Specialized ovipositor sensilla of Cretaceous wasps (Insecta: Hymenoptera) possibly reveal a unique way of host detection.

Insects have evolved complex sensory systems that are important for feeding, defence and reproduction. Parasitoid wasps often spend much time and effort in searching for concealed hosts with the help of specialized sensilla. However, the early evolution of such behaviour and sensilla is poorly known. We describe two fossil female wasps, †Tichostephanus kachinensis sp. nov. and †Tichostephanus longus sp. nov., from mid-Cretaceous Kachin amber. Phylogenetic analyses based on morphological data retrieved †Tichostephanus as deeply nested within Evanioidea and closely related to extant Gasteruptiidae and Evaniidae. Both of these Cretaceous wasps possess features, e.g. coronal tubercles and flexible ovipositor sheaths, that indicate that they might have laid eggs in wood where their larvae possibly parasitized insect larvae. They have a peculiar and unique 'bottle brush' of sensilla close to the apex of their ovipositor sheaths, which has not been observed in any extant parasitoid wasps. These sensilla comprise many regularly arranged plate-shaped setae, attached in relatively large sockets and with rows of longitudinal ridges. Such specialized sensilla perhaps served to enhance the ability to detect hosts inside wood.

Independent wing reductions and losses among stick and leaf insects (Phasmatodea), supported by new Cretaceous fossils in amber.

BACKGROUND: Phasmatodea (stick and leaf insects) play a central role on the debate regarding wing reduction and loss, and its wings are putative reacquisition from secondarily wingless ancestors based solely on extant species. A pivotal taxon in this respect is the species-poor Timematodea, consisting of approximately 21 wingless extant species, which form the sister group of all remaining winged or wingless stick and leaf insects, the Euphasmatodea. RESULTS: Herein, the new fossils of Timematodea from mid-Cretaceous Kachin amber are reported, with winged and wingless species co-occurring. The palaeogeographic distributions of all fossils of Holophasmatodea are summarized, showing their wide paleo-distributions. The phylogenetic analysis based on morphological characters confirms the earliest-diverging lineage of winged Breviala cretacea gen. et sp. nov. in Timematodea, and the possible relationships among all families of Holophasmatodea. These are critical for the reconstruction of patterns of wing evolution in early Phasmatodea. CONCLUSIONS: The new fossils suggest that Timematodea once had wings, at least during the mid-Cretaceous. The palaeogeographic occurrences imply that Timematodea probably have been widely distributed since at least the Jurassic. The phylogenetic analysis with the ancestral-state reconstruction of wings indicates that the common ancestors of Holophasmatodea were winged, the reductions and losses of wings among Timematodea and Euphasmatodea have occurred independently since at least the Cretaceous, and the reduction or loss of the forewing earlier than the hind wings.

The application of extracellular vesicles in colorectal cancer metastasis and drug resistance: recent advances and trends.

Colorectal cancer (CRC) has high incidence and mortality rates and is one of the most common cancers of the digestive tract worldwide. Metastasis and drug resistance are the main causes of cancer treatment failure. Studies have recently suggested extracellular vesicles (EVs) as a novel mechanism for intercellular communication. They are vesicular particles, which are secreted and released into biological fluids, such as blood, urine, milk, etc., by a variety of cells and carry numerous biologically active molecules, including proteins, nucleic acids, lipids, metabolites, etc. EVs play a crucial part in the metastasis and drug resistance of CRC by delivering cargo to recipient cells and modulating their behavior. An in-depth exploration of EVs might facilitate a comprehensive understanding of the biological behavior of CRC metastasis and drug resistance, which might provide a basis for developing therapeutic strategies. Therefore, considering the specific biological properties of EVs, researchers have attempted to explore their potential as next-generation delivery systems. On the other hand, EVs have also been demonstrated as biomarkers for the prediction, diagnosis, and presumed prognosis of CRC. This review focuses on the role of EVs in regulating the metastasis and chemoresistance of CRC. Moreover, the clinical applications of EVs are also discussed.

Construction of a food-grade gene editing system based on CRISPR-Cas9 and its application in Lactococcus lactis NZ9000.

Clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system has been widely used in gene editing of various organisms. However, food-grade gene editing systems in lactic acid bacteria are still preliminary. Red/ET-dependent homologous recombination or CRISPR-based systems have been developed to gene editing in Lactococcus lactis, but these methods are overall inefficient. In the present study, a recombinant system based on CRISPR/Cas9 technology combined with Red/ET was developed using the plasmid pMG36e derived from Lactococcus lactis. Then, the developed recombinant system was applied to Lactococcus lactis. Knockout efficiency was significantly higher using the developed system (91%). In addition, this system showed the potential to be used as a high-throughput method for hierarchical screening. Finally, a gene-edited strain was obtained, and no antibiotics or exogenous genes were introduced using the developed gene editing system. Thus, the efficient system in lactic acid bacteria was constructed and optimized.

Three-Dimensional-Cultured MSC-Derived Exosome-Hydrogel Hybrid Microneedle Array Patch for Spinal Cord Repair.

Exosomes derived from mesenchymal stem cells (MSCs) have been proven to exhibit great potentials in spinal cord injury (SCI) therapy. However, conventional two-dimensional (2D) culture will inevitably lead to the loss of stemness of MSCs, which substantially limits the therapeutic potency of MSCs exosomes (2D-Exo). Exosomes derived from three-dimensional culture (3D-Exo) possess higher therapeutic efficiency which have wide applications in spinal cord therapy. Typically, conventional exosome therapy that relies on local repeated injection results in secondary injury and low efficiency. It is urgent to develop a more reliable, convenient, and effective exosome delivery method to achieve constant in situ exosomes release. Herein, we proposed a controlled 3D-exohydrogel hybrid microneedle array patch to achieve SCI repair in situ. Our studies suggested that MSCs with 3D-culturing could maintain their stemness, and consequently, 3D-Exo effectively reduced SCI-induced inflammation and glial scarring. Thus, it is a promising therapeutic strategy for the treatment of SCI.

Ferroelectric Domain Reversal Dynamics in LiNbO3 Optical Superlattice Investigated with a Real-Time Monitoring System.

The optical superlattice structure derived from a periodic poling process endows ferroelectric crystals with tunable optical property regulation, which has become one of the most efficient strategies for fabricating high-efficiency optical devices. Achieving a precise superlattice structure has been the main barrier for preparation of specific optical applications due to the unclear dynamics of domain structure regulation. Herein, a real-time monitoring system for the in situ observation of periodic poling of lithium niobate is established to investigate ferroelectric domain reversal dynamics. The formation of reversed domain nuclei, growth, and expansion of the domain are monitored, which is highly related to domain growth dynamics. The nucleation and growth of domain are discussed combined with the monition of domain reversal and the variation of local electric field distribution along with finite element analysis. An electrode configuration with multiholes is proposed to use the local electric field more efficiently and controllably, which could achieve a higher domain nucleus density with high uniformity. Two-mm-thick periodically poled LiNbO3 crystals with high quality are achieved. A nonlinear light conversion from 1064.2 to 3402.4 nm is realized by the single-resonance optical parameter oscillator with a nonlinear optical efficiency up to 26.2%.

Biomaterial Cues Regulated Differentiation of Neural Stem Cells into GABAergic Neurons through Ca2+/c-Jun/TLX3 Signaling Promoted by Hydroxyapatite Nanorods.

Directed differentiation enables the production of a specific cell type by manipulating signals in development. However, there is a lack of effective means to accelerate the regeneration of neurons of particular subtypes for pathogenesis and clinical therapy. In this study, we find that hydroxyapatite (HAp) nanorods promote neural differentiation of neural stem cells due to their chemical compositions. Lysosome-mediated degradation of HAp nanorods elevates intracellular calcium concentrations and accelerates GABAergic neurogenesis. As a mechanism, the enhanced activity of a Ca2+ peak initiated by HAp nanorods leads to the activation of c-Jun and thus suppresses the expression of GABAergic/glutamatergic selection gene TLX3. We demonstrate the capability of HAp nanorods in promoting the differentiation into GABAergic neurons at both molecular and cellular function levels. Given that GABAergic neurons are responsible for various physiological and pathological processes, our findings open up enormous opportunities in efficient and precise stem cell therapy of neurodegenerative diseases.

Does aspirin reduce the incidence, recurrence, and mortality of colorectal cancer? A meta-analysis of randomized clinical trials.

