Molecular Epidemiology of Human Norovirus Variants from Outbreaks in Zhejiang Province, China, during 2021.

Background: Noroviruses are the most frequent cause of epidemic acute viral gastroenteritis in China. Objectives: The aim of this study was to determine the molecular epidemiological characteristics of norovirus outbreaks and the molecular genetic features of norovirus in Zhejiang Province during 2021. Methods: First, the local Centers for Disease Control and Prevention in the outbreak area conducted on-site epidemiologic investigations and collected samples from ill patients for initial testing. The general epidemiologic characteristics of the demographic information are presented through descriptive analysis. Positive samples were sent to the Microbiology Laboratory of Zhejiang Provincial Center for Disease Control and Prevention for further verification. The presence of norovirus genogroups I (GI) and II (GII), along with sapovirus, was detected. Subsequently, the specimens positive for norovirus were sequenced for genotyping purposes. Furthermore, the whole genomes of positive samples were sequenced, enabling the characterization of both nucleotide and amino acid differences within the virus. Finally, phylogenetic trees were constructed to further analyze and understand the genetic relationships among the detected viruses. Result: 227 norovirus outbreaks were reported in Zhejiang Province, China, during 2021. Schools were the main setting while January was the peak month for outbreaks. A total of 17 diverse genotypes of norovirus were identified in 2021, and GII.P16-GII.2 was the most frequent genotype (30.19%). Seven genomes (five GI.P4-GI.5 and two GII.P16-GII.2) were obtained. Although GI.P4-GI.5 is considered to be a rare genotype of norovirus, the prevalence might have been underestimated. Capsid microvariation of GII.2 displayed histo-blood group antigen binding patterns compared to the GII.2 prototype, although VP1 sequences were considered to have a minimal impact on antigenicity. Conclusion: This study revealed the diversity of norovirus strains' genotypes circulating in Zhejiang Province in 2021. Continued molecular surveillance of noroviruses should be strengthened in our further efforts to the development of vaccines.

First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial.

Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

Circumventing bottlenecks in H2O2 photosynthesis over carbon nitride with iodine redox chemistry and electric field effects.

Artificial photosynthesis using carbon nitride (g-C3N4) holds a great promise for sustainable and cost-effective H2O2 production, but the high carrier recombination rate impedes its efficiency. To tackle this challenge, we propose an innovative method involving multispecies iodine mediators (I-/I3-) intercalation through a pre-photo-oxidation process using potassium iodide (suspected deteriorated "KI") within the g-C3N4 framework. Moreover, we introduce an external electric field by incorporating cationic methyl viologen ions to establish an auxiliary electron transfer channel. Such a unique design drastically improves the separation of photo-generated carriers, achieving an impressive H2O2 production rate of 46.40 mmol g-1 h-1 under visible light irradiation, surpassing the most visible-light H2O2-producing systems. Combining various advanced characterization techniques elucidates the inner photocatalytic mechanism, and the application potential of this photocatalytic system is validated with various simulation scenarios. This work presents a significative strategy for preparing and applying highly efficient g-C3N4-based catalysts in photochemical H2O2 production.

Custom-Designed Probes for the Accurate Determination of Epidermal Growth Factor Receptor Mutations and Their Allelic Configuration.

The identification of single nucleotide polymorphisms (SNPs) is of paramount importance for disease diagnosis and clinical prognostication. In the context of nonsmall cell lung cancer (NSCLC), the emergence of resistance mutations, exemplified by the epidermal growth factor receptor (EGFR) T790 M and C797S, is intricately linked to the therapeutic efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Herein, a highly efficient and specific SNP detection platform for T790 M and C797S mutations has been engineered through the integration of an asymmetric polymerase chain reaction (PCR) and an ingeniously tailored four-way junction (4WJ) probe. Notably, a molecular beacon (MB) probe was judiciously designed to discern the allelic configuration of these mutations. The administration of first- and third-generation EGFR-TKIs demonstrates therapeutic efficacy solely when the mutations are in the trans configuration, characterized by a low fluorescence signal. In contrast, significant fluorescence by the MB probe is indicative of the C797S mutation being in a cis arrangement with T790M, thereby rendering the cells refractory to the therapeutic interventions of both first- and third-generation EGFR-TKIs. The assay is capable of concurrently detecting two point-mutations and ascertaining their allelic positions in a single test within 1.5 h, enhancing both efficiency and simplicity. It also exhibits high accuracy in the identification of clinical samples, offering promising implications for therapeutic guidelines. By enabling tailored treatment plans based on specific genetic profiles, our approach not only advances the precision of NSCLC treatment strategies but also marks a significant contribution to personalized medicine.

