A spike-based mRNA vaccine that induces durable and broad protection against porcine deltacoronavirus in piglets.

Coronaviruses (CoVs) are important pathogens for humans and other vertebrates, causing severe respiratory and intestinal infections that have become a threat to public health because of the potential for interspecies transmission between animals and humans. Therefore, the development of safe, effective vaccines remains a top priority for the control of CoV infection. The unique immunological characteristics of vaccines featuring messenger RNA (mRNA) present an advantageous tool for coronavirus vaccine development. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines: one encoding full-length spike (S) protein and the other encoding the spike ectodomain (Se) from porcine deltacoronavirus (PDCoV). Fourteen days after primary immunization, both mRNA vaccines induced high levels of immunoglobulin G and neutralizing antibodies in mice, with the S vaccine showing better performance than the Se vaccine. Passive immune protection of the S mRNA vaccine in suckling piglets was confirmed by the induction of robust PDCoV-specific humoral and cellular immune responses. The S mRNA vaccine also showed better protective effects than the inactivated vaccine. Our results suggest that the novel PDCoV-S mRNA-LNP vaccine may have the potential to combat PDCoV infection. IMPORTANCE: As an emerging porcine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) has the potential for cross-species transmission, attracting extensive attention. Messenger RNA (mRNA) vaccines are a promising option for combating emerging and re-emerging infectious diseases, as evidenced by the demonstrated efficacy of the COVID-19 mRNA vaccine. Here, we first demonstrated that PDCoV-S mRNA-lipid nanoparticle (LNP) vaccines could induce potent humoral and cellular immune responses in mice. An evaluation of passive immune protection of S mRNA vaccines in suckling piglets confirmed that the protective effect of mRNA vaccine was better than that of inactivated vaccine. This study suggests that the PDCoV-S mRNA-LNP vaccine may serve as a potential and novel vaccine candidate for combating PDCoV infection.

Enamel proteome shows that Gigantopithecus was an early diverging pongine.

Gigantopithecus blacki was a giant hominid that inhabited densely forested environments of Southeast Asia during the Pleistocene epoch1. Its evolutionary relationships to other great ape species, and the divergence of these species during the Middle and Late Miocene epoch (16-5.3 million years ago), remain unclear2,3. Hypotheses regarding the relationships between Gigantopithecus and extinct and extant hominids are wide ranging but difficult to substantiate because of its highly derived dentognathic morphology, the absence of cranial and post-cranial remains1,3-6, and the lack of independent molecular validation. We retrieved dental enamel proteome sequences from a 1.9-million-year-old G. blacki molar found in Chuifeng Cave, China7,8. The thermal age of these protein sequences is approximately five times greater than that of any previously published mammalian proteome or genome. We demonstrate that Gigantopithecus is a sister clade to orangutans (genus Pongo) with a common ancestor about 12-10 million years ago, implying that the divergence of Gigantopithecus from Pongo forms part of the Miocene radiation of great apes. In addition, we hypothesize that the expression of alpha-2-HS-glycoprotein, which has not been previously observed in enamel proteomes, had a role in the biomineralization of the thick enamel crowns that characterize the large molars in Gigantopithecus9,10. The survival of an Early Pleistocene dental enamel proteome in the subtropics further expands the scope of palaeoproteomic analysis into geographical areas and time periods previously considered incompatible with the preservation of substantial amounts of genetic information.

Chemoimmunotherapeutic Nanogel for Pre- and Postsurgical Treatment of Malignant Melanoma by Reprogramming Tumor-Associated Macrophages.

Surgery is the primary method to treat malignant melanoma; however, the residual microtumors that cannot be resected completely often trigger tumor recurrence, causing tumor-related mortality following melanoma resection. Herein, we developed a feasible strategy based on the combinational chemoimmunotherapy by cross-linking carboxymethyl chitosan (CMCS)-originated polymetformin (PolyMetCMCS) with cystamine to prepare stimuli-responsive nanogel (PMNG) owing to the disulfide bond in cystamine that can be cleaved by the massive glutathione (GSH) in tumor sites. Then, chemotherapeutic agent doxorubicin (DOX) was loaded in PMNG, which was followed by a hyaluronic acid coating to improve the overall biocompatibility and targeting ability of the prepared nanogel (D@HPMNG). Notably, PMNG effectively reshaped the tumor immune microenvironment by reprogramming tumor-associated macrophage phenotypes and recruiting intratumoral CD8+ T cells owing to the inherited immunomodulatory capability of metformin. Consequently, D@HPMNG treatment remarkably suppressed melanoma growth and inhibited its recurrence after surgical resection, proposing a promising solution for overcoming lethal melanoma recurrence.