BACKGROUND: Colorectal cancer (CRC) is the third most common diagnosed cancer and the third leading cause of all cancer deaths in the USA. Some evidences are shown that aspirin can reduce the morbidity and mortality of different cancers, including CRC. Aspirin has become a new focus of cancer prevention and treatment research so far; clinical studies, however, found conflicting conclusions of its anti-cancer characteristics. This study is to summarize the latest evidence of correlation between aspirin use and CRC and/or colorectal adenomas. METHODS: Databases were searched to identify randomized controlled trials (RCTs) in the salvage setting. The pooled relative risk (RR) with 95% confidence interval (CI) was used to estimate the effect of aspirin on colorectal cancer and/or colorectal adenomas. Subgroup analysis and sensitivity analysis were also conducted. RESULTS: The result showed that aspirin use was not associated with incidence of CRC (RR 0.97; 95% CI 0.84-1.12; P = 0.66; I2 = 34%), aspirin use was found to be associated with reduced recurrence of colorectal adenomas (RR 0.83; 95% CI 0.72-0.95; P = 0.006; I2 = 63%) and reduced mortality of CRC (RR 0.79; 95% CI 0.64-0.97; P = 0.02; I2 = 14%). Subgroup analysis found a statistically significant association in low dose with a pooled RR of 0.85 (95% CI 0.74-0.99; P = 0.03; I2 = 31%). CONCLUSIONS: This meta-analysis of randomized controlled trial data indicates that aspirin reduces the overall risk of recurrence and mortality of CRC and/or colorectal adenomas. Incidence of CRC was also reduced with low-dose aspirin. The emerging evidence on aspirin's cancer protection role highlights an exciting time for cancer prevention through low-cost interventions. TRIAL REGISTRATION: Clinicaltrials.gov no: CRD42020208852; August 18, 2020; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020208852 ).

Does Famotidine Reduce the Risk of Progression to Severe Disease, Death, and Intubation for COVID-19 Patients? A Systemic Review and Meta-Analysis.

BACKGROUND: Famotidine was reported to potentially provide benefits to Coronavirus Disease 2019 (COVID-19) patients. However, it remains controversial whether it is effective in treating COVID-19. AIMS: This study aimed to explore whether famotidine use is associated with reduced risk of the severity, death, and intubation for COVID-19 patients. METHODS: This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42020213536). A comprehensive search was performed to identify relevant studies up to October 2020. I-squared statistic and Q-test were utilized to assess the heterogeneity. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated through the random effects or fixed effects model according to the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also conducted. RESULTS: Five studies including 36,635 subjects were included. We found that famotidine use was associated with a statistically non-significant reduced risk of progression to severe disease, death, and intubation for Coronavirus Disease 2019 (COVID-19) patients (pooled RR was 0.82, 95% CI = 0.52-1.30, P = 0.40). CONCLUSION: Famotidine has no significant protective effect in reducing the risk of developing serious illness, death, and intubation for COVID-19 patients. More original studies are needed to further clarify whether it is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.

USA carbon neutrality target: Evaluating the role of environmentally adjusted multifactor productivity growth in limiting carbon emissions.

One of the most vital strategies to achieve sustainable development is to target green growth, which is pollution adjusted output growth rate. Since green growth addresses both economic performance and environmental sustainability, it is necessary for sustainable development. To gauge the environmental impact of increased output, researchers use conventional measure of output growth. However, these measures are not adjusted for pollution and hence, do not reflect the true growth performance of the economy. For this purpose, this study aims to investigate the role of green growth in limiting carbon emissions in the USA for the period of 1990-2019. The authors further examine the role of globalization and renewable energy consumption in affecting CO2 emissions of USA. The results show that in the long run, green growth, output, renewable energies, and globalization are important factors in affecting CO2 emissions of USA. The results of frequency causality test show that there is unidirectional causal relationship from output renewable energy consumption, green growth, and globalization to CO2 emissions in the long run and medium run. This study suggests interesting policies for achieving targets of carbon neutrality. There is a dire need to take instant actions to control climate change and to mitigate greenhouse gases (GHGs). To achieve the target of carbon neutrality, a downward adjustment of economic growth is necessary, which will help the country to abate the pollution emissions.

Cretaceous winged stick insects clarify the early evolution of Phasmatodea.