Phosphorylation of LSD1 at serine 54 regulates genes involved in follicle selection by enhancing demethylation activity in chicken ovarian granulosa cells.

Follicle selection in chicken refers to the process of selecting a follicle to enter hierarchy from a cohort of small yellow follicles (SY) with a diameter of 6 to 8 mm. The follicle being selected will develop rapidly and ovulate. Follicle selection is a key stage affecting chicken egg-laying performance. Our previous study showed that the phosphorylation level of lysine (K)-specific demethylase 1A (LSD1) at serine 54 (LSD1Ser54p) was significantly increased in F6 follicles compared to prehierarchal SY follicles, but its function was unclear. Here, the mechanism of this modification, the effect of LSD1Ser54p dephosphorylation on gene expression profile of chicken hierarchal granulosa cells and the function of fibroblast growth factor 9 (FGF9) that is regulated by LSD1Ser54p were further investigated. The modification of LSD1Ser54p was predicted to be mediated by cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3 (GSK3). Treatment of chicken hierarchal granulosa cells with CDK5 inhibitor significantly decreased LSD1Ser54p level (P < 0.05) and LSD1Ser54p interacted with CDK5, suggesting that, in the granulosa cells of chicken hierarchal follicles, LSD1Ser54p modification was carried out by CDK5. When the LSD1Ser54p level decreased in the granulosa cells of chicken hierarchal follicles, both the mRNA expression of FGF9 and α-actinin 2 (ACTN2) and the H3K4me2 level in their promoter regions significantly increased (P < 0.05), indicating that this phosphorylation modification enhanced the demethylation activity of LSD1. Moreover, in chicken hierarchal granulosa cells, overexpression of chicken FGF9 stimulated their proliferation and increased the mRNA expression of hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (Hsd3b) and steroidogenic acute regulatory protein (StAR). This study collectively revealed that phosphorylation of LSD1 at serine 54 by CDK5 enhanced its demethylation activity in chicken ovarian granulosa cells and regulated genes including FGF9 that is engaged in chicken follicle selection.

Synthesis of micro-crosslinked adamantane-containing matrix resins designed for deep-UV lithography resists and their application in nanoimprint lithography.

A certain type of photoresist used for deep-UV lithography (DUVL) can also be used for other types of photolithography. Thus, to meet the requirements of two or more lithography technologies simultaneously, it is necessary to design a variety of corresponding functional groups in the molecules of materials and obtain the required properties. Herein, we designed four matrix resins based on acrylate for DUVL, employing alkyl sulfide, adamantane, methyladamantane, and hydroxyl as dangling groups and a microcrosslinking network by adding a small amount of crosslinker. These polymers were used in the thermal nanoimprint lithography (NIL) process, and distinct patterns with a resolution of 100 nm were observed. The acrylate copolymers designed for DUVL in this work can be used as thermal NIL resists and to obtain good patterns. It was found that ethylene dimethacrylate (EDMA) and adamantane endowed the matrix resins with good thermal stability and that PMMHM demonstrated the best patterning performance among the four resins. These polymers can be applied in the manufacturing of high-density integrated circuits, nano-transistors, optoelectronic devices and other components in the future.

Origin of copper as a unique catalyst for C-C coupling in electrocatalytic CO2 reduction.

