Accelerating the design of pili-enabled living materials using an integrative technological workflow.

Bacteria can be programmed to create engineered living materials (ELMs) with self-healing and evolvable functionalities. However, further development of ELMs is greatly hampered by the lack of engineerable nonpathogenic chassis and corresponding programmable endogenous biopolymers. Here, we describe a technological workflow for facilitating ELMs design by rationally integrating bioinformatics, structural biology and synthetic biology technologies. We first develop bioinformatics software, termed Bacteria Biopolymer Sniffer (BBSniffer), that allows fast mining of biopolymers and biopolymer-producing bacteria of interest. As a proof-of-principle study, using existing pathogenic pilus as input, we identify the covalently linked pili (CLP) biosynthetic gene cluster in the industrial workhorse Corynebacterium glutamicum. Genetic manipulation and structural characterization reveal the molecular mechanism of the CLP assembly, ultimately enabling a type of programmable pili for ELM design. Finally, engineering of the CLP-enabled living materials transforms cellulosic biomass into lycopene by coupling the extracellular and intracellular bioconversion ability.

Understanding the Tail Current Behavior of Electroactive Biofilms Realizes the Rapid Measurement of Biochemical Oxygen Demand.

The use of microbial electrochemical sensors, with electroactive biofilms (EABs) as sensing elements, is a promising strategy to timely measure the biochemical oxygen demand (BOD) of wastewater. However, accumulation of Coulombic yield over a complete degradation cycle is time-consuming. Therefore, understanding the correlation between current output and EAB metabolism is urgently needed. Here, we recognized a tail stage (TS) on a current-time curve according to current increase rate─a period with the least electron harvesting efficiency. EAB adopted a series of metabolic compensation strategies, including slow metabolism of residual BOD, suspended growth, reduced cell activity, and consumption of carbon storage polymers, to cope with substrate deficiency in TS. The supplementary electrons provided by the decomposition of glycogen and fatty acid polymers increased the Coulombic efficiencies of TS to >100%. The tail current produced by spontaneous metabolic compensation showed a trend of convergent exponential decay, independent of BOD concentration. Therefore, we proposed the TS prediction model (TSPM) to predict Coulombic yield, which shortened BOD measurement time by 96% (to ∼0.5 h) with deviation <4 mg/L when using real domestic wastewater. Our findings on current output in TS give insights into bacterial substrate storage and consumption, as well as regulation in substrate-deficient environment, and provide a basis for developing BOD sensors.

Ectopic Activation of Fgf8 in Dental Mesenchyme Causes Incisor Agenesis and Molar Microdontia.

Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia.

Tooth intentional replantation from 1964 to 2023: A bibliometric analysis.

BACKGROUND/AIM: There is no thorough overview of intentional tooth replantation techniques. We performed a bibliometric analysis of the development of intentional tooth replantation. MATERIALS AND METHODS: A comprehensive search of the Web of Science and SCOPUS databases was conducted in February 2023. Original articles and reviews of human studies with "intentional replantation" or synonyms in the titles, abstracts, or keywords were included. A descriptive analysis of bibliographic data, co-occurrence analysis, and coupling of publications was performed. Multivariate analysis was used to explore the bibliometric parameters associated with the citation counts. RESULTS: The study included 171 papers, which were co-authored by 500 individuals affiliated with 217 institutions from 28 countries/regions. The USA contributed the greatest number of publications, followed by China, and Japan. The USA had 694 citations, followed by Japan (210), and Turkey (210). The Journal of Endodontics and Dental Traumatology contributed the most citations. Five directions for future research were identified based on the coupling relationships of publications, including "managing vertical root fractures with adhesive resin using the intentional replantation technique," "intentional replantation for periodontally hopeless or endodontically compromised teeth," "intentional replantation for treating abnormalities of morphological development," "outcomes and prognosis factors of intentional replantation," and "treating root replacement resorption by intentional replantation." Multivariate analysis showed that the publication year, Journal Citation Reports ranking of journals, study design, and disease type were predictors of citation counts. CONCLUSIONS: This bibliometric analysis provides a comprehensive description of the intentional replantation technique. The USA published the greatest volume of papers and generated the most citations. The Journal of Endodontics and Dental Traumatology are considered the most influential. The Journal Citation Reports journal ranking (Q1, Q2), study design (case reports, cohort studies), and disease type (crown root fractures) were associated with the citation counts.

