hnRNPU is required for spermatogonial stem cell pool establishment in mice.

The continuous regeneration of spermatogonial stem cells (SSCs) underpins spermatogenesis and lifelong male fertility, but the developmental origins of the SSC pool remain unclear. Here, we document that hnRNPU is essential for establishing the SSC pool. In male mice, conditional loss of hnRNPU in prospermatogonia (ProSG) arrests spermatogenesis and results in sterility. hnRNPU-deficient ProSG fails to differentiate and migrate to the basement membrane to establish SSC pool in infancy. Moreover, hnRNPU deletion leads to the accumulation of ProSG and disrupts the process of T1-ProSG to T2-ProSG transition. Single-cell transcriptional analyses reveal that germ cells are in a mitotically quiescent state and lose their unique identity upon hnRNPU depletion. We further show that hnRNPU could bind to Vrk1, Slx4, and Dazl transcripts that have been identified to suffer aberrant alternative splicing in hnRNPU-deficient testes. These observations offer important insights into SSC pool establishment and may have translational implications for male fertility.

Advances in volumetric bioprinting.

The three-dimensional (3D) bioprinting technologies are suitable for biomedical applications owing to their ability to manufacture complex and high-precision tissue constructs. However, the slow printing speed of current layer-by-layer (bio)printing modality is the major limitation in biofabrication field. To overcome this issue, volumetric bioprinting (VBP) is developed. VBP changes the layer-wise operation of conventional devices, permitting the creation of geometrically complex, centimeter-scale constructs in tens of seconds. VBP is the next step onward from sequential biofabrication methods, opening new avenues for fast additive manufacturing in the fields of tissue engineering, regenerative medicine, personalized drug testing, and soft robotics, etc. Therefore, this review introduces the printing principles and hardware designs of VBP-based techniques; then focuses on the recent advances in VBP-based (bio)inks and their biomedical applications. Lastly, the current limitations of VBP are discussed together with future direction of research.

A systemic review on Liubao tea: A time-honored dark tea with distinctive raw materials, process techniques, chemical profiles, and biological activities.

Liubao tea (LBT) is a unique microbial-fermented tea that boasts a long consumption history spanning 1500 years. Through a specific post-fermentation process, LBT crafted from local tea cultivars in Liubao town Guangxi acquires four distinct traits, namely, vibrant redness, thickness, aging aroma, and purity. The intricate transformations that occur during post-fermentation involve oxidation, degradation, methylation, glycosylation, and so forth, laying the substance foundation for the distinctive sensory traits. Additionally, LBT contains multitudinous bioactive compounds, such as ellagic acid, catechins, polysaccharides, and theabrownins, which contributes to the diverse modulation abilities on oxidative stress, metabolic syndromes, organic damage, and microbiota flora. However, research on LBT is currently scattered, and there is an urgent need for a systematical recapitulation of the manufacturing process, the dominant microorganisms during fermentation, the dynamic chemical alterations, the sensory traits, and the underlying health benefits. In this review, current research progresses on the peculiar tea varieties, the traditional and modern process technologies, the substance basis of sensory traits, and the latent bioactivities of LBT were comprehensively summarized. Furthermore, the present challenges and deficiencies that hinder the development of LBT, and the possible orientations and future perspectives were thoroughly discussed. By far, the productivity and quality of LBT remain restricted due to the reliance on labor and experience, as well as the incomplete understanding of the intricate interactions and underlying mechanisms involved in processing, organoleptic quality, and bioactivities. Consequently, further research is urgently warranted to address these gaps.

Effects of myonectin on porcine intramuscular adipocyte differentiation and exogenous free fatty acid utilization.