High yields of C2 products through electrocatalytic CO2 reduction (eCO2R) can only be obtained using Cu-based catalysts. Here, we adopt the generalized frontier molecular orbital (MO) theory based on first-principles calculations to identify the origin of this unique property of Cu. We use the grand canonical ensemble (or fixed potential) approach to ensure that the calculated Fermi level, which serves as the frontier orbital of the metal catalyst, accurately represents the applied electrode potentials. We determine that the key intermediate OCCO assumes a U-shape configuration with the two C atoms bonded to the Cu substrate. We identify the frontier MOs that are involved in the C-C coupling. The good alignment of the Fermi level of Cu with these frontier MOs is perceived to account for the excellent catalytic performance of Cu for C-C coupling. It is expected that these new insights could provide useful guidance in tuning Cu-based catalysts as well as designing non-Cu catalysts toward high-efficiency eCO2R.

High-Temperature Anomalous Metal States in Iron-Based Interface Superconductors.

The nature of the anomalous metal state has been a major puzzle in condensed matter physics for more than three decades. Here, we report systematic investigation and modulation of the anomalous metal states in high-temperature interface superconductor FeSe films on SrTiO_{3} substrate. Remarkably, under zero magnetic field, the anomalous metal state persists up to 20 K in pristine FeSe films, an exceptionally high temperature standing out from previous observations. In stark contrast, for the FeSe films with nanohole arrays, the characteristic temperature of the anomalous metal state is considerably reduced. We demonstrate that the observed anomalous metal states originate from the quantum tunneling of vortices adjusted by the Ohmic dissipation. Our work offers a perspective for understanding the origin and modulation of the anomalous metal states in two-dimensional bosonic systems.

The Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy.

BACKGROUND: Clearance of damaged mitochondria via mitophagy is crucial for cellular homeostasis. Apart from Parkin, little is known about additional Ub (ubiquitin) ligases that mediate mitochondrial ubiquitination and turnover, particularly in highly metabolically active organs such as the heart. METHODS: In this study, we have combined in silico analysis and biochemical assay to identify CRL (cullin-RING ligase) 5 as a mitochondrial Ub ligase. We generated cardiomyocytes and mice lacking RBX2 (RING-box protein 2; also known as SAG [sensitive to apoptosis gene]), a catalytic subunit of CRL5, to understand the effects of RBX2 depletion on mitochondrial ubiquitination, mitophagy, and cardiac function. We also performed proteomics analysis and RNA-sequencing analysis to define the impact of loss of RBX2 on the proteome and transcriptome. RESULTS: RBX2 and CUL (cullin) 5, 2 core components of CRL5, localize to mitochondria. Depletion of RBX2 inhibited mitochondrial ubiquitination and turnover, impaired mitochondrial membrane potential and respiration, increased cardiomyocyte cell death, and has a global impact on the mitochondrial proteome. In vivo, deletion of the Rbx2 gene in adult mouse hearts suppressed mitophagic activity, provoked accumulation of damaged mitochondria in the myocardium, and disrupted myocardial metabolism, leading to the rapid development of dilated cardiomyopathy and heart failure. Similarly, ablation of RBX2 in the developing heart resulted in dilated cardiomyopathy and heart failure. The action of RBX2 in mitochondria is not dependent on Parkin, and Parkin gene deletion had no impact on the onset and progression of cardiomyopathy in RBX2-deficient hearts. Furthermore, RBX2 controls the stability of PINK1 in mitochondria. CONCLUSIONS: These findings identify RBX2-CRL5 as a mitochondrial Ub ligase that regulates mitophagy and cardiac homeostasis in a Parkin-independent, PINK1-dependent manner.

Effect of substituents at the C3´, C3´N, C10 and C2-meta-benzoate positions of taxane derivatives on their activity against resistant cancer cells.