Dual Stealth Functional Immuno-magnetic Nanoparticles for High-Performance Isolation of Circulating Tumor Cells.

As a biomarker of hepatocellular carcinoma (HCC) biopsy, circulating tumor cells (CTCs) are often used in the diagnosis of cancer and treatment guidance. For CTCs detection, immuno-magnetic nanoparticles (IMNs) are one of the most commonly used platforms. However, the nonspecific adsorption of proteins and non-tumor cells weakens the performance of IMNs to capture CTCs. In this work, we developed an IMNs platform which was constructed by a biomimetic protein corona precoating and a polyethylene glycol (PEG) spacer to form the PEG and corona-coated IMNs (IP-CMNs). Due to the dual stealth effect of protein corona precoating and PEG spacer, the nonspecific protein adsorption and cell binding of P-CMNs could reduce by ∼5.5- and ∼5.4-fold, respectively, compared with those of unmodified particles. Furthermore, the PEG spacer could not only reduce the interaction between IP-CMNs and leukocytes but also enhance the capture performance toward tumor cells. By using artificial blood samples, the capture efficiency of IP-CMNs toward rare CTCs was found to be 88.3%, while it was 70.5% by using commercial IMNs. Finally, CTCs were successfully isolated in all HCC patient blood samples (7/7) using IP-CMNs. These results provide insight into the use of the multifunctional nanoplatform as a useful tool for CTCs detection.

Material Flow Analysis of Dysprosium in the United States.

Dysprosium (Dy) is increasingly being adopted in various clean energy products around the world, intriguing many nations' interests in its availability. However, since data are inaccessible, crucial information about Dy supplies and demands across products and countries remains incomplete. To fill these knowledge gaps, we performed a dynamic bottom-up material flow analysis of Dy, taking the United States (1987-2018) as a case. The results show that the United States (US) domestic demands experienced a growing trend (by 45-fold) with fluctuation and several shifts among applications, primarily owing to technological advancement. A large imbalance (80 times) exists between domestic mineral supplies and market demands, resulting in significant import dependency, with the net import reliance of alloys, chemicals, finished products, and concentrates being 97, 44, 40, and 31%, respectively. Dy is mainly imported as finished products (55.7%) and alloys (43.2%), with concentrates (0.4%) and chemicals (0.7%) accounting for less than 2%. This import dependency may result from fragmentation of the US supply chains because of the stricter environmental regulations on upstream industries and reshoring of the downstream industries. These findings suggest that rare-earth mineral production in the US is about to restart, and it is important for industries to seek international collaboration to boost product competition.

A quantitative clinical evaluation of simultaneous reconstruction of attenuation and activity in time-of-flight PET.

BACKGROUND: The maximum likelihood activity and attenuation (MLAA) reconstruction algorithm has been proposed to jointly estimate tracer activity and attenuation at the same time, and proven to be a promising solution to the CT attenuation correction (CT-AC) artifacts in PET images. This study aimed to perform a quantitative evaluation and clinical validation of the MLAA method. METHODS: A uniform cylinder phantom filled with 18F-FDG solution was scanned to optimize the reconstruction parameters for the implemented MLAA algorithm. 67 patients who underwent whole-body 18F-FDG PET/CT scan were retrospectively recruited. PET images were reconstructed using MLAA and clinical standard OSEM algorithm with CT-AC (CT-OSEM). The mean and maximum standardized uptake values (SUVmean and SUVmax) in regions of interest (ROIs) of organs, high uptake lesions and areas affected by metal implants and respiration motion artifacts were quantitatively analyzed. RESULTS: In quantitative analysis, SUVs in patient's organ ROIs between two methods showed R2 ranging from 0.91 to 0.98 and k ranging from 0.90 to 1.06, and the average SUVmax and SUVmean differences between two methods were within 10% range, except for the lung ROI, which was 10.5% and 16.73% respectively. The average SUVmax and SUVmean differences of a total of 117 high uptake lesions were 7.25% and 7.10% respectively. 20 patients were identified to have apparent respiration motion artifacts in the liver in CT-OSEM images, and the SUVs differences between two methods measured at dome of the liver were significantly larger than measured at middle part of the liver. 10 regions with obvious metal artifacts were identified in CT-OSEM images and the average SUVmean and SUVmax differences in metal implants affected regions were reported to be 52.90% and 56.20% respectively. CONCLUSIONS: PET images reconstructed using MLAA are clinically acceptable in terms of image quality as well as quantification and it is a useful tool in clinical practice, especially when CT-AC may cause respiration motion and metal artifacts. Moreover, this study also provides technical reference and data support for the future iteration and development of PET reconstruction technology of SUV accurate quantification.

