Charting facial growth and development for Bantu Africans: Central tendencies, variational properties and sexual dimorphisms.

Current studies on facial growth and development have been largely based on European populations. Less studied are African populations, who because of their distinct genetic makeup and environmental conditions, provide deeper insights into patterns of facial development. Patterns of facial shape development in African populations remain largely uncharacterised. Our study aimed to establish facial growth and development trajectories based on a cohort of 2874 Bantu Africans from Tanzania aged 6-18 years, with particular focus on identifying morphogenetic processes that lead to observed developmental shape changes. Procrustes ANCOVA suggested sexually dimorphic patterns of facial shape development (p = 0.0036). The forehead was relatively contracted during development in both sexes. The glabella region was more anteriorly displaced in females due to expansion in the region laterosuperior to the eyes. Nasal protrusion increased with development, which was found to arise from local expansion in the nasal alae and columella. Local expansion in the upper and lower labial regions resulted in forward displaced lips in both sexes, with the effect more pronounced in males. The mentum was displaced more anteriorly in females due to comparatively more expanded mental regions with development. The lateral facial region corresponding to the underlying body of the mandible were developmentally expanded but were posteriorly positioned due to protrusive growth of surrounding structures. Generalised additive modelling of Procrustes variance suggested that facial variation decreased non-linearly with age (p < 0.05). Relative principal component analysis suggested that variations in facial outline shape were developmentally constrained, whereas nasolabial and mental regions, where developmental changes were significant, became morphologically diversified with development. In contrast to simple descriptive illustration of facial shape development, we gained transformative insights into patterns of facial shape development by analysing morphogenetic processes and variational properties. Our analytical framework is broadly applicable to morphometric studies on ontogenetic shape changes.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

Kinetic reaction mechanism of lignocellulosic biomass oxidative pyrolysis based on combined kinetics.

The kinetics knowledge of lignocellulosic biomass decomposition is essential to develop efficient thermochemical conversion technology. However, the simplification of reaction mechanisms in existing oxidative pyrolysis studies largely compromises the application of kinetic models. To explore more exact kinetic parameters and reaction mechanism of lignocellulosic biomass oxidative pyrolysis, an updated oxidative pyrolysis kinetic model (seven-step reaction combined kinetics model) coupled with an optimization algorithm is proposed. Based on a series of thermogravimetric experiments in an air atmosphere, the extra oxidative pyrolysis kinetic parameters are obtained by the Shuffled Complex Evolution method. The proposed kinetic model is validated based on the degradation process of each component (hemicellulose, cellulose, and lignin). Furthermore, the obtained kinetic parameters are applied to predict the oxidative pyrolysis behavior, and the predicted mass loss rate is in good agreement with the experimental data. Eventually, according to the key combined kinetics parameters, it is found that the oxidative pyrolysis mechanisms of hemicellulose, cellulose, and lignin correspond to the power law, nucleation & growth, and chemical reaction order, respectively, while the combustion of char corresponds to the reaction order mechanism.

How to Determine a Suitable Alginate for Biofabrication Approaches using an Extensive Alginate Library?

Alginate-based hydrogels are a promising class of biomaterials due to their usability, biocompatibility, and high water-binding capacity which is the reason for their broad use in biofabrication. One challenge of these biomaterials is, however, the lack of cell adhesion motifs. This drawback can be overcome by oxidizing alginate to alginate dialdehyde (ADA) and by subsequent cross-linking with gelatin (GEL) to fabricate ADA-GEL hydrogels, which offer improved cell-material interactions. The present work investigates four pharmaceutical grade alginates of different algae sources and their respective oxidized forms regarding their molecular weight and M/G ratio using 1H NMR spectroscopy and gel permeation chromatography. In addition, three different methods for determining the degree of oxidation (% DO) of ADA, including iodometric, spectroscopic, and titration methods, are applied and compared. Furthermore, the aforementioned properties are correlated with the resulting viscosity, degradation behavior, and cell-material interactions to predict the material behavior in vitro and thus choose a suitable alginate for an intended application in biofabrication. In the framework of the present work, easy and practicable detection methods for the investigations of alginate-based bioinks were summarized and shown. In this regard, the success of oxidation of alginate was confirmed by the three aforementioned methods and was further proven by solid-state 13C NMR, for the first time in the literature, that only guluronic acid (G) was attacked during the oxidation, leading to the formation of hemiacetals. Furthermore, it was shown that ADA-GEL hydrogels of alginates with longer G-blocks are more suitable for long-term experiments due to their stability over an incubation period of 21 days, while ADA-GEL hydrogels of alginates with longer mannuronic acid (M)-blocks are more suitable for short-term applications such as sacrificial inks due to their extensive swelling and subsequent loss of shape. Finally, it was proven that the M/G ratio did not show any influence on the biocompatibility or printability of the investigated alginate-based hydrogels. The physicochemical findings provide an alginate library for tailored application in biofabrication.