We tested the effect of substituents at the (1) C3´, C3´N, (2) C10, and (3) C2-meta-benzoate positions of taxane derivatives on their activity against sensitive versus counterpart paclitaxel-resistant breast (MCF-7) and ovarian (SK-OV-3) cancer cells. We found that (1) non-aromatic groups at both C3´ and C3´N positions, when compared with phenyl groups at the same positions of a taxane derivative, significantly reduced the resistance of ABCB1 expressing MCF-7/PacR and SK-OV-3/PacR cancer cells. This is, at least in the case of the SB-T-1216 series, accompanied by an ineffective decrease of intracellular levels in MCF-7/PacR cells. The low binding affinity of SB-T-1216 in the ABCB1 binding cavity can elucidate these effects. (2) Cyclopropanecarbonyl group at the C10 position, when compared with the H atom, seems to increase the potency and capability of the derivative in overcoming paclitaxel resistance in both models. (3) Derivatives with fluorine and methyl substituents at the C2-meta-benzoate position were variously potent against sensitive and resistant cancer cells. All C2 derivatives were less capable of overcoming acquired resistance to paclitaxel in vitro than non-substituted analogs. Notably, fluorine derivatives SB-T-121205 and 121,206 were more potent against sensitive and resistant SK-OV-3 cells, and derivatives SB-T-121405 and 121,406 were more potent against sensitive and resistant MCF-7 cells. (4) The various structure-activity relationships of SB-T derivatives observed in two cell line models known to express ABCB1 favor their complex interaction not based solely on ABCB1.

Band flipping and bandgap closing in a photonic crystal ring and its applications.

The size of the bandgap in a photonic crystal ring is typically intuitively considered to monotonically grow as the modulation amplitude of the grating increases, causing increasingly large frequency splittings between the "dielectric" and "air" bands. In contrast, here we report that as the modulation amplitude in a photonic crystal ring increases, the bandgap does not simply increase monotonically. Instead, after the initial increase, the bandgap closes and then reopens again with the two bands flipped in energy. The air and dielectric band edges are degenerate at the bandgap closing point. We demonstrate this behavior experimentally in silicon nitride photonic crystal microrings, where we show that the bandgap is closed to within the linewidth of the optical cavity mode, whose intrinsic quality factor remains unperturbed with a value ≈ 1×106. Moreover, through finite-element simulations, we show that such bandgap closing and band flipping phenomena exist in a variety of photonic crystal rings with varying unit cell geometries and cladding layers. At the bandgap closing point, the two standing wave modes with a degenerate frequency are particularly promising for single-frequency lasing applications. Along this line, we propose a compact self-injection locking scheme that integrates many core functionalities in one photonic crystal ring. Additionally, the single-frequency lasing might be applicable to distributed-feedback (DFB) lasers to increase their manufacturing yield.

PAHs removal by soil washing with thiacalix[4]arene tetrasulfonate.

Remediating soil contaminated with polycyclic aromatic hydrocarbons (PAHs) presents a significant environmental challenge due to their toxic and carcinogenic properties. Traditional PAHs remediation methods-chemical, thermal, and bioremediation-along with conventional soil-washing agents like surfactants and cyclodextrins face challenges of cost, ecological harm, and inefficiency. Here we show an effective and environmentally friendly calixarene derivative for PAHs removal through soil washing. Thiacalix[4]arene tetrasulfonate (TCAS) has a unique molecular structure of a sulfonate group and a sulfur atom, which enhances its solubility and facilitates selective binding with PAHs. It forms host-guest complexes with PAHs through π-π stacking, OH-π interactions, hydrogen bonding, van der Waals forces, and electrostatic interactions. These interactions enable partial encapsulation of PAH molecules, aiding their desorption from the soil matrix. Our results show that a 0.7% solution of TCAS can extract approximately 50% of PAHs from contaminated soil while preserving soil nutrients and minimizing adverse environmental effects. This research unveils the pioneering application of TCAS in removing PAHs from contaminated soil, marking a transformative advancement in resource-efficient and sustainable soil remediation strategies.

Unveiling the Selectivity of Ru(II)-Catalyzed C-H Activation for Defluorinative Cyclization of 2-Arylbenzimidazole and Trifluoromethyl Diazo: A DFT Study.