As an important factor secreted by skeletal muscle, myonectin can regulate lipid metabolism and energy metabolism, but its role in the utilization of peripheral free fatty acids (FFAs) by porcine intramuscular fat cells remains to be further investigated. In this study, porcine intramuscular adipocytes were treated with recombinant myonectin and palmitic acid (PA), either alone or in combination, and then were examined for their uptake of exogenous FFAs, intracellular lipid synthesis and catabolism, and mitochondrial oxidation of fatty acids. The results showed that myonectin decreased the area of lipid droplets in intramuscular adipocytes (p < 0.05) and significantly increased (p < 0.05) the expression levels of hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL). Moreover, myonectin can up-regulate the expression of p38 mitogen-activated protein kinase (p38 MAPK). Myonectin significantly promoted the uptake of peripheral FFAs (p < 0.01), improved (p < 0.05) the expression of fatty transport protein 1 (FATP1) and fatty acid binding protein 4 (FABP4) in intramuscular adipocytes. Myonectin also significantly increased (p < 0.05) the expression levels of fatty acid oxidation markers: transcription factor (TFAM), uncoupling protein-2 (UCP2) and oxidative respiratory chain marker protein complex I (NADH-CoQ) in mitochondria of intramuscular adipocytes. In summary, myonectin promoted the absorption, transport, and oxidative metabolism of exogenous FFAs in mitochondria, thereby inhibiting lipid deposition in porcine intramuscular adipocytes.

Asymmetric gene expression and cell-type-specific regulatory networks in the root of bread wheat revealed by single-cell multiomics analysis.

BACKGROUND: Homoeologs are defined as homologous genes resulting from allopolyploidy. Bread wheat, Triticum aestivum, is an allohexaploid species with many homoeologs. Homoeolog expression bias, referring to the relative contribution of homoeologs to the transcriptome, is critical for determining the traits that influence wheat growth and development. Asymmetric transcription of homoeologs has been so far investigated in a tissue or organ-specific manner, which could be misleading due to a mixture of cell types. RESULTS: Here, we perform single nuclei RNA sequencing and ATAC sequencing of wheat root to study the asymmetric gene transcription, reconstruct cell differentiation trajectories and cell-type-specific gene regulatory networks. We identify 22 cell types. We then reconstruct cell differentiation trajectories that suggest different origins between epidermis/cortex and endodermis, distinguishing bread wheat from Arabidopsis. We show that the ratio of asymmetrically transcribed triads varies greatly when analyzing at the single-cell level. Hub transcription factors determining cell type identity are also identified. In particular, we demonstrate that TaSPL14 participates in vasculature development by regulating the expression of BAM1. Combining single-cell transcription and chromatin accessibility data, we construct the pseudo-time regulatory network driving root hair differentiation. We find MYB3R4, REF6, HDG1, and GATAs as key regulators in this process. CONCLUSIONS: Our findings reveal the transcriptional landscape of root organization and asymmetric gene transcription at single-cell resolution in polyploid wheat.

K8sSim: A Simulation Tool for Kubernetes Schedulers and Its Applications in Scheduling Algorithm Optimization.

In recent years, Kubernetes (K8s) has become a dominant resource management and scheduling system in the cloud. In practical scenarios, short-running cloud workloads are usually scheduled through different scheduling algorithms provided by Kubernetes. For example, artificial intelligence (AI) workloads are scheduled through different Volcano scheduling algorithms, such as GANG_MRP, GANG_LRP, and GANG_BRA. One key challenge is that the selection of scheduling algorithms has considerable impacts on job performance results. However, it takes a prohibitively long time to select the optimal algorithm because applying one algorithm in one single job may take a few minutes to complete. This poses the urgent requirement of a simulator that can quickly evaluate the performance impacts of different algorithms, while also considering scheduling-related factors, such as cluster resources, job structures and scheduler configurations. In this paper, we design and implement a Kubernetes simulator called K8sSim, which incorporates typical Kubernetes and Volcano scheduling algorithms for both generic and AI workloads, and provides an accurate simulation of their scheduling process in real clusters. We use real cluster traces from Alibaba to evaluate the effectiveness of K8sSim, and the evaluation results show that (i) compared to the real cluster, K8sSim can accurately evaluate the performance of different scheduling algorithms with similar CloseRate (a novel metric we define to intuitively show the simulation accuracy), and (ii) it can also quickly obtain the scheduling results of different scheduling algorithms by accelerating the scheduling time by an average of 38.56×.