Global, regional, and national burden of severe periodontitis, 1990-2019: An analysis of the Global Burden of Disease Study 2019.

AIM: Up-to-date epidemiological studies on the global burden of severe periodontitis is scarce. This study aimed to present the latest estimates for prevalence of severe periodontitis from 1990 to 2019, by region, age, and level of socio-demographic development. MATERIALS AND METHODS: Estimates from the Global Burden of Disease study 2019 were used to investigate burden and trends of prevalence of severe periodontitis and its association with socio-demographic development at global, regional, and national level. Decomposition analysis was performed to explore the contribution of demographic and epidemiological factors to the evolving burden of severe periodontitis. RESULTS: In 2019, there were 1.1 billion (95% uncertainty interval: 0.8-1.4 billion) prevalent cases of severe periodontitis globally. From 1990 to 2019, age-standardized prevalence rate of severe periodontitis increased by 8.44% (6.62%-10.59%) worldwide. Prevalence of severe periodontitis is higher among less developed countries/regions. Global population growth accounted for 67.9% of the increase in the number of prevalent cases of severe periodontitis from 1990 to 2019. CONCLUSIONS: The global burden of severe periodontitis has been substantial and increasing over the past three decades. Upstream policy changes are urgently needed to address the global public health challenge of severe periodontitis.

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial.

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.

Fibre-specific regulation of lignin biosynthesis improves biomass quality in Populus.

Lignin is a major component of cell wall biomass and decisively affects biomass utilisation. Engineering of lignin biosynthesis is extensively studied, while lignin modification often causes growth defects. We developed a strategy for cell-type-specific modification of lignin to achieve improvements in cell wall property without growth penalty. We targeted a lignin-related transcription factor, LTF1, for modification of lignin biosynthesis. LTF1 can be engineered to a nonphosphorylation form which is introduced into Populus under the control of either a vessel-specific or fibre-specific promoter. The transgenics with lignin suppression in vessels showed severe dwarfism and thin-walled vessels, while the transgenics with lignin suppression in fibres displayed vigorous growth with normal vessels under phytotron, glasshouse and field conditions. In-depth lignin structural analyses revealed that such cell-type-specific downregulation of lignin biosynthesis led to the alteration of overall lignin composition in xylem tissues reflecting the population of distinctive lignin polymers produced in vessel and fibre cells. This study demonstrates that fibre-specific suppression of lignin biosynthesis resulted in the improvement of wood biomass quality and saccharification efficiency and presents an effective strategy to precisely regulate lignin biosynthesis with desired growth performance.

Self-Assembled ROS-Sensitive Polymer-Peptide Therapeutics Incorporating Built-in Reporters for Evaluation of Treatment Efficacy.

One of the major challenges in current cancer therapy is to maximize therapeutic effect and evaluate tumor progression under the scheduled treatment protocol. To address these challenges, we synthesized the cytotoxic peptide (KLAKLAK)2 (named KLAK) conjugated amphiphilic poly(ß-thioester)s copolymers (H-P-K) composed of reactive oxygen species (ROS) sensitive backbones and hydrophilic polyethylene glycol (PEG) side chains. H-P-K could self-assemble into micelle-like nanoparticles by hydrophobic interaction with copolymer backbones as cores and PEG and KLAK as shells. The assembled polymer-peptide nanoparticles remarkably improved cellular internalization and accumulation of therapeutic KLAK in cells. Compared to free KLAK peptide, the antitumor activity of H-P-K was significantly enhanced up to ∼400 times, suggesting the effectiveness of the nanoscaled polymer-peptide conjugation as biopharmaceuticals. The higher antitumor activity of nanoparticles was attributed to the efficient disruption of mitochondrial membranes and subsequent excessive ROS production in cells. To realize the ROS monitoring and treatment evaluation, we encapsulated squaraine (SQ) dyes as built-in reporters in ROS-sensitive H-P-K micelles. The overgenerated ROS around mitochondria stimulated the swelling of nanoparticles and subsequent release of SQ, which formed H-aggregates and significantly increased the photoacoustic (PA) signal. We believed that this self-assembled polymer-peptide nanotherapeutics incorporating built-in reporters has great potential for high antitumor performance and in situ treatment evaluation.