Black Phosphorus Quantum Dot Loaded Bioinspired Nanoplatform Synergized with aPD-L1 for Multimode Cancer Immunotherapy.

Efforts to prolong the blood circulation time and bypass immune clearance play vital roles in improving the therapeutic efficacy of nanoparticles (NPs). Herein, a multifunctional nanoplatform (BPP@RTL) that precisely targets tumor cells is fabricated by encapsulating ultrasmall phototherapeutic agent black phosphorus quantum dot (BPQD), chemotherapeutic drug paclitaxel (PTX), and immunomodulator PolyMetformin (PM) in hybrid membrane-camouflaged liposomes. Specifically, the hybrid cell membrane coating derived from the fusion of cancer cell membrane and red blood cell membrane displays excellent tumor targeting efficiency and long blood circulation property due to the innate features of both membranes. After collaboration with aPD-L1-based immune checkpoint blockade therapy, a boosted immunotherapeutic effect is obtained due to elevated dendritic cell maturation and T cell activation. Significantly, laser-irradiated BPP@RTL combined with aPD-L1 effectively eliminates primary tumors and inhibits lung metastasis in 4T1 breast tumor model, offering a promising treatment plan to develop personalized antitumor strategy.

Evidence for the smallest fossil Pongo in southern China.

The rarity of Pongo fossils with precise absolute dating from the Middle Pleistocene hampers our understanding of the taxonomy and spatiotemporal distribution of Quaternary orangutans in southern China. Here, we report a newly discovered sample of 113 isolated teeth of fossil Pongo from Zhongshan Cave in the Bubing Basin, Guangxi, southern China. We describe the Pongo specimens from Zhongshan Cave and compare them metrically to other samples of fossil Pongo species (i.e., Pongo weidenreichi, Pongo devosi, Pongo duboisi, Pongo palaeosumatrensis, Pongo javensis, and Pongo sp.) and to extant orangutans (i.e., Pongo pygmaeus and Pongo abelii). The Zhongshan Pongo assemblage is dated using U-series and coupled electron spin resonance/U-series methods. Our results reasonably constrain the Zhongshan Pongo assemblage to 184 ± 16 ka, which is consistent with the biostratigraphic evidence. The Zhongshan Pongo teeth are only 6.5% larger on average than those of extant Pongo. The Zhongshan teeth are smaller overall than those of Pongo from all other cave sites in southern China, and they currently represent the smallest fossil orangutans in southern China. Based on their dental size, and the presence of a well-developed lingual pillar and lingual cingulum on the upper and lower incisors, an intermediate frequency of lingual cingulum remnants on the upper molars, and a higher frequency of moderate to heavy wrinkling on the upper and lower molars, we provisionally assign the Zhongshan fossils to P. devosi. Our results confirm earlier claims that P. weidenreichi is replaced by a smaller species in southern China, P. devosi, by the late Middle Pleistocene. The occurrence of P. devosi in Zhongshan Cave further extends its spatial and temporal distribution. The Pongo specimens from Zhongshan provide important new evidence to demonstrate that the dental morphological features of Pongo in southern China changed substantially during the late Middle Pleistocene.

The role of Gel-Ppy-modified nerve conduit on the repair of sciatic nerve defect in rat model.

The serious clinical challenge of peripheral nerve injury (PNI) is nerve regeneration. Nerve conduit represents a promising strategy to contribute to nerve regeneration by bridging injured nerve gaps. However, due to a unique microenvironment of nerve tissue, autologous nerves have not been substituted by nerve conduit. Nerve regeneration after nerve conduit implantation depends on many factors, such as conductivity and biocompatibility. Therefore, Gelatin (Gel) with biocompatibility and polypyrrole (Ppy) with conductivity is highly concerned. In this paper, Gel-Ppy modified nerve conduit was fabricated with great biocompatibility and conductivity to evaluate its properties of enhancing nerve regeneration in vivo and in vitro. The proliferation of Schwann cells on Gel-Ppy modified nerve conduit was remarkably increased. Consistent with in vitro results, the Gel-Ppy nerve conduit could contribute to the regeneration of Schwann cell in vivo. The axon diameters and myelin sheath thickness were also enhanced, resulting in the amelioration of muscle atrophy, nerve conduction, and motor function recovery. To explain this interesting phenomenon, western blot results indicated that the Gel-Ppy conduit facilitated nerve regeneration via upregulating the Rap1 pathway to induce neurite outgrowth. Therefore, the above results demonstrated that Gel-Ppy modified nerve conduit could provide an acceptable microenvironment for nerve regeneration and be popularized as a novel therapeutic strategy of PNI.