Wingless and shorter winged stick insects are very common today, but most known extinct stick insects had fully developed wings, leading to contentious affinities among the extinct winged and extant groups. We report herein three male winged stick insects, assigned to Pterophasmatidae fam. nov., from mid-Cretaceous Myanmar (Burmese) amber. Pterophasmatidae fam. nov. are regarded as transitional taxa from extinct winged to modern wingless and shorter winged stick insects based on their similar tegmina venation with extinct Susumanioidea and some body features the same as extant Phasmatodea. However, their symmetric phallic organs comprising two consistent phallomeres are different from those of all living groups. Phylogenetic analyses suggest that the extinct winged taxa, including the new family, are the stem groups of modern stick and leaf insects, and all of them constitute the clade of Phasmatodea. New findings indicate winged and wingless stick insects' morphologies diversified significantly during or before the mid-Cretaceous.

Preliminary report of a single-channel applicator in high dose rate afterloading brachytherapy for cervical cancer.

The aim of this study was to evaluate whether a patented single-channel applicator, which was modified from the traditional tandem applicator and wrapped with an oval-shield alloy around the source channel, has the same clinical efficacy and safety as the standard Fletcher-type applicator in high dose rate (HDR) brachytherapy for carcinoma of the cervix. Between December 2011 and February 2017, 299 patients with pathologically confirmed International Federation of Gynecology and Obstetrics (2009) stage Ib2-IVa cervical cancer were recruited to the trial and finished the allocated intervention. Of the first 151 patients, 71 were allocated to the Fletcher group and 80 to the single-channel group, satisfying the criteria for a preliminary analysis. All but 3 patients were treated with concurrent cisplatin chemotherapy and external beam radiotherapy followed by HDR brachytherapy. The 2-year overall survival, progression-free survival, and locoregional failure-free survival was 80.3%, 77.5%, and 78.9%, respectively, for the Fletcher group, and 86.3%, 82.5%, and 83.8%, respectively, for the single-channel group. The seriousness of acute treatment-related toxicities was similar in the 2 groups. The cumulative rate of late rectal complications of grade 3-4 in the Fletcher group and the single-channel group was 2.8% and 2.5%, respectively. The cumulative rate of grade 3 bladder complications was 2.8% for the Fletcher group and 1.3% for the single-channel group. The preliminary results of our study show that the patented single-channel intracavitary applicator might be able to provide protection for the rectum and bladder and seems to have the same clinical efficacy as the standard Fletcher-type 3-channel applicator in HDR brachytherapy for carcinoma of the cervix. This trial was registered with the Chinese Clinical Trial Registry (registration no. ChiCTR-TRC-12002321).

MicroRNA-183 promotes migration and invasion of CD133(+)/CD326(+) lung adenocarcinoma initiating cells via PTPN4 inhibition.

Non-small cell lung cancer (NSCLC) is the most common cancer worldwide and is a leading cause of lung cancer mortality due to early stage metastases. Cancer stem-like cells (CSLCs) or tumor-initiating cells (TICs) are rare subpopulation cells that are responsible for maintaining tumor growth and invasion leading to recurrence and metastasis. Previous studies revealed that miR-183 can mediate the invasiveness and growth of NSCLC. However, the exact role of miR-183 in regulating the biological behavior of CSLCs in NSCLC remains unclear. In the present study, we explored the regulation of protein tyrosine phosphatase non-receptor type 4 (PTPN4) by miR-183 in vitro using luciferase reporter assays, and we further analyzed the effects of miR-183 on the invasiveness of CSLCs in vitro and in vivo using transwell and bioluminescence assays. Following our finding that miR-183 binds to PTPN4 messenger RNA (mRNA) to prevent its translation through the 3'-untranslated region (UTR), we found that overexpression of miR-183 in CSLCs decreased PTPN4 protein levels while inhibition of miR-183 increased PTPN4 protein levels. The suppression of PTPN4 levels in CSLCs by miR-183 paralleled with a significant promotion in their motility in vitro and in vivo, while anti-sense miR-183 increased PTPN4 levels in CSLCs, which paralleled with a significant decrease in their invasiveness. Furthermore, correlation analysis between miR-183 and PTPN4 in clinical samples demonstrated a statistically significant inverse correlation between PTPN4 mRNA levels and miR-183. In brief, our data indicate that miR-183 plays a pro-invasive role by inverse regulation of PTPN4, and this axis may be a new therapeutic target for suppressing the metastatic capability of CSLCs in NSCLC.

LC-UV Determination of Baicalin in Rabbit Plasma and Tissues for Application in Pharmacokinetics and Tissue Distribution Studies of Baicalin after Intravenous Administration of Liposomal and Injectable Formulations.