Effects of L-theanine on intestinal morphology, barrier function, and MAPK signaling pathways in diquat-challenged piglets.

This study aimed to explore the protective effects of L-theanine supplementation on the diquat-challenged weaned piglets. A total of 160 weaned piglets were randomly divided into 4 groups using a 2 × 2 two-factor design, there were 4 replicates per group and 10 pigs per replicate. Piglets were fed diets (with 1000 mg/kg L-theanine addition or not), then challenged with diquat or saline on day 7. 21 days after challenge, two pigs from each replicate were selected for sample collection. Results showed that supplement with 1000 mg/kg L-theanine down-regulated the diarrhea rate, serum D-lactate level, tumor necrosis factor-α, and phosphorylation of extracellular regulated protein kinases (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) signaling in pigs without diquat challenge (p < 0.05). While for diquat-challenged piglets, L-theanine addition increased average daily gain, jejunum villus height, and interferon-γ level (p < 0.05). Meanwhile, L-theanine addition decreased the diarrhea rates and mortality, serum D-lactate level, and phosphorylation of ERK and JNK in diquat-challenged pigs (p < 0.05). These results demonstrate that L-theanine pretreatment could alleviate diquat-induced oxidative stress and improve intestinal barrier function in diquat-challenged weaned piglets, which can be attributed to suppression of MAPK phosphorylation signaling pathways.

Posterior Decompression and Fusion with Vertical Pressure Procedure in the Treatment of Multilevel Cervical OPLL with Kyphotic Deformity.

OBJECTIVE: To report the outcomes and feasibility of a new technique to change K-line (-) to K-line (+) via only a posterior approach to treat multilevel non-continuous cervical ossification of the posterior longitudinal ligament (C-OPLL) with kyphotic deformity. METHODS: In this study, 17 consecutive cases of patients who underwent vertical pressure procedure (VP) combined with posterior cervical single-open-door laminoplasty and instrumented fusion from January 1, 2017 to December 31, 2019 were enrolled. The following radiographic parameters: C2-C7 Cobb angle, local Cobb angle, extent of OPLL, and the distance from OPLL to the K-line(DK) were measured and analyzed. Clinically, the JOA score, VAS-N and VAS-A, NDI, and complications were collected from medical records to evaluate the clinical outcomes. RESULTS: All 17 cases shifted from K-line (-) to K-line (+).Comparing the preoperative images to the final follow-up images, the mean C2-7 Cobb angle changed from -6.94° ± 8.30° to 8.18° ± 4.43°, and the local Cobb angle altered from -9.12° ± 8.68° to 6.65° ± 6.11°. The mean DK increased from -2.64 ± 1.52 mm to 3.09 ± 2.19 mm. One patient showed C5 palsy and recovered within 3 months. The mean JOA score increased from 8.88 ± 2.11 to 14.71 ± 1.36. The average NDI decreased from 20.65 ± 7.80 to 8.94 ± 4.93. The mean VAS-N and VAS-A decreased from 3.44 ± 1.80 and 4.69 ± 1.97 to 1.25 ± 0.86 and 1.38 ± 1.16. All patients were followed up for at least 1 year. CONCLUSION: A new technique added to posterior decompression and fusion (PDF), the vertical pressure procedure effectively corrects K-line (-) to K-line (+) and avoids the shortcomings of conventional anterior decompression and fusion (ADF) as well as PDF to provide a relatively safe and adequate decompression, cervical realignment. It pronounced satisfactory clinical outcome for extensive non-continuous OPLL with kyphotic deformity even though OPLL remains ventral to the spinal cord.

Angled Ultrasonic Bone Curette-Assisted Circumferential Decompression for Thoracic Myelopathy Caused by Severely Anterior Ossification.