Exposure-efficacy and exposure-safety analyses of ropeginterferon alfa-2b treatment in patients with polycythaemia vera.

AIMS: To investigate the exposure-response (E-R) relationship, including exposure-efficacy and exposure-safety, of ropeginterferon alfa-2b treatment in patients with polycythaemia vera (PV). METHODS: Based on the results of the phase II trial A20-202 regarding ropeginterferon alfa-2b in patients with PV, E-R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E-R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa-2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment-related adverse events (TRAEs). RESULTS: A clear relationship between the exposure to ropeginterferon alfa-2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure-JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa-2b and baseline body surface area. Exposure-safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. CONCLUSIONS: Our analyses have shown that patients with PV treated with ropeginterferon alfa-2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250-350-500 µg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa-2b for PV treatment in China.

Construction of GSH-responsive polyethyleneimine-based delivery vector for effective gene transfection.

The rise of gene therapy has solved many diseases that cannot be effectively treated by conventional methods. Gene vectors is very important to protect and deliver the therapeutic genes to the target site. Polyethyleneimine (PEI) modified with mannitol could enhance the gene transfection efficiency reported by our group previously. In order to further control and improve the effective gene release to action site, disulfide bonds were introduced into mannitol-modified PEI to construct new non-viral gene vectors PeiSM. The degrees of mannitol linking with disulfide bonds were screened. Among them, moderate mannitol-modified PEI with disulfide bonds showed the best transfection efficiency, and significantly enhanced long-term systemic transgene expression for 72 hin vivoeven at a single dose administration, and could promote caveolae-mediated uptake through up-regulating the phosphorylation of caveolin-1 and increase the loaded gene release from the nanocomplexes in high glutathione intracellular environment. This functionalized gene delivery system can be used as an potential and safe non-viral nanovector for further gene therapy.

Nanoplastics Detected in Commercial Sea Salt.

People of all ages consume salt every day, but is it really just salt? Plastic nanoparticles [nanoplastics (NPs)] pose an increasing environmental threat and have begun to contaminate everyday salt in consumer goods. Herein, we developed a combined surface enhanced Raman scattering (SERS) and stimulated Raman scattering (SRS) approach that can realize the filtration, enrichment, and detection of NPs in commercial salt. The Au-loaded (50 nm) anodic alumina oxide substrate was used as the SERS substrate to explore the potential types of NP contaminants in salts. SRS was used to conduct imaging and quantify the presence of the NPs. SRS detection was successfully established through standard plastics, and NPs were identified through the match of the hydrocarbon group of the nanoparticles. Simultaneously, the NPs were quantified based on the high spatial resolution and rapid imaging of the SRS imaging platform. NPs in sea salts produced in Asia, Australasia, Europe, and the Atlantic were studied. We estimate that, depending on the location, an average person could be ingesting as many as 6 million NPs per year through the consumption of sea salt alone. The potential health hazards associated with NP ingestion should not be underestimated.

Microbial Necromass, Lignin, and Glycoproteins for Determining and Optimizing Blue Carbon Formation.

Coastal wetlands contribute to the mitigation of climate change through the sequestration of "blue carbon". Microbial necromass, lignin, and glycoproteins (i.e., glomalin-related soil proteins (GRSP)), as important components of soil organic carbon (SOC), are sensitive to environmental change. However, their contributions to blue carbon formation and the underlying factors remain largely unresolved. To address this paucity of knowledge, we investigated their contributions to blue carbon formation along a salinity gradient in coastal marshes. Our results revealed decreasing contributions of microbial necromass and lignin to blue carbon as the salinity increased, while GRSP showed an opposite trend. Using random forest models, we showed that their contributions to SOC were dependent on microbial biomass and resource stoichiometry. In N-limited saline soils, contributions of microbial necromass to SOC decreased due to increased N-acquisition enzyme activity. Decreases in lignin contributions were linked to reduced mineral protection offered by short-range-ordered Fe (FeSRO). Partial least-squares path modeling (PLS-PM) further indicated that GRSP could increase microbial necromass and lignin formation by enhancing mineral protection. Our findings have implications for improving the accumulation of refractory and mineral-bound organic matter in coastal wetlands, considering the current scenario of heightened nutrient discharge and sea-level rise.