Cross-linked supramolecular polymer gels constructed from discrete multi-pillar[5]arene metallacycles and their multiple stimuli-responsive behavior.

A new family of discrete hexakis-pillar[5]arene metallacycles with different sizes have been successfully prepared via coordination-driven self-assembly, which presented very few successful examples of preparation of discrete multiple pillar[n]arene derivatives. These newly designed hexakis-pillar[5]arene metallacycles were well characterized with one-dimensional (1-D) multinuclear NMR ((1)H and (31) P NMR), two-dimensional (2-D) (1)H-(1)H COSY and NOESY, ESI-TOF-MS, elemental analysis, and PM6 semiempirical molecular orbital methods. Furthermore, the host-guest complexation of such hexakis-pillar[5]arene hosts with a series of different neutral ditopic guests G1-6 were well investigated. Through host-guest interactions of hexakis-pillar[5]arene metallacycles H2 or H3 with the neutral dinitrile guest G5, the cross-linked supramolecular polymers H2⊃(G5)3 or H3⊃(G5)3 were successfully constructed at the high-concentration region, respectively. Interestingly, these cross-linked supramolecular polymers transformed into the stable supramolecular gels upon increasing the concentrations to a relatively high level. More importantly, by taking advantage of the dynamic nature of metal-ligand bonds and host-guest interactions, the reversible multiple stimuli-responsive gel-sol phase transitions of such polymer gels were successfully realized under different stimuli, such as temperature, halide, and competitive guest, etc. The mechanism of such multiple stimuli-responsive processes was well illustrated by in situ multinuclear NMR investigation. This research not only provides a highly efficient approach to the preparation of discrete multiple pillar[n]arene derivatives but also presents a new family of multiple stimuli-responsive "smart" soft matters.

Electrical detection of nucleic acid amplification using an on-chip quasi-reference electrode and a PVC REFET.

Electrical detection of nucleic acid amplification through pH changes associated with nucleotide addition enables miniaturization, greater portability of testing apparatus, and reduced costs. However, current ion-sensitive field effect transistor methods for sensing nucleic acid amplification rely on establishing the fluid gate potential with a bulky, difficult to microfabricate reference electrode that limits the potential for massively parallel reaction detection. Here we demonstrate a novel method of utilizing a microfabricated solid-state quasi-reference electrode (QRE) paired with a pH-insensitive reference field effect transistor (REFET) for detection of real-time pH changes. The end result is a 0.18 µm, silicon-on-insulator, foundry-fabricated sensor that utilizes a platinum QRE to establish a pH-sensitive fluid gate potential and a PVC membrane REFET to enable pH detection of loop mediated isothermal amplification (LAMP). This technique is highly amendable to commercial scale-up, reduces the packaging and fabrication requirements for ISFET pH detection, and enables massively parallel droplet interrogation for applications, such as monitoring reaction progression in digital PCR.

Ultrasensitive amperometric determination of hand, foot and mouth disease based on gold nanoflower modified microelectrode.

Given the widespread use of point-of-care testing for diagnosis of disease, micro-scale electrochemical deoxyribonucleic acid (DNA) biosensors have become a promising area of research owing to its fast mass transfer, high current density and rapid response. In this study, a gold nanoparticles modified gold microelectrode (AuNPs/Au-Me) was constructed to determine the hand, foot and mouth disease (HFMD)-related gene. The noble metal nanoparticles modification yielded ca. 7.4-fold increase in electroactive surface area of microelectrode, and the signal for HFMD-related gene was largely magnified. Under optimal conditions, the biosensor exhibited salient selectivity and sensitivity with a low detection limit of 0.3 fM (S/N = 3), which is sufficient for clinical diagnosis of HFMD. Additionally, the developed AuNPs/Au-Me was successfully applied to determining the polymerase chain reaction (PCR) amplified products of target gene. Thus, the electrochemical DNA biosensor possesses great potential in early-stage diagnosis and long-term monitoring of various disease.