OBJECTIVE: Thoracic myelopathy caused by severe anterior ossification is often progressive and fails to respond to conservative treatment. Removal of the compressing ossification is the most effective method but is hard to operate. In this study, we describe a novel one-stage posterior circumferential decompressive procedure assisted by an angled ultrasonic bone curette (UBC) for thoracic myelopathy caused by severe anterior ossification and evaluate its safety and efficacy. METHODS: The current study enrolled 15 consecutive patients (five men and 10 women) with thoracic myelopathy caused by severely anterior ossification between January 2017 and December 2019. All patients underwent posterior circumferential decompression assisted by angled UBC and segmental instrumentation with interbody fusion. At the time of surgery, the average age was 58.6 ± 6.3 years (47-70 years). Before and after surgery, the patient data, clinical manifestation, operative levels, blood loss, operative time, perioperative complications, Japanese Orthopaedic Association (JOA) score were recorded and analyzed retrospectively. RESULTS: All patients had successful one-stage posterior circumferential decompression to remove anterior ossifications directly. There were 12 cases of OPLL, two cases of a calcified giant herniated disc, and one case of osteophyte. The average operation time was 153.4 ± 53.4 min (77-242 min), with a mean blood loss of 463.5 ± 155.8 mL (240-780 mL). The average length of stay in the hospital was 14.3 ± 4.7 days (9-25 days) and the mean follow-up duration was 20.8 ± 8.8 months (12-39 months). Almost all patients had subjective improvement in motor power and gait. The average preoperative JOA score was 4.5 ± 1.6, which improved to 9.0 ± 1.8 at the final follow-up. Postoperative differences in the overall JOA scores showed significant improvement (F = 105.446, p < 0.01). The overall recovery rate at the final examination scored 70.9% ± 25.0%. According to Hirabayashi's classification, eight cases were rated as excellent, four as good, two as fair, and one as unchanged. No patient was graded as deteriorated. Two patients (13.3%) experienced intraoperative cerebrospinal fluid leakage, while two cases (13.3%) experienced unilateral intercostal neuralgia, and only one (6.7%) encountered acute neurological deterioration. All these patients were treated conservatively and their neurological function improved significantly. At the follow-up, there was no evidence of neurological deterioration. CONCLUSION: Circumferential decompression assisted by angled UBC can preserve more posterior elements of the involved levels, maintaining an intact pleura and reducing the operation time and blood loss for thoracic myelopathy caused by severe anterior ossification. It is a safe, effective, and technically feasible method to provide surgeons with a new option for thoracic spinal circumferential decompression.

Analysis of the clinical effect of the concept of "shoulder preservation" in the treatment of proximal humeral fractures: a retrospective cohort study of 66 patients.

BACKGROUND: The three- and four-part fractures of the proximal humerus are often combined with rotator cuff injury, and shoulder joint replacement is often selected clinically. The concept of "shoulder preservation" can greatly restore the function of the shoulder joint through internal fixation of the proximal humerus fracture and rotator cuff suture. This study investigated the clinical effect of the concept of "shoulder preservation" in the treatment of three- and four-part fractures of the proximal humerus. METHODS: We conducted a retrospective analysis of 66 patients with proximal humeral fractures (PHFs) who were treated at the Affiliated Hospital of Qinghai University between 2016 and 2019. The patients were divided into 3 groups according to the Neer fracture classification system, and the fracture healing time of the 3 groups was compared. A visual analog scale (VAS) was used to evaluate the pain, and the Neer score was used to evaluate shoulder joint function. RESULTS: The operations were successfully completed and the 3 groups of patients were compared in pairs. All incisions healed by first intention after operation, and no early complications occurred. The average follow-up time was 18 months. All fractures had healed. The VAS score of the 3 groups of patients was 1.5±0.5 at 1 month after operation and 1.0±0.5 at the final follow-up, which was significantly improved compared with preoperative scores, although the difference was not statistically significant (P>0.05). The Neer scores of the first group of patients at 1, 3, and 9 months postsurgery were higher than those of the second and third groups, and the difference was statistically significant (P<0.05). There was no significant difference among the 3 groups in Neer score 12 months after the operation (P>0.05). CONCLUSIONS: Proximal humeral internal locking osteosynthesis system (PHILOS) fixation + rotator cuff suture is a reliable treatment method involving a simple operation, firm fixation, and good postoperative recovery. It can restore shoulder joint function to the greatest extent, but it also has some shortcomings, including slow recovery time.

