Feasibility of Amide Proton Transfer-Weighted Imaging at 3T for Renal Masses: A Preliminary Study.

BACKGROUND: To investigate the optimal B1,rms value of renal amide proton transfer-weighted (APTw) images and the reproducibility of this value, and to explore the utility of APT imaging of renal masses and kidney tissues. METHODS: APTw images with different B1,rms values were repeatedly recorded in 15 healthy volunteers to determine the optimal value. Two 4-point Likert scales (poor [1] to excellent [4]) were used to evaluate contour clarity and artifacts in masses and normal tissues. The APTw values of masses and normal tissues were then compared in evaluable images (contour clarity score > 1, artifacts score > 1). The APTw of malignant masses, normal tissues, and benign masses were calculated and compared with the Mann-Whitney U test. RESULTS: The optimal scanning parameter of B1,rms was 2 µT, and the APTw images had good agreement in the volunteers. Our study of APTw imaging examined 70 renal masses (13 benign, 57 malignant) and 49 normal kidneys (including those from 15 healthy volunteers). The mean APTw value for renal malignant masses (2.28(1.55)) was different from that for benign masses (0.91(1.30)) (P<0.001), renal cortex (1.30 (1.25)) (P<0.001), renal medulla (1.64 (1.33)) (P<0.05), and renal pelvis (5.49 (2.65)) (P<0.001). CONCLUSION: These preliminary data demonstrate that APTw imaging of the kidneys has potential use as an imaging biomarker for the differentiation of normal tissues, malignant masses, and benign masses.

Effect of borax-modified activator on mechanical properties and drying shrinkage of alkali-activated slag/metakaolin mortar.

Alkali-activated materials (AAMs) possess several advantages, such as high strengths and low carbon emissions. However, their application is hindered due to their significant shrinkage. This study explored the effect of borax-modified sodium silicate activator and metakaolin (MK) on the mechanical properties and drying shrinkage (DS) of alkali-activated slag (AAS) and AAS/MK (AASM) mortars. X-ray diffraction, scanning electron microscopy, and Fourier-transform infrared spectroscopy were used to characterize the hydration products. The results showed that the DS reduction of the AAS mortar was related to decreased Na2O content, a reduction in the proportion of mesopores, and the formation of moisture-retaining borate compounds. The DS reduction of the AASM mortar was attributed to the ultra-fine differential effect induced by MK, reducing the connected pores. The modified activator combined with MK increased the chemically bound water content in the matrix. Additionally, the B-O bond and highly active MK improved compactness of the AASM mortar. The use of borax-modified activators and MK provides a new solution to address the significant shrinkage issue in AAMs. This sets the stage for AAMs to potentially replace OPC, contributing to low-carbon emissions and promoting environmental protection.

Comparison of the specific energies of sinusoidal VCS cutter rings and CCS cutter rings in breaking rock-like materials based on the FEM.

Disc cutters are essential for full-section hard-rock tunnel boring machines. The performance of these devices directly affects tunnel engineering costs and duration. This paper proposes a sinusoidal variable cross-section (VCS) cutter ring and design method and establishes a digital model. Rock-like materials are simulated with a finite element model, and the model validity is verified via rock simulation mechanics tests. A disc cutter rolling rock simulation model for a linear cutting machine is also established, and simulation tests are performed for single- and three-cutter rolling using sinusoidal VCSs and constant cross-section (CCS) cutter models, respectively. The stress and energy changes for the cutters and rock-like material damage area were compared via simulation, confirming that some sinusoidal VCS cutter rings do less work on rock-like materials and cause larger crushing areas under the same engineering parameters; therefore, these cutter rings have smaller specific energies. The sinusoidal VCS cutter ring performance is 7% greater than that of CCS on average under single-cutter simulation, and the intermediate cutter performance of the intermediate cutter is 9% greater than that of CCS on average under three-cutter simulation. Thus, sinusoidal VCS cutter rings offer improved rock damage performance, and further research and application of this technology will improve the working efficiency of tunnel boring machines.

A durable hydrophobic photothermal membrane based on a honeycomb structure MXene for stable and efficient solar desalination.