Deficiency of Fam20b-Catalyzed Glycosaminoglycan Chain Synthesis in Neural Crest Leads to Cleft Palate.

Cleft palate is one of the most common birth defects. Previous studies revealed that multiple factors, including impaired intracellular or intercellular signals, and incoordination of oral organs led to cleft palate, but were little concerned about the contribution of the extracellular matrix (ECM) during palatogenesis. Proteoglycans (PGs) are one of the important macromolecules in the ECM. They exert biological functions through one or more glycosaminoglycan (GAG) chains attached to core proteins. The family with sequence similarity 20 member b (Fam20b) are newly identified kinase-phosphorylating xylose residues that promote the correct assembly of the tetrasaccharide linkage region by creating a premise for GAG chain elongation. In this study, we explored the function of GAG chains in palate development through Wnt1-Cre; Fam20bf/f mice, which exhibited complete cleft palate, malformed tongue, and micrognathia. In contrast, Osr2-Cre; Fam20bf/f mice, in which Fam20b was deleted only in palatal mesenchyme, showed no abnormality, suggesting that failed palatal elevation in Wnt1-Cre; Fam20bf/f mice was secondary to micrognathia. In addition, the reduced GAG chains promoted the apoptosis of palatal cells, primarily resulting in reduced cell density and decreased palatal volume. The suppressed BMP signaling and reduced mineralization indicated an impaired osteogenesis of palatine, which could be rescued partially by constitutively active Bmpr1a. Together, our study highlighted the key role of GAG chains in palate morphogenesis.

Cellulose-degrading bacteria improve conversion efficiency in the co-digestion of dairy and chicken manure by black soldier fly larvae.

Black soldier fly larvae (BSFL) have potential utility in converting livestock manure into larval biomass as a protein source for livestock feed. However, BSFL have limited ability to convert dairy manure (DM) rich in lignocellulose. Our previous research demonstrated that feeding BSFL with mixtures of 40% dairy manure and 60% chicken manure (DM40) provides a novel strategy for significantly improving their efficiency in converting DM. However, the mechanisms underlying the efficient conversion of DM40 by BSFL are unclear. In this study, we conducted a holistic study on the taxonomic stucture and potential functions of microbiota in the larval gut and manure during the DM and DM40 conversion by BSFL, as well as the effects of BSFL on cellulosic biodegradation and biomass production. Results showed that BSFL can consume cellulose and other nutrients more effectively and harvest more biomass in a shorter conversion cycle in the DM40 system. The larval gut in the DM40 system yielded a higher microbiota complexity. Bacillus and Amphibacillus in the BSFL gut were strongly correlated with the larval cellulose degradation capacity. Furthermore, in vitro screening results for culturable cellulolytic microbes from the larval guts showed that the DM40 system isolated more cellulolytic microbes. A key bacterial strain (DM40L-LB110; Bacillus subtilis) with high cellulase activity from the larval gut of DM40 was validated for potential industrial applications. Therefore, mixing an appropriate proportion of chicken manure into DM increased the abundance of intestinal bacteria (Bacillus and Amphibacillus) producing cellulase and improved the digestion ability (particularly cellulose degradation) of BSFL to cellulose-rich manure through changes in microbial communities composition in intestine. This study reveals the microecological mechanisms underlying the high-efficiency conversion of cellulose-rich manure by BSFL and provide potential applications for the large-scale cellulose-rich wastes conversion by intestinal microbes combined with BSFL.

Clinical applications and outcomes of the surgical tooth extrusion technique: A bibliometric analysis from 1982 to 2023.