Anaerobic membrane bioreactor coupled with polyaluminum chloride for high-strength phenolic wastewater treatment: Robust performance and potential mechanisms.

Anaerobic digestion of phenolic wastewater by anaerobic membrane bioreactor (AnMBR) has revealed increasing attractiveness, but the application of AnMBRs for treating high-strength phenolic wastewater faces challenges related to elevated phenol stress and membrane fouling. In this study, the coupling of AnMBR and polyaluminum chloride (PAC) was developed for efficient treatment of high-strength phenolic wastewater. The system achieved robust removal efficiencies of phenol (99%) and quinoline (98%) at a gradual increase of phenol concentration from 1000 to 5000 mg/L and a constant quinoline concentration of 100 mg/L. The dosing of PAC could effectively control the membrane fouling rate with the transmembrane pressure (TMP) increasing rate as low as 0.17 kPa/d. The robust performances were mainly attributed to the favorable retention of functional microbes through membrane interception, while pulse cross flow buffered against phenol stress and facilitated cake layer removal. Meanwhile, the enriched core functional microbes, such as Syntrophorhabdus, Syntrophus, Mesotoga and Methanolinea, played a crucial role in further reduction of phenol stress. Notably, the significant presence of biomacromolecule degrader, such as Levilinea, contributed to membrane fouling mitigation through extracellular polymer degradation. Moreover, the enlargement of particle size distribution (PSD) by PAC was expected to mitigate membrane fouling. This study provided a promising avenue for sustainable treatment of high-strength phenolic wastewater.

Tumor targeting peptide TMTP1 modified Antigen capture Nano-vaccine combined with chemotherapy and PD-L1 blockade effectively inhibits growth of ovarian cancer.

The mortality of ovarian cancer (OC) has long been the highest among gynecological malignancies. Although OC is considered to be an immunogenic tumor, the effect of immunotherapy is not satisfactory. The immunosuppressive microenvironment is one reason for this, and the absence of recognized effective antigens for vaccines is another. Chemotherapy, as one of the most commonly used treatment for OC, can produce chemotherapy-associated antigens (CAAs) during treatment and show the effect of in situ vaccine. Herein, we designed an antigen capture nano-vaccine NP-TP1@M-M with tumor targeting peptide TMTP1 and dendritic cell (DC) receptor mannose assembled on the surface and adjuvant monophosphoryl lipid A (MPLA) encapsulated in the core of poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA itself possessed the ability of antigen capture. TMTP1 was a tumor-homing peptide screened by our research team, which held extensive and excellent tumor targeting ability. After these modifications, NP-TP1@M-M could capture and enrich more tumor-specific antigens after chemotherapy, stimulate DC maturation, activate the adaptive immunity and combined with immune checkpoint blockade to maximize the release of the body's immune potential, providing an eutherapeutic strategy for the treatment of OC.

Engineering hydrogels with homogeneous mechanical properties for controlling stem cell lineage specification.

The extracellular matrix (ECM) is mechanically inhomogeneous due to the presence of a wide spectrum of biomacromolecules and hierarchically assembled structures at the nanoscale. Mechanical inhomogeneity can be even more pronounced under pathological conditions due to injury, fibrogenesis, or tumorigenesis. Although considerable progress has been devoted to engineering synthetic hydrogels to mimic the ECM, the effect of the mechanical inhomogeneity of hydrogels has been widely overlooked. Here, we develop a method based on host-guest chemistry to control the homogeneity of maleimide-thiol cross-linked poly(ethylene glycol) hydrogels. We show that mechanical homogeneity plays an important role in controlling the differentiation or stemness maintenance of human embryonic stem cells. Inhomogeneous hydrogels disrupt actin assembly and lead to reduced YAP activation levels, while homogeneous hydrogels promote mechanotransduction. Thus, the method we developed to minimize the mechanical inhomogeneity of hydrogels may have broad applications in cell culture and tissue engineering.

