via nonlinear self-compression in solid thin plates. In this novel solution, the anomalous material dispersion in the MIR band and the chirp induced by self-phase modulation are mutually compensated, which can achieve self-compression. Finally, with the 4 µm laser injection with 4.8 mJ/155 fs and few-cycle pulses with 3.44 mJ, 29.4 fs are generated with a high efficiency of 71.7%, and the system maintains very good spectral stability in 10 days. Compared with other post-compression methods, this self-compression technique has the advantages of high efficiency and robust and large energy expansion scale, which can be further extended to MIR lasers with other wavelengths and higher peak power.

Analysis of suitable private-secondary-main sewer diameters in rural areas based on cost model and hydraulic calculation.

High cost of sewer systems usually restricts the sewage collection in rural areas. Many rural areas take traditional sewer scheme whose private-secondary-main sewer diameter is 110-200-300 mm without hydraulic calculation and increased the total cost of sewers. The rational utilization of small diameter sewers might contribute to sewer cost reduction. In this study, rural sewer length and cost models were established taking sewer diameter, household number, and length/width ratio of village as parameters to evaluate the cost benefits of using small diameter sewers. Hydraulic calculation of sewers was applied by Storm Water Management Model to ensure the small diameter sewers were feasible. The results indicate that household number and length/width ratio cause obvious impact on sewer length and cost. Main sewer with 200 mm diameter is suitable for the village with less than 1000 households. Using small diameter sewers can reduce the sewer cost by 6-15% compared with traditional sewer scheme and 110-110-200 might be the better scheme to rural areas because of the low cost (including construction cost and operation and maintenance cost) and high tolerance of sewage flow fluctuation. This study provided the suitable diameter of rural sewers based on cost model and hydraulic calculation which might be helpful for the application of rural sewers.

Hepatocellular HO-1 mediated iNOS-induced hepatoprotection against liver ischemia reperfusion injury.

Hepatocyte-derived inducible nitric oxide synthase (iNOS) was proved to impart protection against liver ischemia reperfusion (I/R) injury in our prior analysis. However, the mechanism for this hepatoprotection remains incompletely understood. Bone marrow chimeric mice were generated using expression of iNOS in a hepatocyte-selective manner against an iNOS-knockout background. The function of heme oxygenase 1 (HO-1) in iNOS-stimulated hepatoprotection and the molecular mechanisms were explored in vitro and in vivo, respectively. Hepatocyte-derived iNOS conferred protection from I/R injury and anoxia/reoxygenation stimulation. Mechanistically, iNOS activated nuclear factor erythroid 2-related factor 2 (Nrf-2) and subsequently, stimulated the transcription of HO-1. Results from our study led to the conclusion that HO-1 is another potent mediator of iNOS-mediated protection after liver I/R.

Long-wavelength-infrared laser filamentation in solids in the near-single-cycle regime.

We experimentally demonstrate long-wavelength-infrared (LWIR) femtosecond filamentation in solids. Systematic investigations of supercontinuum (SC) generation and self-compression of the LWIR pulses assisted by laser filamentation are performed in bulk KrS-5 and ZnSe, pumped by ${\sim}{145}\;{\rm fs}$∼145fs, 9 µm, 10 µJ pulses from an optical parametric chirped-pulse amplifier operating at 10 kHz of repetition rate. Multi-octave SC spectra are demonstrated in both materials. While forming stable single filament, 1.5 cycle LWIR pulses with 4.5 µJ output pulse energy are produced via soliton-like self-compression in a 5 mm thick KrS-5. The experimental results quantitatively agree well with the numerical simulation based on the unidirectional pulse propagation equation. This work shows the experimental feasibility of high-energy, near-single-cycle LWIR light bullet generation in solids.

Estimations of Long-Term nss-SO42- and NO3- Wet Depositions over East Asia by Use of Ensemble Machine-Learning Method.

Wet deposition of non-sea-salt sulfate (nss-SO42-) and nitrate (NO3-), derived from anthropogenic emissions of SO2 and NOx, exerts adverse effects on ecosystems. In this work, an ensemble back-propagation neural network was proposed to estimate the long-term wet depositions of nss-SO42- (2005-2017) and NO3- (2001-2014) over East Asia in 10 km resolution. The R2 values for the 10-fold cross-validation of annual wet depositions of nss-SO42- and NO3- were 0.90 and 0.85, respectively. The hotspots of the wet deposition of these two acidic species span southwestern, central, and eastern China. The molar ratio of NO3- to nss-SO42- increased in 10 out of 12 analyzed East Asian countries from 2005 to 2014, which indicates that the acidity in rainwater shifts from the sulfur type to nitrogen type over most of the regions. The wet deposition on the four ecosystems (forest, grassland, cropland, and freshwater body) was also analyzed. Results showed that the nss-SO42- wet deposition on 25.5% of freshwater bodies in 2015 and NO3- wet deposition on 21.7% of grassland in 2014 exceeded the ecosystem empirical critical loads (25 kg/ha sulfate and 2 kg N/ha) in East Asia. Thus, more stringent and regionally collaborative sulfur and nitrogen emission-control measures are urgently needed to protect the ecosystem of East Asia.