STATEMENT OF PROBLEM: The surgical extrusion technique has been advocated for severely damaged teeth as well as for intruded and unerupted teeth. However, a quantitative literature analysis is lacking. PURPOSE: The purpose of this bibliometric analysis was to provide a comprehensive overview of surgical extrusion, assess the applications and outcomes, and evaluate topics for future research. MATERIAL AND METHODS: An electronic search was conducted in leading databases in April 2023. Human studies with surgical tooth extrusion or synonyms in titles or abstracts were included. A bibliographic analysis, co-occurrence analysis, and coupling of publications were performed. The analysis of variance was used to assess the characteristics of the subgroups based on indications. The survival rate was evaluated by using the Kaplan-Meier method in the R software program (α=.05). RESULTS: Fifty-one studies from 1982 to 2023 were included. The Journal of Dental Traumatology and the Journal of Prosthetic Dentistry combined published approximately one-third of the papers and acquired the most citations. The burst detection of keywords revealed 4 popular research topics: the Benex extraction system, chlorhexidine for infection control, rigid or semi-rigid splints to decrease the risk of complications, and novel restorative materials to improve esthetics. An overall survival rate of 96.36% was reported among 316 participants with 330 extruded teeth. No significant differences were found in study types, geographic distribution, year of publication, or citation counts among the 4 subgroups (surgical extrusion for subgingival fractures, extensive caries, intruded teeth, and unerupted teeth). A significant difference was observed among the Kaplan-Meier curves of the 4 subgroups (P=.030). CONCLUSIONS: Surgical extrusion may be used to save otherwise nonrestorable teeth, and the procedure has shown promising survival rates when teeth are properly selected and the procedure is well executed. Subgingival fractures and extensive caries near bone level are the predominant indications, as well as intruded and unerupted teeth. Surgical extrusion is a reliable treatment option to facilitate tooth restoration for severely damaged teeth, especially for maxillary anterior teeth.

Conservative endodontic microsurgery to protect critical anatomical structures-selective curettage: a case series.

BACKGROUND: Endodontic microsurgery has yielded highly successful outcomes in preserving teeth with persistent or recurrent cases of periapical periodontitis that could not be successfully treated by nonsurgical endodontic approaches. To avoid complications in conditions in which periapical lesions invade anatomical structures such as the nasopalatine nerve tube and mandibular canal, selective curettage has been proposed as an alternative choice of complete curettage in surgery. CASE PRESENTATION: The 8 cases reported herein had undergone root canal treatment and/or retreatment but still presented with symptoms, such as recurring sinus tracts and persistent dull pain. The radiographic examination indicated a large area of radiolucency that was associated with the tooth and had invaded adjacent critical anatomical structures. The patients opted for selective curettage via endodontic microsurgery, and the lesions were histologically confirmed as periapical cysts or granulomas. The follow-up results for one year or more indicated that the affected teeth were clinically asymptomatic and exhibited complete or incomplete healing radiographically. CONCLUSION: This case series provides clinical evidence for the feasibility of selective curettage in endodontic microsurgery, which can avoid complications caused by damage to the adjacent critical anatomical structures.

Prevalence and characteristics of needlestick injuries among dental interns during their first-year clinical training: an observational study.

BACKGROUND: Dental interns are vulnerable to needlestick injuries (NSI). The objectives of this study were to examine the prevalence and characteristics of NSI exposures among dental interns during their first-year clinical training, assess risk factors, and evaluate reporting behaviours. METHODS: An online survey was conducted among dental interns of Class 2011-2017 at Peking University School and Hospital of Stomatology (PKUSS), China. The self-administrated questionnaire consisted of information on demographic profiles, NSI characteristics, and reporting practices. The outcomes were presented by descriptive statistics. A multivariate regression analysis was performed to assess NSI sources using a forward step-wise approach. RESULTS: A total of 407 dental interns completed the survey (response rate 91.9%, 407/443), and 23.8% sustained at least one NSI. The mean number of NSIs per intern was 0.28 during the first clinical year. More occupation exposures occurred from October to December, between 13:00-15:00. Syringe needles were the most frequent sources, followed by dental burs, suture needles, and ultrasonic chips. The risk of peer-inflicted NSIs in the department of Paediatric Dentistry was 12.1 times higher than that in Oral Surgery (OR 12.1, 95% CI: 1.4-101.4). Appropriately 64.9% NSIs occurred when chairside assistants were absent. Compared to working alone, the risk of peer-inflicted NSIs was 32.3 times higher when providing chairside assistance (OR 32.3, 95% CI: 7.2-145.4). The left-hand index finger was the most commonly injured site. About 71.4% of exposures were reported in paperwork. CONCLUSIONS: Dental interns are susceptible to NSIs during their first-year clinical training. Extra attention should be paid to syringe needles, dental burs, suture needles, and ultrasonic chips. The lack of chairside assistance is hazardous regarding NSIs. The training of chairside assistance of the first-year dental interns should be enhanced. First-year dental interns are required to increase their awareness of ignored behaviors related to NSI exposures.