A Y-shape-structured electrochemiluminescence biosensor based on carbon quantum dots and locked nucleic acid probe for microRNA determination with single-base resolution.

Since microRNAs (miRNAs) are predictors of tumorigenesis, accurate identification and quantification of miRNAs with highly similar sequences are expected to reflect tumor diagnosis and treatment. In this study, a highly selective and sensitive electrochemiluminescence (ECL) biosensor was constructed for miRNAs determination based on Y-shaped junction structure equipped with locked nucleic acids (LNA), graphene oxide-based nanocomposite to enrich luminophores, and conductive matrix. Specifically, two LNA-modified probes were designed for specific miRNA recognition, that is, a dual-amine functionalized hairpin capture probe and a signal probe. A Y-shaped DNA junction structure was generated on the electrode surface upon miRNA hybridizing across the two branches, so as to enhance the selectivity. Carbon quantum dots-polyethylene imine-graphene oxide (CQDs-PEI-GO) nanocomposites were developed to enrich luminophores CQDs, and thus enhancing the ECL intensity. For indirect signal amplification, an electrochemically activated poly(2-aminoterephthalic acid) (ATA) film decorated with gold nanoparticles was prepared on electrode as an effective matrix to accelerate the electron transfer. The fabricated ECL biosensor achieved sensitive determination of miRNA-222 with a limit-of-detection (LOD) as low as 1.95 fM (S/N = 3). Notably, Y-shaped junction structures equipped with LNA probes endowed ECL biosensor with salient single-base discrimination ability and anti-interference capacity. Overall, the proposed Y-shaped ECL biosensor has considerable promise for clinical biomarker determination.

Preparation of garlic stem cellulose nanocrystal/leaf extract/chitosan film for black garlic preservation by electrostatic spraying.

In this study, a novel active chitosan (CH) packaging film that incorporates garlic leaf extract (GL) and stem cellulose nanocrystals (CNC) was prepared. The addition of CNC to the CH film increased its tensile strength, hydrophilicity, thermal stability, and water/oxygen barrier and decreased its water contact angle and weight-loss rate, while the addition of GL greatly enhanced its antioxidant and antibacterial activities. SEM and AFM analyses showed that the CNC agglomerates and deposits in the lower layer and the surface roughness of the film was the highest at 1.2 % concentration. The optimal composition of the film was determined to be 0.8 % CNC and 4 % GL by the fuzzy mathematics evaluation method. Then, black garlic was preserved with the optimized coating by electrostatic spraying and was found to slow water loss and migration, while its excellent antioxidant activities decreased the degree of browning during 90 d of storage.

Burden, Trends, and Inequality of Dental Caries in the U.S., 1990-2019.

INTRODUCTION: Over the past 2 decades in the U.S., the reduced burden and narrowed inequality in oral health among children are in stark contrast with the high burden and widening inequality in adult oral health. This study aimed to explore the burden, trends, and inequalities of untreated caries in permanent teeth in the U.S. during 1990-2019. METHODS: Data on burden of untreated caries in permanent teeth were extracted from the Global Burden of Disease Study 2019. A set of advanced analytical methods were applied to provide an in-depth characterization of the epidemiologic profile of dental caries in the U.S. Analyses were conducted during April 2022-October 2022. RESULTS: In 2019, age-standardized incidence and prevalence of untreated caries in permanent teeth were respectively 39,111.7 (95% uncertainty interval=35,073.0-42,964.9) and 21,722.5 (95% uncertainty interval=18,748.7-25,090.3) per 100,000 person-years. Population growth was the primary driver of the increased caries cases, which contributed 31.3% and 31.0% of the increase in the number of incident and prevalent caries cases, respectively, during 1990-2019. The highest caries burden was noted in Arizona, West Virginia, Michigan, and Pennsylvania. The slope index of inequality remained stable (p=0.076), whereas the relative index of inequality increased significantly (average annual percent change=0.04, p<0.001) in the U.S. The burden of untreated caries in permanent teeth remained significant with a widening cross-state inequality during 1990-2019. CONCLUSIONS: The oral healthcare system in the U.S. needs to prioritize health promotion and prevention with a focus on expanding access, affordability, and equity.