Sewers induce changes in the chemical characteristics, bacterial communities, and pathogen distribution of sewage and greywater.

Sewers may affect the characteristics and bacterial communities of wastewater, and need be studied as they may impact treatment facilities and recycling operations. In this study, the wastewater characteristics and bacterial communities from the inflow and outflow of two sewers (sewage and greywater) were analyzed. The chemical oxygen demand was significantly reduced in the sewage and greywater sewer and the greywater sewer generated less sulfide and methane. Proteobacteria, Bacteroidetes, and Firmicutes as the major phyla in sewage and greywater and sewer biofilms. Sewer conveyance caused changes in the distribution and community interaction of suspended bacteria. Greywater contained abundant water-related pathogenic bacteria (WPB) and some WPB (e.g. Aeromonas, Klebsiella and Shigella) number in greywater were not lower than sewage. Sewers could increase the number of Shigella in sewage and decrease the number of Acinetobacter in greywater. Further treatment or disinfection of greywater collected by sewers was necessary and directly reuse of greywater without treatment should be avoided.

Influences of flow conditions on bacterial communities in sewage and greywater small diameter gravity sewer biofilms.

Small diameter gravity sewers (SDGS) have been applied in rural areas to collect sewage or greywater. Flow conditions in rural SDGS are variable and their influences on bacteria in sewer biofilms are still not clear. To investigate the effect of flow conditions on sewage and greywater SDGS biofilms, six sewage SDGS and six greywater SDGS were operated and Illumina HiSeq sequencing was subsequently performed on sewer biofilms. The results indicate that the predominant bacterial phyla in both sewage and greywater SDGS biofilms were Proteobacteria (63.0% ± 9.3%) and Actinobacteria (26.5% ± 8.8%) and co-presence relationship was the main interaction in SDGS biofilm bacterial communities. Compared with stable flow conditions, variable flow conditions altered the bacterial community of SDGS biofilms from the aspect of bacteria compositions and community interactions and the relative abundance of many bacteria showed significant distinctions between stable and variable flow conditions. In sewage SDGS biofilm, the relative abundance of denitrifying, nitrite-oxidizing, and sulfate-reducing bacteria decreased significantly in variable flow conditions while in greywater SDGS biofilms, nitrite-oxidizing and water-related pathogenic bacteria decreased significantly in variable flow conditions. Influences of flow conditions on predicted bacterial functions were also significant in sewage and greywater SDGS biofilms. Variable flow conditions might be conducive to the reduction of H2S generation and water-related pathogenic bacteria in rural SDGS biofilms.

Design and Experiments of a Water Color Remote Sensing-Oriented Unmanned Surface Vehicle.

Integrated and intelligent in situ observations are important for the remote sensing monitoring of dynamic water environments. To meet the field investigation requirements of ocean color remote sensing, we developed a water color remote sensing-oriented unmanned surface vehicle (WC-USV), which consisted of an unmanned surface vehicle platform with ground control station, data acquisition, and transmission modules. The WC-USV was designed with functions, such as remote controlling, status monitoring, automatic obstacle avoidance, and water and meteorological parameter measurement acquisition, transmission, and processing. The key data acquisition module consisted of four parts: A floating optical buoy (FOBY) for collecting remote sensing reflectance ( R r s ) via the skylight-blocked approach; a water sample autocollection system that can collect 12 1-L bottles for analysis in the laboratory; a water quality measurement system for obtaining water parameters, including Chlorophyll-a (Chl-a), turbidity, and water temperature, among others; and meteorological sensors for measuring wind speed and direction, air pressure, temperature, and humidity. Field experiments were conducted to validate the performance of the WC-USV on 23-28 March 2018 in the Honghu Lake, which is the seventh largest freshwater lake in China. The tests proved the following: (1) The WC-USV performed well in terms of autonomous navigation and obstacle avoidance; (2) the mounted FOBY-derived R r s showed good precision in terms of the quality assurance score (QAS), which was higher than 0.98; (3) the Chl-a and suspended matters (SPM) as ocean color parameters measured by the WC-USV were highly consistent with laboratory analysis results, with determination coefficients (R2) of 0.71 and 0.77, respectively; and (4) meteorological parameters could be continuously and stably measured by WC-USV. Results demonstrated the feasibility and practicability of the WC-USV for automatic in situ observations. The USV provided a new way of thinking for the future development of intelligent automation of the aquatic remote sensing ground verification system. It could be a good option to conduct field investigations for ocean color remote sensing and provide an alternative for highly polluted and/or shallow high-risk waters which large vessels have difficulty reaching.