OUTCOMES OF AUTOTRANSPLANTED THIRD MOLARS WITH COMPLETE ROOT FORMATION: A SYSTEMIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Clear evidence is lacking regarding the outcomes of autogenous tooth transplantation (ATT) of third molars with complete root formation. The current review aims to explore the long-term survival and complication rates. METHODS: A comprehensive search was performed in December 2022 of the PubMed, Scopus, Embase, EBSCO, Ovid, Science Direct, and Web of Science databases. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered at the International Prospective Register of Systematic Reviews (CRD42022337659). The pooled survival, root resorption, and ankyloses rates were calculated. Subgroup analyses were performed to explore the effects of sample size and 3D techniques. RESULTS: Twelve studies from 5 countries fulfilled the eligibility, with 759 third molars transplanted in 723 patients. Five studies reported 100% survival at 1-year follow-up. After excluding these 5 studies, the pooled survival rate was 93.62% at 1 year. The survival rate of 1 large sample study was significantly higher than that of small ones at 5 years. The complications of studies using 3D techniques were: root resorption 2.06% (95% CI: 0.22, 7.50) and ankyloses 2.81% (95% CI: 0.16, 12.22), compared to those without 3D techniques: root resorption 10.18% (95% CI: 4.50, 17.80) and ankyloses 6.49% (95% CI: 3.45, 10.96). CONCLUSIONS: ATT of third molars with complete root formation is a reliable alternative for replacement of a missing tooth and has a promising survival rate. The use of 3D techniques can reduce complication rates and improve long-term survival.

MtTRC-1, a Novel Transcription Factor, Regulates Cellulase Production via Directly Modulating the Genes Expression of the Mthac-1 and Mtcbh-1 in Myceliophthora thermophila.

The thermophilic fungus Myceliophthora thermophila has been used to produce industrial enzymes and biobased chemicals. In saprotrophic fungi, the mechanisms regulating cellulase production have been studied, which revealed the involvement of multiple transcription factors. However, in M. thermophila, the transcription factors influencing cellulase gene expression and secretion remain largely unknown. In this study, we identified and characterized a novel cellulase regulator (MtTRC-1) in M. thermophila through a combination of functional genomics and genetic analyses. Deletion of Mttrc-1 resulted in significantly decreased cellulase production and activities. Transcriptome analysis revealed downregulation of not only the encoding genes of main cellulases but also the transcriptional regulator MtHAC-1 of UPR pathway after disruption of MtTRC-1 under cellulolytic induction conditions. Herein, we also characterized the ortholog of the yeast HAC1p in M. thermophila. We show that Mthac-1 mRNA undergoes an endoplasmic reticulum (ER) stress-induced splicing by removing a 23-nucleotide (nt) intron. Notably, the protein secretion on cellulose was dramatically impaired by the deletion of MtHAC-1. Moreover, the colonial growth on various carbon sources was defective in the absence of MtHAC-1. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays verified MtTRC-1 regulates the transcription of Mthac-1 and the major cellulase gene Mtcbh-1 by binding directly to the promoters in vitro and in vivo. Furthermore, DNase I footprinting assays identified the putative consensus binding site (5'-GNG/C-3'). These results revealed the importance of MtTRC-1 for positively regulating cellulase production. This finding has clarified the complex regulatory pathways involved in cellulolytic enzyme production. IMPORTANCE In the present study, we characterized a novel regulator MtTRC-1 in M. thermophila, which regulated cellulase production through direct transcriptional regulation of the Mthac-1 and Mtcbh-1 genes. Our data demonstrated that MtHAC-1 is a key factor for the cellulase secretion capacity of M. thermophila. Our data indicate that this thermophilic fungus regulates cellulase production through a multilevels network, in which the protein secretory pathway is modulated by MtHAC-1-dependent UPR pathway and the cellulase gene expression is directly regulated in parallel by transcription factors. The conservation of Mttrc1 in filamentous fungi suggests this mechanism may be exploited to engineer filamentous fungal cell factories capable of producing proteins on an industrial scale.