Gene liposome nanocomplex-loaded dermal substitute promotes diabetic chronic wound healing and angiogenesis in rat.

The incidence of chronic diabetic wounds is increasing with the growing number of diabetic patients, and conventional wound dressings have proven to be ineffective in treating them. To address this challenge, researchers have developed artificial dermal substitutes using collagen and hyaluronic acid, which are crucial extracellular matrices. However, these subsitiues lack precision and targeted treatment. To overcome this limitation, a gene liposome nanocomplex-loaded dermal substitute (GDS) has been developed as a potential solution. This innovative biomaterial combines the benefits of liposome nanocomplexes with dermal substitutes to offer a more accurate and effective treatment option for chronic diabetic wounds. The GDS has the ability to deliver genes and therapeutic agents specifically to the wound site, promoting angiogenesis and accelerating the wound healing process. Overall, the GDS presents a promising new approach for the clinical treatment of chronic diabetic wounds, offering a targeted and effective solution for this growing problem.

Exploring the mechanism of Akebia trifoliata fruit cracking based on cell-wall metabolism.

Akebia trifoliata fruit cracks easily, but little is known about the underlying mechanism of this process. In this study, the changes in minerals contents, water distribution, phytohormone levels, and reactive oxygen species (ROS) metabolism were investigated to explore the effects of cell-wall metabolism in A. trifoliata fruit cracking. The micro-morphological observation confirmed that A. trifoliata fruit cracking was closely related to the cell-wall metabolism. After cracking, the higher polygalacturonase, ß-1,4-endoglucanase, and ß-glucosidase activities resulted in the depolymerization of covalently bound pectin (from 9.69% to 7.70%) and cellulose (from 57.91% to 38.05%). Moreover, the disordered ROS homeostasis resulted from the lower superoxide dismutase and ascorbate peroxidase activities, which led to cellular oxidative damage. These modifications, together with the decreases in Ca, K, and B, degradation of starch, and the movement of water, decreased cell-wall strength and degraded the cellulose network, and thus resulted in A. trifoliata cracking. The above processes were regulated by phytohormones through increased indole-3-acetic acid, salicylic acid, and jasmonic acid levels, as well as decreased cytokinin content. The findings of this study will be beneficial for further research into the preservation of A. trifoliata fruit, which is of great significance to the development of the A. trifoliata industry.

Electrochemical monitoring the effect of drug intervention on PC12 cell damage model cultured on paper-PLA 3D printed device.

Three-dimensional (3D) cell culture system, as an alternative approach for traditional cell culture, attracts great attention because of physiological relevance and great microenvironment similarity to human conditions. Herein, a facile paper-polylactic (PLA) platform that was fabricated by wax printing and 3D printing, coupled with electrochemical sensor, was designed for the construction and intervention of 3D cell damage model. Pheochromocytoma cells (PC12) and bone marrow mesenchymal stem cells (BMSCs) were seeded on the paper-PLA 3D platforms and displayed the features of uniform distribution, good adhesion and perfect proliferation, as well as decreased circularity when compared to those grown on the two-dimensional (2D) interfaces. The electrochemical sensors revealed cell viability by monitoring dopamine released by cell models, ascertaining the applicability of the paper-PLA platform to a long-term 3D cell culture and drug assessment. Additionally, the results revealed that donepezil and BMSCs-secreted active molecules exhibited stronger cytoprotective effect against amyloid-beta oligomers-induced cell damage on the paper-PLA 3D printed platforms, indicating the cell damage model and the cell intervention model were achieved successfully in the simulated in vivo physiological microenvironment. Thus, the proposed paper-PLA platform may serve as a promising candidate for efficient drug screening and toxicity evaluation due to its simple structure, low cost, and convenient integration of 3D cell culture and activity evaluation.

New Progress in Improving the Delivery Methods of Bisphosphonates in the Treatment of Bone Tumors.