Experimental and numerical investigation of TVOC concentrations and ventilation dilution in enclosed train cabin.

Air pollution in trains is an important factor threatening human health, which has attracted more and more attention in the worldwide public health researches. In this study, one cabin of a fully enclosed train was taken as an example to conduct experimental and numerical research on pollution level and distribution characteristic of total volatile organic compound (TVOC). The results show that when the average emission rate under daily environmental conditions was taken as the reference, TVOC concentration in the cabin exceeded the limit level of Chinese Indoor Air Quality Standard by more than 4 times. The obvious pollutants accumulative phenomenon could be found at bottoms and corners under the action of airflow. Setting air inlets at the roof of the train, mean age of air ranged from 30 s to 50 s in the breathing area. The concentration of pollutants was the lowest at 2.5-5 m from the center point of the cabin structure, and the ventilation efficiency was the highest. The introduction of clean fresh air could effectively eliminate pollutants. When the complete displacement ventilation rates were 51.4 h-1 and 28.6 h-1, the removal efficiency of pollutants was about 0.85 and 0.48 mg/m3 per minute, respectively. This study was helpful to the improvement and optimization design of air quality and ventilation mode in trains.

Surgical Management for Posterior Atlantoaxial Dislocation without Fracture and Atlantoaxial Dynamic Test to Confirm the Integrity of the Transverse Ligament: A Case Report.

BACKGROUND: Traumatic posterior atlantoaxial dislocation (PAAD) without fracture of the odontoid process is a rare injury. Closed reduction by skull traction under C-arm fluoroscopic guidance and open reduction have been reported previously for the treatment of PAAD. OBJECTIVE: To report a rare case of PAAD without fracture treated by closed manual reduction and posterior fixation. To provide a new method-atlantoaxial dynamic test-for confirming the integrity of the transverse ligament after reduction and evaluate the ideal treatment strategy for traumatic PAAD without fracture of the odontoid process or rupture of the transverse ligament. METHOD: A 54-year-old woman was riding in the passenger seat when her vehicle was rear-ended by a car. X-ray and computed tomography (CT) scans were used to diagnose PAAD without a related fracture. Closed manual reduction under C-arm fluoroscopy was performed after applying general anesthesia via sober intubation, and the integrity of the transverse ligament was confirmed by the atlantoaxial dynamic test with C-arm fluoroscopy. Then, pedicle screw internal fixation via the posterior approach was applied to maintain atlantoaxial stability. RESULTS: The procedure was performed uneventfully, and the patient was able to move out of bed on the first day after surgery with Philadelphia cervical gear. During a 2-year follow-up period, imaging data demonstrated no instability of the atlantoaxial complex. CONCLUSION: Closed manual reduction under C-arm fluoroscopy is an easy and effective method for PAAD. The integrity of the transverse ligament can be confirmed by C-arm fluoroscopy through the atlantoaxial dynamic test after reduction. Pedicle screw internal fixation via the posterior approach can provide sufficient stability.

Quantum limited timing jitter of soliton molecules in a mode-locked fiber laser.

Soliton molecules in mode-locked lasers are expected to be ideal self-organization patterns, which warrant stability and robustness against perturbations. However, recent ultra-high resolution optical cross-correlation measurements uncover an intra-molecular timing jitter, even in stationary soliton molecules. In this work, we found that the intra-molecular timing jitter has a quantum origin. Numerical simulation indicates that amplified spontaneous emission (ASE) noise induces a random quantum diffusion for soliton pulse timing, which cannot be compensated by soliton binding mechanism. By suppressing indirectly coupled timing jitter at close-to-zero cavity dispersion, a record-low 350 as rms intra-soliton-molecular jittering is obtained from an Er-fiber laser in experiment. This work provides insight into the fundamental limits for the instability of multi-soliton patterns.