Optimization and Characterization of Low-Molecular-Weight Chitosan-Coated Baicalin mPEG-PLGA Nanoparticles for the Treatment of Cataract.

The present study was to evaluate the potential effectiveness of low-molecular-weight chitosan-coated baicalin methoxy poly(ethylene glycol)-poly(d,l-lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (BA LCH NPs) for the treatment of cataract. mPEG-PLGA NPs were optimized by the Box-Behnken design and the central composite design based on the encapsulation efficiency and drug loading. Then, the BA LCH NPs were characterized based on morphology, particle size, and zeta potentials. The analytical data of differential scanning calorimetry, X-ray diffraction, and transmission electron microscopy depicted the drug excipient compatibility. In vitro, we evaluated cell viability, cellular uptake, potential ocular irritation, transcorneal permeability, and the precorneal retention of BA LCH NPs. In vivo, the chronic selenium cataract model was selected to assess the therapeutic effect of BA LCH NPs. The size of BA LCH NPs was within the range from 148 to 219 nm and the zeta potential was 19-25 mV. Cellular uptake results showed that the fluorescence intensity of the preparations in each group increased with time, and the fluorescence intensity of the LCH NP group was significantly higher than that of the solution group. The optimized BA LCH NPs improved precorneal residence time without causing eye irritation and also showed a sustained release of BA through the cornea for effective management of cataract. Also, fluorescence tracking on the rabbit cornea showed increased corneal retention of the LCH NPs. In addition, the results of therapeutic efficacy demonstrated that BA LCH NPs can significantly reduce the content of malondialdehyde and enhanced the activities of catalase, superoxide dismutase, and glutathione peroxidase, which was comparable to positive control and better than the BA solution group. Thus, it can be inferred that the BA LCH NPs are a promising drug delivery system for enhancing the ophthalmic administration of BA to the posterior segment of the eye and improving cataract symptoms.

Genetic origin of patients having spastic paraplegia with or without other neurologic manifestations.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases characterized by lower-limb spastic paraplegia with highly genetic and clinical heterogeneity. However, the clinical sign of spastic paraplegia can also be seen in a variety of hereditary neurologic diseases with bilateral corticospinal tract impairment. The purpose of this study is to identify the disease spectrum of spastic paraplegia, and to broaden the coverage of genetic testing and recognize clinical, laboratorial, electrophysiological and radiological characteristics to increase the positive rate of diagnosis. METHODS: Twenty-seven cases were screened out to have definite or suspected pathogenic variants from clinically suspected HSP pedigrees through HSP-associated sequencing and/or expanded genetic testing. One case was performed for enzyme detection of leukodystrophy without next-generation sequencing. In addition, detailed clinical, laboratorial, electrophysiological and radiological characteristics of the 28 patients were presented. RESULTS: A total of five types of hereditary neurological disorders were identified in 28 patients, including HSP (15/28), leukodystrophy (5/28), hereditary ataxia (2/28), methylmalonic acidemia/methylenetetrahydrofolate reductase deficiency (5/28), and Charcot-Marie-tooth atrophy (1/28). Patients in the HSP group had chronic courses, most of whom were lower limbs spasticity, mainly with axonal neuropathy, and thinning corpus callosum, white matter lesions and cerebellar atrophy in brain MRI. In the non-HSP groups, upper and lower limbs both involvement was more common. Patients with homocysteine remethylation disorders or Krabbe's disease or autosomal recessive spastic ataxia of Charlevoix-Saguenay had diagnostic results in laboratory or imaging examination. A total of 12 new variants were obtained. CONCLUSIONS: HSP had widespread clinical and genetic heterogeneity, and leukodystrophy, hereditary ataxia, Charcot-Marie-Tooth atrophy and homocysteine remethylation disorders accounted for a significant proportion of the proposed HSP. These diseases had different characteristics in clinical, laboratorial, electrophysiological, and radiological aspects, which could help differential diagnosis. Genetic analysis could ultimately provide a clear diagnosis, and broadening the scope of genetic testing could improve the positive rate of diagnosis.

Macrophage membrane modified baicalin liposomes improve brain targeting for alleviating cerebral ischemia reperfusion injury.