Bone tumors are tumors that occur in the bone or its accessory tissues, including primary tumors and metastatic tumors. The main mechanism of bisphosphonate is to inhibit the resorption of destructive bone, inhibit the activity of osteoclasts and reduce the concentration of blood calcium. Therefore, bisphosphonates can be used for malignant hypercalcaemia, pain caused by osteolytic bone metastasis, prevention of osteolytic bone metastasis, multiple myeloma osteopathy, improving radiosensitivity and so on. However, the traditional administration of bisphosphonates can cause a series of adverse reactions. To overcome this disadvantage, it is necessary to develop novel methods to improve the delivery of bisphosphonates. In this paper, the latest research progress of new and improved bisphosphonate drug delivery methods in the treatment of bone tumors is reviewed. At present, the main design idea is to connect bisphosphonate nanoparticles, liposomes, microspheres, microcapsules, couplings, prodrugs and bone tissue engineering to targeted anti-tumors systems, and positive progress has been made in in vitro and animal experiments. However, its safety and effectiveness in human body still need to be verified by more studies.

Biosynthesis of α-Pinene by Genetically Engineered Yarrowia lipolytica from Low-Cost Renewable Feedstocks.

α-Pinene, an important biologically active natural monoterpene, has been widely used in fragrances, medicines, and fine chemicals, especially, in high-density renewable fuels such as jet fuel. The development of an α-pinene production platform in a highly modifiable microbe from renewable substitute feedstocks could lead to a green, economical avenue, and sustainable biotechnological process for the biosynthesis of α-pinene. Here, we report engineering of an orthogonal biosynthetic pathway for efficient production of α-pinene in oleaginous yeast Yarrowia lipolytica that resulted in an α-pinene titer of 19.6 mg/L when using glucose as the sole carbon source, a significant 218-fold improvement than the initial titer. In addition, the potential of using waste cooking oil and lignocellulosic hydrolysate as carbon sources for α-pinene production from the engineered Y. lipolytica strains was analyzed. The results indicated that α-pinene titers of 33.8 and 36.1 mg/L were successfully obtained in waste cooking oil and lignocellulosic hydrolysate medium, thereby representing the highest titer reported to date in yeast. To our knowledge, this is also the first report related to microbial production of α-pinene from waste cooking oil and lignocellulosic hydrolysate.

Effect of plastic film mulching and film residues on phthalate esters concentrations in soil and plants, and its risk assessment.

The application of plastic film mulching can greatly improve dryland productivity, while the release of toxic phthalate esters (PAEs) from the plastic film has generated concern. This study investigated the effects of mulched plastic film and residual plastic film on the PAE concentrations in the soil-crop system and assessed the risks to people eating crop products. The PAEs concentration in the 0-25 cm soil layer of plastic mulched farmland was 0.45-0.81 mg/kg, while the average PAEs concentration of 0.37-0.73 mg/kg in non-mulched farmland decreased by 19%. The PAEs concentration in mulched soil reached the highest in July, being 0.80-0.84 mg/kg, while in the non-mulched soil, the PAEs also appeared and gradually decreased from May at 0.62-0.74 mg/kg to October, and the PAEs concentrations were almost the same in the mulched and non-mulched soils at the harvest time in October at 0.37-0.44 mg/kg. With the amounts of residual film in farmland increasing from 0 kg/ha to 2700 kg/ha (equivalent to the total amount of residual film after 60 years of continuous plastic film mulching), the PAEs concentrations were no significant changes, being 0.54-0.93 mg/kg. Maize (Zea mays L.) roots could absorb and accumulate PAEs, and the bio-concentration factor (BCF) was 1.6-2.3, and the average PAEs concentrations in stems, leaves, and grains were 79%-80% of those in roots at 0.77-1.47 mg/kg. For the ingestion of maize grains or potato (Solanum tuberosum L.) tubers grown in plastic film mulched farmland or farmland containing residual film of 450-2700 kg/ha, the hazard index (HI) were less than 1, the carcinogenic risks (CRs) were 2.5 × 10-7-2.2 × 10-6, and the estrogenic equivalences were 6.17-17.73 ng E2/kg. This study provides important data for the risk management of PAEs in farmlands.