A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH 3.5; 1 M) to obtain a pure chromatographic peak and high extraction recovery. Chromatographic separation was achieved on a reverse-phase C18 column with a gradient elution at flow rate of 1.0 mL/min. UV absorption was set at 278 nm. Chromatographic response was linear over the ranges of 0.05-10.00 µg/mL in plasma and 0.05-300.00 µg/g in tissues with the limits of quantification of 50.0 ng/mL in plasma and tissues, and the limit of detection of baicalin in bio-samples of 15 ng/mL. The RSD of intra-and inter-day for the biosamples were from 4.19% to 10.84% and from 4.37% to 10.93%, respectively. The accuracy of plasma and tissue samples ranged from 81.6% to 95.2% and 80.8% to 98.4%, respectively. The extraction recoveries ranged from 81.5% to 88.3% for plasma, from 73.1% to 93.2% for tissues, respectively. Baicalin was stable in rabbit biosamples. The validated method was successfully applied to the study of the pharmacokinetics and tissue distribution of baicalin after intravenous administration of liposomal and injectable formulations to rabbits. Compared to baicalin injection, the pharmacokinetics and biodistribution behavior of baicalin was altered significantly in rabbits treated with its liposomes and drug concentration in the lungs was greatly increased.

Development of a HPLC method to determine 5-fluorouracil in plasma: application in pharmacokinetics and steady-state concentration monitoring.

A simple, rapid and sensitive high-power liquid chromatographic (HPLC) method for analysis of 5-fluorouracil (5-FU) in patient plasma was developed and validated to study clinical pharmacokinetics (PK). Plasma sample preparation was processed with ammonium acetate buffer (pH 3.5; 0.01M) followed by liquid-liquid extraction with isopropanol/ethyl acetate (15 : 85, v/v). Extraction recovery ranged from 87.55 to 95.26%. Separation was performed using a C18 column at 25 °C with UV detection at 265 nm. The isocratic mobile phase composed of acetonitrile-ammonium acetate buffer (pH 3.5; 0.01M) (2.5 : 97.5 v/v) at a flow rate of 0.8 mL/min. Retention time was less than 7 minutes. Standard curve was linear between 0.01 - 10 µg/mL and 10 - 100 µg/mL for plasma sample. The limit of quantification was 10 ng/mL. The intra- and interday precision was below 10% (RSD). The accuracy ranged from 85.24 to 104.14%. The analysis method is rapid because it needs neither time-consuming extraction procedures nor complex chromatographic condition. The method was successfully applied to access pharmacokinetics and plasma concentration at steady state (SSC) of 5-FU. The results showed the PK and SSC of 5-FU characterized by a large interpatient variability. To increase therapeutic response and reduce toxicity, we should optimize 5-FU dose by investigating PK behavior to obtain ideal SSC..

Improvement in angular color uniformity of white light-emitting diodes using screen-printed multilayer phosphor-in-glass.

Angular color uniformity (ACU) is a key optical property of white light-emitting diodes (WLEDs) and high ACU is strongly demanded in illumination applications. In this paper, a multilayer phosphor-in-glass (PiG), which can be produced by the screen-printing method, is proposed to improve the ACU of LED packages. The screen-printing method provides a feasible scheme to produce multilayer, various-shaped PiG with a controllable pattern. Angular correlated color temperature (CCT) distributions of the LED packages with multilayer PiG are simulated numerically and measured experimentally. Optical performance of the LED package with optimized three-layer cone-shaped PiG is compared with that of packages with two-layer and one-layer PiG. The experimental measurements indicate that the deviation of angular CCT can be reduced from 761 to 171 K by cone-shaped PiG at average CCT of 6000 K. The results demonstrate that higher angular color uniformity can be achieved by LED packages with multilayer cone-shaped PiG.

Microfluidic Platforms for Real-Time In Situ Monitoring of Biomarkers for Cellular Processes.