Characteristics of sewer biofilms in aerobic rural small diameter gravity sewers.

Small diameter gravity sewers (SDGS) are extensively used to collect rural sewage as they are low in cost and quick to construct. However, the characteristics of biofilms in rural SDGS are still not clear. In this study, biofilms characteristics of aerobic rural SDGS were investigated using simulations in a lab under different flow conditions and slopes. Results indicated that the average thickness of aerobic rural SDGS biofilms was in the range of 350-650 µm, decreasing at locations with variable flow and high slopes. Protein was the most abundant substance in extracellular polymeric substance of SDGS biofilms. The most abundant bacteria, Proteobacteria, Actinobacteria, and Bacteroidetes, and functional bacteria showed different distributions when analyzed through Illumina HiSeq sequencing of 16S rRNA. The relative abundances of denitrifying bacteria, nitrite-oxidizing bacteria, and sulfate-reducing bacteria (SRB) were lower during variable flow than during stable flow. High slopes (15‰) decreased SRB presence, which could be used to mitigate H2S accumulation in aerobic SDGS. Overall, this study describes the characteristics of aerobic rural SDGS biofilms and provides valuable suggestions for the optimal design of SDGS based on these characteristics.

Highly-expressed P2X7 receptor promotes growth and metastasis of human HOS/MNNG osteosarcoma cells via PI3K/Akt/GSK3ß/ß-catenin and mTOR/HIF1α/VEGF signaling.

The P2X7 receptor, an ATP-gated ion channel, is critical for cancer cell growth, invasiveness, and angiogenesis. Previous studies indicate that P2X7 regulates osteoblast proliferation and osteodeposition and that high P2X7 expression has a pro-growth effect in osteosarcoma. However, how it functions in osteosarcoma cell growth and metastasis is not clear. Thus, we elucidated molecular mechanisms of P2X7-dependent positive regulation of osteosarcoma cell proliferation, invasion, migration, epithelial to mesenchymal transition (EMT), and angiogenesis using in vitro and in vivo models. We confirm that P2X7 is highly-expressed in human osteosarcoma tumor tissues and HOS/MNNG, MG63, U2OS, SW1353 and SAOS-2 cell lines. P2X7 receptor stimulation enhanced HOS/MNNG and SAOS-2 cell proliferation, migration and invasion; but knockdown of P2X7 expression or receptor inhibition had opposite effects. P2X7 positively regulated glycogen content, epithelial to mesenchymal transition and stemness of HOS/MNNG cells. P2X7 activation promoted PI3K/Akt/GSK3ß/ß-catenin and mTOR/HIF1α/VEGF signaling, thereby mediating pro-tumor effects of osteosarcoma cells. Consistent with data from in vitro experiments, systemic administration of P2X7 agonist induced tumor growth, metastasis and tumor-associated bone destruction in osteosarcoma-bearing nude mice, whereas a P2X7 antagonist reversed these effects. Thus, the P2X7 receptor participates in regulation of osteosarcoma growth and metastasis and we offer evidence that P2X7 may be a promising therapeutic target for treating osteosarcoma.

High-energy mid-infrared intrapulse difference-frequency generation with 5.3% conversion efficiency driven at 3 µm.

Intrapulse difference-frequency generation (IPDFG) is a relatively simple technique to produce few-cycle mid-infrared (MIR) radiations. The conversion efficiency of IPDFG could be potentially improved by using the long driving wavelength to reduce the quantum defect. In this paper, we report a high-energy MIR IPDFG source with a record-high conversion efficiency of up to 5.3%, driven by 3 µm, 35 fs, 10 kHz pulses. The IPDFG output has a 5 µJ pulse energy and 50 mW average power. It spans over a spectral range from 6 to 13.2 µm. A 68 fs of IPDFG pulse width is measured, corresponding to 2.1 cycles, centered at 9.7 µm. The high-energy, two-cycle IPDFG pulses are used to produce a 3-octave supercontinuum in a KRS-5 crystal, spanning from 2 to 16 µm, with a 2.4 µJ pulse energy and a 24 mW average power.