The web-based multiplex PCR primer design software Ultiplex and the associated experimental workflow: up to 100- plex multiplicity.

BACKGROUND: A large number of variants have been employed in various medical applications, such as providing medication instructions, disease susceptibility testing, paternity testing, and tumour diagnosis. A high multiplicity PCR will outperform other technologies because of its lower cost, reaction time and sample consumption. To conduct a multiplex PCR with higher than 100 plex multiplicity, primers need to be carefully designed to avoid the formation of secondary structures and nonspecific amplification between primers, templates and products. Thus, a user-friendly, highly automated and highly user-defined web-based multiplex PCR primer design software is needed to minimize the work of primer design and experimental verification. RESULTS: Ultiplex was developed as a free online multiplex primer design tool with a user-friendly web-based interface ( http://ultiplex.igenebook.cn ). To evaluate the performance of Ultiplex, 294 out of 295 (99.7%) target primers were successfully designed. A total of 275 targets produced qualified primers after primer filtration, and 271 of those targets were successfully clustered into one compatible PCR group and could be covered by 108 primers. The designed primer group stably detected the rs28934573(C > T) mutation at lower than a 0.25% mutation rate in a series of samples with different ratios of HCT-15 and HaCaT cell line DNA. CONCLUSION: Ultiplex is a web-based multiplex PCR primer tool that has several functions, including batch design and compatibility checking for the exclusion of mutual secondary structures and mutual false alignments across the whole genome. It offers flexible arguments for users to define their own references, primer Tm values, product lengths, plex numbers and tag oligos. With its user-friendly reports and web-based interface, Ultiplex will provide assistance for biological applications and research involving genomic variants.

Performance Analysis of the Technology of High-Temperature Boiler Feed Water to Recover the Waste Heat of Mid-Low-Temperature Flue Gas.

In coal-fired power plants, most of the working fluids used in a mid-low-temperature flue gas waste heat recovery system (FGWHRS) are low-temperature boiler supply air or condensate water in the flue gas condenser. This is prone to cause low-temperature corrosion, as the system temperature is lower than the acid dew point of the flue gas. In this study, an experimental apparatus was set up at the entrance of the desulfurization tower of a 330 MW unit in Xinjiang, China, which uses the technology of high-temperature boiler feed water (above 80 °C) to recover the waste heat of mid-low-temperature flue gas. The heat exchange performance of the mid-low-temperature FGWHRS was evaluated under different working conditions, and the optimal input parameters of the system for each considered working condition are given based on the analysis. It was found that the low-temperature corrosion in the system could be avoided using this technology. To eliminate low-temperature corrosion, the lowest temperature for the inlet water was predicted to be 69 °C in our study via curve fitting based on the experimental data. The results could provide a theoretical basis and engineering guidance for determining the best heat recovery strategy of mid-low-temperature FGWHRS.

A Multiepitope Peptide, rOmp22, Encapsulated in Chitosan-PLGA Nanoparticles as a Candidate Vaccine Against Acinetobacter baumannii Infection.

BACKGROUND: The development of vaccines is a promising and cost-effective strategy to prevent emerging multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. The purpose of this study was to prepare a multiepitope peptide nanovaccine and evaluate its immunogenicity and protective effect in BALB/c mice. METHODS: The B-cell and T-cell epitopes of Omp22 from A. baumannii were predicted using bioinformatics methods and identified by immunological experiments. The optimal epitopes were conjugated in series by 6-aminocaproic acid and chemically synthesized multiepitope polypeptide rOmp22. Then, rOmp22 was encapsulated by chitosan (CS) and poly (lactic-co-glycolic) acid (PLGA) to prepare CS-PLGA-rOmp22 nanoparticles (NPs). The immunogenicity and immunoprotective efficacy of the vaccine were evaluated in BALB/c mice. RESULTS: CS-PLGA-rOmp22 NPs were small (mean size of 272.83 nm) with apparently spherical structures, positively charged (4.39 mV) and nontoxic to A549 cells. A high encapsulation efficiency (54.94%) and a continuous slow release pattern were achieved. Compared with nonencapsulated rOmp22, CS-PLGA-rOmp22 immunized BALB/c mice induced higher levels of rOmp22-specific IgG in serum and IFN-γ in splenocyte supernatant. Additionally, lung injury and bacterial burdens in the lung and blood were suppressed, and potent protection (57.14%-83.3%) against acute lethal intratracheal A. baumannii challenge was observed in BALB/c mice vaccinated with CS-PLGA-rOmp22. CONCLUSION: CS-PLGA-rOmp22 NPs elicited specific IgG antibodies, Th1 cellular immunity and protection against acute lethal intratracheal A. baumannii challenge. Our results indicate that this nanovaccine is a desirable candidate for preventing A. baumannii infection.