Ancient DNA and multimethod dating confirm the late arrival of anatomically modern humans in southern China.

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

Clinical Research on Rett Syndrome: Central Hypoxemia and Hypokalemic Metabolic Alkalosis.

Background: Rett syndrome (RTT) is now widely recognized as a profound neurological disorder that predominantly affects females and is closely associated with mutations in the methylated CpG binding protein 2 (MECP2) gene located on the X chromosome. The Characteristic symptoms of RTT include the loss of acquired language and motor skills, repetitive hand movements, irregular breathing, and seizures. Additionally, RTT patients may experience sporadic episodes of gastrointestinal problems, hypoplasia, early-onset osteoporosis, bruxism, and screaming episodes. It is worth noting that males exhibit a unique and variable phenotype, though rare in RTT cases, often accompanied by severe manifestations. Case Presentation: In this report, we present the case of a young male child with a de novo c.806delG hemizygous mutation, leading to an atypical presentation of RTT that remarkably mirrors the clinical features of Bartter syndrome, a genetic metabolic disorder. The clinical manifestations in this case included the loss of previously acquired language and motor skills, repetitive hand movements, breathing irregularities, seizures, sporadic episodes of gastrointestinal distress, hypoplasia, early-onset osteoporosis, bruxism, and episodes of screaming. This distinctive presentation underscores the complex diagnostic landscape of RTT, particularly in males, and highlights the need for vigilant clinical evaluation. Conclusions: This case report sheds light on an unusual and atypical presentation of RTT in a young male child with a de novo c.806delG hemizygous mutation. The resemblance of clinical features to Bartter syndrome underscores the diagnostic challenges posed by RTT and highlights the importance of comprehensive clinical assessment and genetic testing, especially in cases deviating from the typical RTT phenotype. Our findings contribute valuable insights into the early diagnosis and management of atypical RTT presentations.

Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

Improving physicochemical characteristics and cytotoxicity of baicalin esters by liposome encapsulation.

The instability of ester bonds, low water solubility, and increased cytotoxicity of flavonoid glycoside esters significantly limit their application in the food industry. Therefore, the present study attempted to resolve these issues through liposome encapsulation. The results showed that baicalin butyl ester (BEC4) and octyl ester (BEC8) have higher encapsulation and loading efficiencies and lower leakage rate from liposomes than baicalin. FTIR results revealed the location of BEC4 and BEC8 in the hydrophobic layer of liposomes, which was different from baicalin. Additionally, liposome encapsulation improved the water solubility and stability of BEC4 and BEC8 in the digestive system and PBS but significantly reduced their cytotoxicity. Furthermore, the release rate of BEC4 and BEC8 from liposomes was lower than that of baicalin during gastrointestinal digestion. These results indicate that liposome encapsulation alleviated the negative effects of fatty chain introduction into flavonoid glycosides.

Effects of different patterns of movement for correcting a deep curve of Spee with clear aligners on the anterior teeth: a finite element analysis.

OBJECTIVE: To analyse the anterior teeth effects of clear aligners on five different patterns of mandibular molar movement and to define the most effective configuration to be implemented with clear aligners through finite element analysis. METHODS: A three-dimensional mandibular model with a deep overbite in the mandible was constructed using cone beam computerized tomography (CBCT) data. The model included the mandibular dentition, mandibular periodontal ligaments, attachments, and aligners. Five models were created: (1) configuration A: second molar distalization (0.25 mm); (2) configuration B: second molar distalization (0.25 mm), first molar extrusion (0.15 mm); (3) configuration C: second molar distalization (0.25 mmm), first and second premolar extrusion(0.15 mm); (4) configuration D: second molar distalization (0.25 mm), first molar and first/second premolar extrusion(0.15 mm); and (5) configuration E: second molar distalization (0.25 mm), first molar and first/second premolar extrusion (0.15 mm), first molar and first/second premolar expansion (0.15 mm). RESULTS: In all configurations, the anterior teeth exhibited labial tipping and the mandibular central incisor of configuration E showed the highest labial tipping. Configuration E demonstrated a relatively minor impact on mandibular molars distalization compared with configuration A. Configuration A showed the highest distal displacement value, and configuration E produced the lowest displacement value. Configuration E caused the highest periodontal ligament (PDL) pressure of the central and lateral incisors. The differences in the canines between configurations C and D,were not significant, and the stress distribution differed among the five groups. CONCLUSIONS: All patterns utilizing clear aligners facilitated mandibular molar distalization. Extruding the premolars and second molar distalization at the same time had little impact on second molar distalization; When expansion and extrusion were simultaneously performed during the distalization of mandibular molars, our prime consideration was the alveolar bone on the labial side of the anterior teeth to prevent the occurrence of gingival recession, dehiscence, and fenestration. Due to the lack of consideration for periodontal tissues in this study, clinical protocols should be designed based on the periodontal status of the mandibular anterior teeth.