Solar powered water evaporation is a green and environmentally friendly water treatment technology, which is a hot research topic for water purification at present. Advanced structural design and hydrophilic photothermal materials have achieved efficient solar evaporation of pure water, but the long-term stability of high salinity desalination has become a problem that cannot be ignored in practical applications. In order to solve this problem, a hydrophobic honeycomb structure MXene/AuNFs composite membrane was proposed in this paper, which used the three-dimensional highly porous microstructure of MXene and multibranched structure of gold nanoflowers particles to improve the light absorption and photothermal conversion efficiency of MXene/AuNFs. At the same time, the surface of the composite membrane was modified with hydrophobic fluorosilane 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PFTE). The hydrophobic layer can prevent the accumulation of salt particles on the surface of the membrane, so that the composite film can continue to produce water vapor in a high salt environment. With high utilization rate of light energy, multiple-level geometrical structures of MXene for rapid water transport on the filter membrane and salt barrier on the membrane good stability, the hydrophobic MXene/AuNFs achieves solar evaporation rate of 1.59 kg m-2 h-1 and solar conversion efficiency is 97.8%, and stable operation under simulated sea water conditions under one sun irradiation over more than 10 cycles. The hydrophobic MXene/AuNFs membrane proved to be an efficient and stable photothermal material for solar desalination.

Protective effects of emodin on subchondral bone and articular cartilage in osteoporotic osteoarthritis rats: A preclinical study.

BACKGROUND: Osteoporotic osteoarthritis (OP-OA) is a severe pathological form of OA, urgently requiring precise management strategies and more efficient interventions. Emodin (Emo), an effective ingredient found in the traditional Chinese medicine rhubarb, has been dEmonstrated to promote osteogenesis and inhibit extracellular matrix degradation. In this study, we aimed to investigate the interventional effects of Emo on the subchondral bone and cartilage of the knee joints in OP-OA model rats. METHODS: Thirty-two SD rats were randomly and equally divided into sham, OP-OA, Emo low-dose, and Emo high-dose groups. Micro-CT scanning was conducted to examine the bone microstructure of the rat knee joints. H&E and Safranin O and Fast Green staining (SO&FG) were performed for the pathomorphological evaluation of the rat cartilage tissues. ELISA was used to estimate the rat serum expression levels of inflammatory factors, including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Additionally, the CCK-8 assay was utilized for determining the viability of Emo-treated BMSCs. Western blot and real-time PCR analyses were also employed to measure the bone formation indexes and cartilage synthesis and decomposition indexes. Lastly, the osteogenic and chondrogenic differentiation efficiency of the BMSCs was investigated via Alizarin Red and Alcian Blue staining. RESULTS: Emo intervention alleviated the bone microstructural disruption of the subchondral bone and articular cartilage in the OP-OA rats and up-regulated the expression of bone and cartilage anabolic metabolism indicators, decreased the expression of cartilage catabolism indicators, and diminished the expression of inflammatory factors in the rat serum (P<0.05). Furthermore, Emo reversed the decline in the osteogenic and chondrogenic differentiation ability of the BMSCs (P<0.05). CONCLUSION: Emo intervention mitigates bone loss and cartilage damage in OP-OA rats and promotes the osteogenic and chondrogenic differentiation of BMSCs.

Azasulfur(iv) derivatives of sulfite and sulfinate esters by formal S-S bond insertion of dichloramines.

Azasulfur(vi) compounds such as sulfoximines and sulfonimidamides are attractive due to the unique properties of the S[double bond, length as m-dash]N bond. While the synthesis of these carbon-attached sulfonimidoyl derivatives is well-established, the situation is different for their heteroatom-bound counterparts. In this work, we propose azasulfur(iv) esters as platform chemicals that can be derivatized to obtain all types of SVI[double bond, length as m-dash]N functional groups, among these are the poorly accessible, all-heteroatom imidosulfate esters. Using a chloroamination workflow established here, S-S bond-containing structures such as elemental sulfur or diaryl disulfides can be transformed into imidothionyl or sulfinimidoyl chlorides, which are easily esterified or amidated. Thus, chloramines serve as a versatile [N] and [Cl+] source, and by using them in the context reported here, we advance the set of mild synthetic methods as the latest toolbox member to cover even more of the azasulfur(iv) and (vi) chemical space.

Riddle of the Sphinx: Emerging role of circular RNAs in cervical cancer.

Cervical cancer is a prominent cause of cancer-related mortality among women, with recent attention directed toward exploring the involvement of circular RNAs (circRNAs) in this particular cancer. CircRNAs, characterized by a covalently closed loop structure, belong to a class of single-stranded non-coding RNA (ncRNA) molecules that play crucial roles in cancer development and progression through diverse mechanisms. The abnormal expression of circRNAs in vivo is significantly associated with the development of cervical cancer. Notably, circRNAs actively interact with miRNAs in cervical cancer, leading to the regulation of diverse signaling pathways, and they can contribute to cancer hallmarks such as self-sufficiency in growth signals, insensitivity to antigrowth signals, limitless proliferation, evading apoptosis, tissue invasion and metastasis, and sustained angiogenesis. Moreover, the distinctive biomedical attributes exhibited by circRNAs, including their abundance, conservation, and stability in body fluids, position them as promising biomarkers for various cancers. In this review, we elucidate the tremendous potential of circRNAs as diagnostic markers or therapeutic targets in cervical cancer by expounding upon their biogenesis, characteristics, functions, and databases, highlighting the novel advances in the signaling pathways associated with circRNAs in cervical cancer.