Baicalin (BA) has a good intervention effect on encephalopathy. In this study, macrophage membrane was modified on the surface of baicalin liposomes (BA-LP) by extrusion method. Macrophage membrane modified BA-LP (MM-BA-LP) was characterized by various analytical techniques, and evaluated for brain targeting. The results presented MM-BA-LP had better brain targeting compared with BA-LP. Pharmacokinetic experiments showed that MM-BA-LP improved pharmacokinetic parameters and increased the residence time of BA. Pharmacodynamic of middle cerebral artery occlusion (MCAO) rat model was studied to verify the therapeutic effect of MM-BA-LP on cerebral ischemia reperfusion injury (CIRI). The results showed that MM-BA-LP could significantly improve the neurological deficit, cerebral infarction volume and brain pathological state of MCAO rats compared with BA-LP. These results suggested that MM-BA-LP could significantly enhance the brain targeting and improve the circulation of BA in blood, and had a significantly better neuroprotective effect on MCAO rats than BA-LP.

Atomic-level engineering and imaging of polypeptoid crystal lattices.

Rational design of supramolecular nanomaterials fundamentally depends upon an atomic-level understanding of their structure and how it responds to chemical modifications. Here we studied a series of crystalline diblock copolypeptoids by a combination of sequence-controlled synthesis, cryogenic transmission electron microscopy, and molecular dynamics simulation. This family of amphiphilic polypeptoids formed free-floating 2-dimensional monolayer nanosheets, in which individual polymer chains and their relative orientations could be directly observed. Furthermore, bromine atom side-chain substituents in nanosheets were directly visualized by cryogenic transmission electron microscopy, revealing atomic details in position space inaccessible by conventional scattering techniques. While the polypeptoid backbone conformation was conserved across the set of molecules, the nanosheets exhibited different lattice packing geometries dependent on the aromatic side chain para substitutions. Peptoids are inherently achiral, yet we showed that sequences containing an asymmetric aromatic substitution pattern pack with alternating rows adopting opposite backbone chiralities. These atomic-level insights into peptoid nanosheet crystal structure provide guidance for the future design of bioinspired nanomaterials with more precisely controlled structures and properties.

Effect and Mechanism of Pharmaceutical Excipients on Berberine to Alleviate Ulcerative Colitis via Regulating Gut Microbiota.

BACKGROUND: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. METHODS: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. RESULTS: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1ß, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. CONCLUSIONS: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs' therapeutic efficiency outcome.

Penehyclidine for prevention of postoperative nausea and vomiting following bimaxillary orthognathic surgery: a randomized, double-blind, controlled trial.

PURPOSE: To investigate the efficacy and safety of low-dose bolus plus continuous infusion of penehyclidine in preventing postoperative nausea and vomiting (PONV) following bimaxillary surgery. METHODS: Three hundred fifty-four patients were randomly allocated into three groups. In the Control group, placebo (normal saline) was injected before anesthesia and infused over 48 h after surgery; in the Bolus group, 0.5 mg penehyclidine was injected before anesthesia, whereas placebo was infused after surgery; in the Infusion group, 0.25 mg penehyclidine were injected before anesthesia, another 0.25 mg penehyclidine was infused after surgery. The primary endpoint was the incidence of PONV within 72 h. RESULTS: A total of 353 patients were included in intention-to-treat analysis. The PONV incidence was 61.0% (72/118) in the Control group, 40.2% (47/117) in the Bolus group, and 28.0% (33/118) in the Infusion group. The incidence was significantly lower in the Bolus group than in the Control group (RR 0.66; 95% CI 0.51-0.86; adjusted P = 0.003) and in the Infusion group than in the Control group (RR 0.46; 95% CI 0.33-0.63; adjusted P < 0.001); the difference between the Infusion and Bolus groups was not statistically significant (RR 0.70; 95% CI 0.48-1.00; adjusted P = 0.144). Emergence agitation occurred more frequently in the Bolus group than in the Control group (36.8% [43/117] vs. 21.2% [25/118], adjusted P = 0.027), but did not differ significantly between the Infusion and Control groups. CONCLUSIONS: A low-dose bolus plus continuous infusion of penehyclidine was effective in preventing PONV without increasing emergence agitation. TRIAL REGISTRATION: Clinicaltrials.gov. Identifier: NCT04454866.