Anchorage loss of the posterior teeth under different extraction patterns in maxillary and mandibular arches using clear aligner: a finite element study.

BACKGROUND: Extracting the premolars is an effective strategy for patients with bimaxillary dentoalveolar protrusion. Clear aligners (CAs) close the extraction spaces through shortening the length of aligners. The contraction force generated by the terminal of aligners makes the posterior teeth tip mesially, which is known as the roller coaster effect. This phenomenon is even worse in the 2nd premolar extraction cases. Posterior anchorage preparation is commonly used to protect the angulation of molars, taking the form of presetting distal tipping value. However, the distal tipping design aggravates the anchorage loss of anterior teeth simultaneously. This study aimed to explore the different anchorage loss of the posterior teeth when the 1st or 2nd premolars were extracted using CAs, respectively in maxillary and mandibular arches, further providing guidance for anchorage preparation design in clinical practice. METHODS: Two bimaxillary finite element models with different extraction patterns were established to simulate the anterior en-masse retraction process of the CAs. In Model 1, the maxillary and mandibular 1st premolars were extracted, while in Model 2, the 2nd premolars were extracted. Finite element analysis methods were utilized to analyze the tipping angle of the anterior and posterior teeth. RESULTS: Compared between two models, the anterior teeth exhibited a greater lingual inclination tendency and the posterior teeth exhibited a slighter mesial tipping tendency in Model 1 regarding individual tooth. The closer to the extraction spaces, the greater the tip, and the distal tipping tendency of the 1st premolars was more evident than the mesial tipping tendency of the 1st molars in Model 2. Compared between the maxillary and mandibular arches, the mesial tipping tendency of individual posterior tooth was more evident in the maxilla. In addition, the highest hydrostatic stress of the periodontal ligaments was concentrated on the cervical and apical parts directly adjacent to the extraction spaces, and it exhibited relatively uniform distribution in Model 1. CONCLUSIONS: The individual posterior tooth showed the same mesial tipping direction but to different degree when the 1st or the 2nd premolars were extracted during clear aligner treatment. Presetting anchorage preparation design for the posterior teeth is essential to alleviate the roller coaster effect, especially in the 2nd premolar extraction cases. Furthermore, larger anchorage preparation value should be proposed for the maxillary posterior teeth.

The influence of direct anterior approach and postero-lateral approach on wound complications after total hip arthroplasty: A meta-analysis.

To date, we have reviewed the synthesis literature critically through four databases: PubMed, Embase, Cochrane Library and Web of Science. Eight relevant studies were examined after compliance with the criteria for inclusion and exclusion, as well as documentation quality evaluation. This report covered all randomised, controlled studies of total hip arthroplasty (THA) comparing the direct anterior approach (DAA) with the postero-lateral approach (PLA). The main result was surgical site infection rate. The secondary results were duration of the operation, length of the incision and VAS score after surgery. The results of the meta-analyses of wound infections in the present trial did not show any statistically significant difference in DAA versus PLA (between DAA and PLA) (OR = 1.42, 95%CI: 0.5 to 4.04, p = 0.51). Compared with PLA, DAA had shorter surgical incision (WMD = -3.2, 95%CI: -4.00 to -2.41; p < 0.001) and longer operative times(WMD = 14. 67, 95%CI: 9.24 to 20.09; p < 0.001). Postoperative VAS scores were markedly lower in DAA compared with PLA within 6 weeks of surgery (p < 0.05), with low heterogeneities(I2 = 0). We found that DAA did not differ significantly from PLA in terms of the risk of wound infection for THA and that the surgical incisions was shorter and less postoperative pain after surgery, even though DAA surgery takes longer.