Injectable In Situ Self-Cross-Linking Hydrogels Based on Hemoglobin, Carbon Quantum Dots, and Sodium Alginate for Real-Time Detection of Wound Bacterial Infection and Efficient Postoperative Prevention of Tumor Recurrence.

Postoperative wound repair of solid tumors resection, which is afflicted by the complex tumor microenvironment (TME) and associated with the bacterial infection, is worsening and demands prompt solutions. Meanwhile, the tumor recurrence is frequently seen during the subsequent treatment due to intraoperative bleeding. For effective postoperative cancer therapy, nanoscale carriers occur as innovative and sensitive tools for monitoring the wound state, avoiding bacterial infection, and restraining tumor recurrence. Herein, a multifunctional sodium alginate (SA) hydrogel immobilizing hemoglobin (Hb) and pH-sensitive fluorescent changing carbon quantum dots (CQDs) is rationally designed. The multifunctionalization of obtained alginate@hemoglobin@CQDs hydrogel (SA@Hb@CQDs) simultaneously consists of detection, hemostasis, and chemodynamic therapy (CDT) with monitoring of wound pH based on CQDs, stanching triggered from SA hydrogel, and Fenton reaction induced by Hb. We demonstrated that SA@Hb@CQDs can stop bleeding quickly, collect wound status information in real-time, and avert bacterial infection as well as inhibit local tumor recurrence effectively. Therefore, our work provides a promising combination approach for postoperative tumor therapy.

Metabolic and transcriptomic analysis related to flavonoid biosynthesis during the color formation of Michelia crassipes tepal.

Michelia crassipes is the only plant with purple flowers amongst Michelia species, and its tepals exhibit an obvious color change from green to purple. In this study, a combination of metabolic and transcriptomic analyses was conducted at three stages of tepals in Michelia crassipes: green tepal, purple spot-containing tepal, and totally purple tepal. Several classes of flavonoid compounds were detected and cyanidin 3-rutinoside and delphinidin 3-glucoside were the major anthocyanins underlying the purple color formation, along with co-pigmentation of flavone compounds represented by luteolin derivatives and flavonol compounds represented by kaempferol and quercetin derivatives. Transcriptome analysis revealed up-regulation of genes encoding enzymes involved in the conversion of phenylpropanoid for flavonoid biosynthesis in Stage 1 vs. Stage 2, whereas up-regulation of most flavonoid biosynthesis genes was observed in Stage 1 vs. Stage 3. MYB, bHLH, and WD40 isoforms, as well as other classes of transcriptional factors, also exhibited differential expression. In addition, differentially expressed genes putatively related to the transport of flavonoids were also identified. The results of the current study provide insight into the regulatory mechanism underlying the color transition from green to purple in Michelia crassipes tepals and describe a complicated network involving PAL, transporter genes, and transcription factors, specifically responsible for the emergence of purple color in Stage 1 vs. Stage 2.

Period2 gene regulates diurnal changes of nasal symptoms in an allergic rhinitis mouse model.