Investigation on multi-parameter of hydrate-bearing synthetic sediment during hydrate replacement process: A in-situ X-ray computed tomography study.

Carbon sequestration can be achieved by carbon dioxide replacement in natural gas hydrate exploitation, which reducing greenhouse gas emissions and providing an effective solution to address climate change, while simultaneously protecting the environment and promoting sustainable energy development. Gas replacement can achieve gas exploitation, gas storage, and stability enhancement simultaneously. However, time-varying microstructure evolution of the hydrate-bearing sediment (HBS) during this process remain a large amount of uncertainty. In this study, with microfocus computer tomography, hydrate replacement process is realized using xenon gas to replace krypton hydrate. During this period, the initial hydrate saturation and effective confining pressure were 63 % and 1 MPa respectively, the results were obtained as follows: 1. Hydrate occurrence dynamically adjusted during replacement process due to the "barrier effect" and "diffusion effect". 2. Dissociated water migration occurred in the sediment, and this induced local hydrate enrichment temporarily and blockages, but the blockages were eventually dredged with the dissociation of the Kr hydrate. 3. The sphericity and surface roughness of the hydrate particles were slightly improved, the pore space connectivity was well enhanced, and both tortuosity and absolute permeability was better strengthened after replacement process, where the absolute permeability was increased by 225.23 %, though the blockage occurrence temporarily weakened this strengthener.

Guided diffusion for molecular generation with interaction prompt.

Molecular generative models have exhibited promising capabilities in designing molecules from scratch with high binding affinities in a predetermined protein pocket, offering potential synergies with traditional structural-based drug design strategy. However, the generative processes of such models are random and the atomic interaction information between ligand and protein are ignored. On the other hand, the ligand has high propensity to bind with residues called hotspots. Hotspot residues contribute to the majority of the binding free energies and have been recognized as appealing targets for designed molecules. In this work, we develop an interaction prompt guided diffusion model, InterDiff to deal with the challenges. Four kinds of atomic interactions are involved in our model and represented as learnable vector embeddings. These embeddings serve as conditions for individual residue to guide the molecular generative process. Comprehensive in silico experiments evince that our model could generate molecules with desired ligand-protein interactions in a guidable way. Furthermore, we validate InterDiff on two realistic protein-based therapeutic agents. Results show that InterDiff could generate molecules with better or similar binding mode compared to known targeted drugs.

Enhanced Surgical Outcomes of Popliteal Cyst Excision: A Retrospective Study Comparing Arthroscopic Debridement with and without Methylene Blue Injection.

BACKGROUND This retrospective study of 42 patients with popliteal cysts (or Baker cysts) aimed to compare the effects on duration and outcomes of arthroscopic surgical debridement with and without the use of cyst injection with methylene blue (MB). MATERIAL AND METHODS Medical records of patients who underwent conventional arthroscopic surgery (n=20) or arthroscopic surgery after MB injection (n=22) for popliteal cysts between 2018 and 2021 were reviewed. The MB group underwent arthroscopic popliteal cystectomy with MB as the marker, and the control group underwent conventional arthroscopic popliteal cystectomy. Surgical time of cyst resection, postoperative bruising extent, complication rate, and cyst recurrence rate of the 2 groups were compared. RESULTS The MB group had a faster surgical cyst removal time (16.5±1.5 min) than the control group (24.5±1.6 min; P<0.05). The MB group had less postoperative bruising (1 case, 4.5%) than the control group (5 cases, 25%; P<0.05). The surgical results were similar in both groups, with a Lysholm score of 87.23±1.80 in the MB group and 87.23±1.62 (P>0.05) in the control group. CONCLUSIONS This study showed that preoperative injection of MB for popliteal cysts before arthroscopic debridement improved cyst localization and ease and accuracy of surgery and reduced operative time, adjacent tissue damage, postoperative complications, and recurrence rate.

A meta-analysis on the potency of foot-and-mouth disease vaccines in different animal models.