The synthesis of monofluorinated heterocyclic compounds by C-H activation combined with defluorination is useful. Studies on the reaction mechanism and selectivity have shown that these processes play a positive role in promoting the development of monofluorinated reactions. Density functional theory (DFT) calculations were performed to investigate the mechanism and selectivity of Ru(II)-catalyzed 2-arylbenzimidazole with trifluoromethyl diazo. DFT calculations showed that C-H activation occurs through a concerted metalation/deprotonation (CMD) mechanism. After that, deprotonation and defluorinative cyclization are assisted by acetate and trifluoroethanol (TFE). Further mechanistic insights through noncovalent interaction (NCI) analysis were also obtained to elucidate the origin of the selectivity in the defluorination process.

Tailoring the selective generation of oxidative organic radicals for toxic-by-product-free water decontamination.

Peracetic acid (PAA) is emerging as a versatile agent for generating long-lived and selectively oxidative organic radicals (R-O•). Currently, the conventional transition metal-based activation strategies still suffer from metal ion leaching, undesirable by-products formation, and uncontrolled reactive species production. To address these challenges, we present a method employing BiOI with a unique electron structure as a PAA activator, thereby predominantly generating CH3C(O)O• radicals. The specificity of CH3C(O)O• generation ensured the superior performance of the BiOI/PAA system across a wide pH range (2.0 to 11.0), even in the presence of complex interfering substances such as humic acids, chloride ions, bicarbonate ions, and real-world water matrices. Unlike conventional catalytic oxidative methods, the BiOI/PAA system degrades sulfonamides without producing any toxic by-products. Our findings demonstrate the advantages of CH3C(O)O• in water decontamination and pave the way for the development of eco-friendly water decontaminations based on organic peroxides.

Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis.

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg-1·d-1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1ß. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1ß, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

Regional structure-function relationships of lumbar cartilage endplates.

Cartilage endplates (CEPs) act as protective mechanical barriers for intervertebral discs (IVDs), yet their heterogeneous structure-function relationships are poorly understood. This study addressed this gap by characterizing and correlating the regional biphasic mechanical properties and biochemical composition of human lumbar CEPs. Samples from central, lateral, anterior, and posterior portions of the disc (n = 8/region) were mechanically tested under confined compression to quantify swelling pressure, equilibrium aggregate modulus, and hydraulic permeability. These properties were correlated with CEP porosity and glycosaminoglycan (s-GAG) content, which were obtained by biochemical assays of the same specimens. Both swelling pressure (142.79 ± 85.89 kPa) and aggregate modulus (1864.10 ± 1240.99 kPa) were found to be regionally dependent (p = 0.0001 and p = 0.0067, respectively) in the CEP and trended lowest in the central location. No significant regional dependence was observed for CEP permeability (1.35 ± 0.97 * 10-16 m4/Ns). Porosity measurements correlated significantly with swelling pressure (r = -0.40, p = 0.0227), aggregate modulus (r = -0.49, p = 0.0046), and permeability (r = 0.36, p = 0.0421), and appeared to be the primary indicator of CEP biphasic mechanical properties. Second harmonic generation microscopy also revealed regional patterns of collagen fiber anchoring, with fibers inserting the CEP perpendicularly in the central region and at off-axial directions in peripheral regions. These results suggest that CEP tissue has regionally dependent mechanical properties which are likely due to the regional variation in porosity and matrix structure. This work advances our understanding of healthy baseline endplate biomechanics and lays a groundwork for further understanding the role of CEPs in IVD degeneration.

Subtype prediction of intrahepatic cholangiocarcinoma using dynamic contrast-enhanced ultrasound.