Cellular processes are mechanisms carried out at the cellular level that are aimed at guaranteeing the stability of the organism they comprise. The investigation of cellular processes is key to understanding cell fate, understanding pathogenic mechanisms, and developing new therapeutic technologies. Microfluidic platforms are thought to be the most powerful tools among all methodologies for investigating cellular processes because they can integrate almost all types of the existing intracellular and extracellular biomarker-sensing methods and observation approaches for cell behavior, combined with precisely controlled cell culture, manipulation, stimulation, and analysis. Most importantly, microfluidic platforms can realize real-time in situ detection of secreted proteins, exosomes, and other biomarkers produced during cell physiological processes, thereby providing the possibility to draw the whole picture for a cellular process. Owing to their advantages of high throughput, low sample consumption, and precise cell control, microfluidic platforms with real-time in situ monitoring characteristics are widely being used in cell analysis, disease diagnosis, pharmaceutical research, and biological production. This review focuses on the basic concepts, recent progress, and application prospects of microfluidic platforms for real-time in situ monitoring of biomarkers in cellular processes.

Electromagnetic Cellularized Patch with Wirelessly Electrical Stimulation for Promoting Neuronal Differentiation and Spinal Cord Injury Repair.

Although stem cell therapy holds promise for the treatment of spinal cord injury (SCI), its practical applications are limited by the low degree of neural differentiation. Electrical stimulation is one of the most effective ways to promote the differentiation of stem cells into neurons, but conventional wired electrical stimulation may cause secondary injuries, inflammation, pain, and infection. Here, based on the high conductivity of graphite and the electromagnetic induction effect, graphite nanosheets with neural stem cells (NSCs) are proposed as an electromagnetic cellularized patch to generate in situ wirelessly pulsed electric signals under a rotating magnetic field for regulating neuronal differentiation of NSCs to treat SCI. The strength and frequency of the induced voltage can be controlled by adjusting the rotation speed of the magnetic field. The generated pulsed electrical signals promote the differentiation of NSCs into functional mature neurons and increase the proportion of neurons from 12.5% to 33.7%. When implanted in the subarachnoid region of the injured spinal cord, the electromagnetic cellularized patch improves the behavioral performance of the hind limbs and the repair of spinal cord tissue in SCI mice. This work opens a new avenue for remote treatment of SCI and other nervous system diseases.

Non­synchronous bilateral metastatic ovarian cancer originating from small bowel adenocarcinoma with multidisciplinary treatment: A case report.

Primary small bowel adenocarcinoma (SBA) is a rare gastrointestinal cancer with a low incidence of ovarian metastasis. Differential diagnosis of metastatic and primary ovarian cancer is often challenging. The present study reported the case of a 45-year-old woman with jejunal adenocarcinoma who presented with right ovarian, left ovarian, abdominopelvic implant and local recurrent bowel wall metastases successively after primary tumor resection. The ovarian masses of the patient originated from SBA, which was confirmed by immunohistochemical results. Following four comprehensive evaluations by an experienced multidisciplinary team (MDT) during the disease period, the patient underwent four operations, 28 cycles of chemotherapy, 24 cycles of targeted therapy and maintenance therapy for 8 months. As of February 2023, the patient has survived for 73 months and has a high quality of life. It is suggested that when a patient with SBA presents with an ovarian mass, the differential diagnosis between metastatic ovarian cancer and primary ovarian cancer mainly relies on immunohistochemistry. After a comprehensive evaluation by an experienced MDT, surgical resection is the primary treatment for advanced SBA, thus demonstrating some benefits for patients.

3D Gelatin Microsphere Scaffolds Promote Functional Recovery after Spinal Cord Hemisection in Rats.

Spinal cord injury (SCI) damages signal connections and conductions, with the result that neuronal circuits are disrupted leading to neural dysfunctions. Such injuries represent a serious and relatively common central nervous system condition and current treatments have limited success in the reconstruction of nerve connections in injured areas, especially where sizeable gaps are present. Biomaterial scaffolds have become an effective alternative to nerve transplantation in filling these gaps and provide the foundation for simulating the 3D structure of solid organs. However, there remain some limitations with the application of 3D bioprinting for preparation of biomaterial scaffolds. Here, the approach in constructing and testing mini-tissue building blocks and self-assembly, solid 3D gelatin microsphere (GM) scaffolds with multiple voids as based on the convenient preparation of gelatin microspheres by microfluidic devices is described. These 3D GM scaffolds demonstrate suitable biocompatibility, biodegradation, porosity, low preparation costs, and relative ease of production. Moreover, 3D GM scaffolds can effectively bridge injury gaps, establish nerve connections and signal transductions, mitigate inflammatory microenvironments, and reduce glial scar formation. Accordingly, these 3D GM scaffolds can serve as a novel and effective bridging method to promote nerve regeneration and reconstruction and thus recovery of nerve function after SCI.