BACKGROUND: Allergic rhinitis (AR) symptoms exhibit prominent 24-hour variations associated with the biological clock. Although endogenous glucocorticoids synchronize circadian oscillator in the nasal mucosa, the precise mechanism of AR remains unclear. Therefore, using a mouse model, we investigated the association between circadian-clock genes and AR symptoms at various time-points. METHODS: Based on the rhythmic secretion of corticosterone levels, we chose 2 time-points, ZT4 (10:00 AM) and ZT16 (10:00 PM), to observe dynamic changes of nasal symptoms, immunologic responses, and circadian-clock gene period (Per) expressions. RESULTS: In the AR group, nasal symptom scores at ZT4 were significantly higher than at ZT16, with a greater increase in eosinophils, mast cells, and total immunoglobulin E levels at ZT4. The scores had a negative correlation with fluctuation of corticosterone levels. T-helper 1 (Th1) cell counts and interferon-γ levels decreased significantly at ZT4 compared with ZT16 in the AR group, whereas Th2 cells; Th17 cells; and interleukin (IL)-4, -13, and -17A levels increased significantly at ZT4 compared with ZT16. Furthermore, Per2 gene expression levels were attenuated at ZT4 and elevated at ZT16, but correlated negatively with Th2 and Th17 responses associated with Gata3 and Rorγt expression levels that were enhanced at ZT4 and reduced at ZT16 in the AR group. CONCLUSION: Our results suggest that the Per2 gene may influence diurnal variations of AR symptom severity, partially through its possible anti-inflammatory effect on the circadian regulation of GATA3 and RORγt levels in immune cells. This further demonstrates the neural-immune-endocrinal mechanism of circadian rhythm in AR and sheds new light on chronotherapeutic approaches to AR.

Design a novel integrated screw for minimally invasive atlantoaxial anterior transarticular screw fixation: a finite element analysis.

PURPOSE: To design a new type of screw for minimally invasive atlantoaxial anterior transarticular screw (AATS) fixation with a diameter that is significantly thicker than that of traditional screws, threaded structures at both ends, and a porous metal structure in the middle. The use of a porous metal structure can effectively promote bone fusion and compensate for the disadvantages of traditional AATSs in terms of insufficient fixation strength and difficulty of bone fusion. The biomechanical stability of this screw was verified through finite element analysis. This instrument may provide a new surgical option for the treatment of atlantoaxial disorders. METHODS: According to the surgical procedure, the new type of AATS was placed in a three-dimensional atlantoaxial model to determine the setting of relevant parameters such as the diameter, length, and thread to porous metal ratio of the structure. According to the results of measurement, the feasibility and safety of the new AATS were verified, and a representative finite element model of the upper cervical vertebrae was chosen to establish, and the validity of the model was verified. Then, finite element-based biomechanical analysis was performed using three models, i.e., atlantoaxial posterior pedicle screw fixation, traditional atlantoaxial AATS fixation, and atlantoaxial AATS fixation with the new type of screw, and the biomechanical effectiveness of the novel AATS was verified. RESULTS: By measuring the atlantoaxial parameters, the atlantoaxial CT data of the representative 30-year-old normal adult male were selected to create a personalized 3D printing AATS screw. In this case, the design parameters of the new screw were determined as follows: diameter, 6 mm; length of the head thread structure, 10 mm; length of the middle porous metal structure, 8 mm (a middle porous structure containing an annular cylinder ); length of the tail thread structure, 8 mm; and total length, 26 mm. Applying the same load conditions to the atlantoaxial complex along different directions in the established finite element models of the three types of atlantoaxial fusion modes, the immediate stability of the new AATS is similar with Atlantoaxial posterior pedicle screw fixation.They are both superior to traditional atlantoaxial anterior screw fixation.The maximum local stress on the screw head in the atlantoaxial anterior surgery was less than those of traditional atlantoaxial anterior surgery. CONCLUSIONS: By measuring relevant atlantoaxial data, we found that screws with a larger diameter can be used in AATS surgery, and the new AATS can make full use of the atlantoaxial lateral mass space and increase the stability of fixation. The finite element analysis and verification revealed that the biomechanical stability of the new AATS was superior to the AATS used in traditional atlantoaxial AATS fixation. The porous metal structure of the new AATS may promote fusion between atlantoaxial joints and allow more effective bone fusion in the minimally invasive anterior approach surgery.