OBJECTIVE: The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). METHODS: This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. RESULTS: In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p < 0.001), carbohydrate antigen 19-9 (p = 0.004), ill-defined margin (p = 0.018), intrahepatic bile duct dilation (p < 0.001). Among DCE-US quantitative parameters, the wash-out area under the curve (WoAUC), wash-in and wash-out area under the curve (WiWoAUC), and fall time (FT) at the margin of lesions were higher in the SD-type group (all p < 0.05). Meanwhile, the mean transit time (mTT) and wash-out rate (WoR) at the margin of the lesion were higher in the LD-type group (p = 0.041 and 0.007, respectively). Logistic regression analysis showed that intrahepatic bile duct dilation, mTT, and WoR were significant predictive factors for predicting ICC subtypes, and the AUC of the predictive model achieved 0.833 in the test cohort. CONCLUSIONS: Preoperative DCE-US has the potential to become a novel complementary method for predicting the pathological subtype of ICC. CRITICAL RELEVANCE STATEMENT: DCE-US has the potential to assess the subtypes of ICC lesions quantitatively and preoperatively, which allows for more accurate and objective differential diagnoses, and more appropriate treatments and follow-up or additional examination strategies for the two subtypes. KEY POINTS: Preoperative determination of intrahepatic cholangiocarcinoma (ICC) subtype aids in surgical decision-making. Quantitative parameters from dynamic contrast-enhanced US (DCE-US) allow for the prediction of the ICC subtype. DCE-US-based imaging has the potential to become a novel complementary method for predicting ICC subtypes.

The fluoride exporter (CsFEX) regulates fluoride uptake/accumulation in Camellia sinensis under different pH.

Fluoride (F) can be absorbed from the environment and hyperaccumulate in leaves of Camellia sinensis without exhibiting any toxic symptoms. Fluoride exporter in C. sinensis (CsFEX) could transport F to extracellular environment to alleviate F accumulation and F toxicity, but its functional mechanism remains unclear. Here, combining with pH condition of C. sinensis growth, the characteristics of CsFEX and mechanism of F detoxification were further explored. The results showed that F accumulation was influenced by various pH, and pH 4.5 and 6.5 had a greater impact on the F accumulation of C. sinensis. Through Non-invasive Micro-test Technology (NMT) detection, it was found that F uptake/accumulation of C. sinensis and Arabidopsis thaliana might be affected by pH through changing the transmembrane electrochemical proton gradient of roots. Furthermore, diverse expression patterns of CsFEX were induced by F treatment under different pH, which was basically up-regulated in response to high F accumulation, indicating that CsFEX was likely to participate in the process of F accumulation in C. sinensis and this process might be regulated by pH. Additionally, CsFEX functioned in the mitigation of F sensitivity and accumulation strengthened by lower pH in Escherichia coli and A. thaliana. Moreover, the changes of H+ flux and potential gradient caused by F were relieved as well in transgenic lines, also suggesting that CsFEX might play an important role in the process of F accumulation. Above all, F uptake/accumulation were alleviated in E. coli and A. thaliana by CsFEX through exporting F-, especially at lower pH, implying that CsFEX might regulate F accumulation in C. sinensis.

Reconstruction of Craniomaxillofacial Bone Defects with 3D-Printed Bioceramic Implants: Scoping Review and Clinical Case Series.

Reconstruction of craniomaxillofacial bone defects using 3D-printed hydroxyapatite (HA) bioceramic patient-specific implants (PSIs) is a new technique with great potential. This study aimed to investigate the advantages, disadvantages, and clinical outcomes of these implants in craniomaxillofacial surgeries. The PubMed and Embase databases were searched for patients with craniomaxillofacial bone defects treated with bioceramic PSIs. Clinical outcomes such as biocompatibility, biomechanical properties, and aesthetics were evaluated and compared to those of commonly used titanium or poly-ether-ether-ketone (PEEK) implants and autologous bone grafts. Two clinical cases are presented to illustrate the surgical procedure and clinical outcomes of HA bioceramic PSIs. Literature review showed better a biocompatibility of HA PSIs than titanium and PEEK. The initial biomechanical properties were inferior to those of autologous bone grafts, PEEK, and titanium but improved when integrated. Satisfactory aesthetic results were found in our two clinical cases with good stability and absence of bone resorption or infection. Radiological signs of osteogenesis were observed in the two clinical cases six months postoperatively. HA bioceramic PSIs have excellent biocompatible properties and imitate natural bone biomechanically and radiologically. They are a well-suited alternative for conventional biomaterials in the reconstruction of load-sharing bone defects in the craniomaxillofacial region.