Whether mice can be used as a foot-and-mouth disease (FMD) model has been debated for a long time. However, the major histocompatibility complex between pigs and mice is very different. In this study, the protective effects of FMD vaccines in different animal models were analyzed by a meta-analysis. The databases PubMed, China Knowledge Infrastructure, EMBASE, and Baidu Academic were searched. For this purpose, we evaluated evidence from 14 studies that included 869 animals with FMD vaccines. A random effects model was used to combine effects using Review Manager 5.4 software. A forest plot showed that the protective effects in pigs were statistically non-significant from those in mice [MH = 0.56, 90% CI (0.20, 1.53), P = 0.26]. The protective effects in pigs were also statistically non-significant from those in guinea pigs [MH = 0.67, 95% CI (0.37, 1.21), P = 0.18] and suckling mice [MH = 1.70, 95% CI (0.10, 28.08), P = 0.71]. Non-inferiority test could provide a hypothesis that the models (mice, suckling mice and guinea pigs) could replace pigs as FMDV vaccine models to test the protective effect of the vaccine. Strict standard procedures should be established to promote the assumption that mice and guinea pigs should replace pigs in vaccine evaluation.

An artificial intelligence model for detecting pathological lymph node metastasis in prostate cancer using whole slide images: a retrospective, multicentre, diagnostic study.

Background: The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. Methods: In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. Findings: In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64-73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953-0.998) to 0.992 (0.982-1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908-1.000]) surpassed that of two junior pathologists (0.862 [0.746-0.939], P = 0.023; 0.879 [0.767-0.950], P = 0.041) by 10-12% and showed no difference to that of two senior pathologists (both 0.983 [0.908-1.000], both P > 0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P = 0.041) to the level of senior pathologists (both P > 0.99), and substantially reduced the four pathologists' slide reviewing time (-31%, P < 0.0001; -34%, P < 0.0001; -29%, P < 0.0001; and -27%, P = 0.00031). Interpretation: ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application. Funding: National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

A Portable Nucleic Acid Testing Platform with Photosensitization, a Three-Dimensionally Printed Multipiece Chip, and Digital Color Sensing.

Portable nucleic acid testing (NAT) holds great promise for point-of-care disease diagnosis and field-based applications but remains difficult to achieve. Herein, we describe a portable NAT that streamlines loop-mediated isothermal amplification with photosensitization-based color development in a fully sealed 3D-printed multipiece chip. Using a smartphone accessory and an APP, we also introduce a calibration-free quantification approach via digital color sensing and library matching. With these innovative approaches, our detection platform is highly accessible, allowing for rapid and sensitive NAT without requiring sophisticated instruments and well-trained personnel. The field applicability of our NAT platform was demonstrated by detecting tuberculosis infections in clinical sputum samples and food adulteration in commercial salmon meat products.

Assessment of the impact of the vaccine pass policy on COVID-19 vaccine hesitancy and uptake among Chinese adults in Hong Kong.

BACKGROUND: Recognising the importance of attaining high vaccine coverage to mitigate the COVID-19 impact, a Vaccine Pass scheme was implemented during and after the first large Omicron wave with high mortality in older ages in Hong Kong in early 2022 requiring three doses by June 2022. We did not identify any studies evaluating the policy impact of vaccination mandates with vaccine uptake over whole policy period of time in a Chinese population. We aim to evaluate the impact of the Vaccine Pass policy on COVID-19 vaccine uptake in adults in a Chinese population in Hong Kong. METHODS: We analysed patterns in vaccine uptake and hesitancy using local data from population vaccine registry and 32 cross-sectional telephone surveys conducted from October 2021 to December 2022. The association of Vaccine Pass phases with vaccine uptake was examined using logistic regression analyses, taking into account covariates including self-risk perception, perceived self-efficacy in preventing COVID-19 and trust in government in pandemic control as well as physical distancing measures and demographics. RESULTS: The uptake of primary series and third doses was positively significantly associated with the successive stages of Vaccine Pass implementation (adjusted odds ratios ranged from 2.41 to 7.81). Other statistically significant drivers of uptake included age group, chronic condition, higher perceived personal susceptibility to COVID-19, higher trust in government, and higher educational attainment. CONCLUSION: Vaccine uptake in older adults was observed to have increased by a greater extent after the policy annoucement and implementation, under the contextual changes during and after a large Omicron wave with high mortality in Hong Kong in early 2022. Since the policy withdrawal the uptake of further booster doses has been very low in all ages. We suggest that improving voluntary booster uptake in older adults should be prioritized.

MRI index of glymphatic system mediates the influence of locus coeruleus on cognition in Parkinson's disease.

INTRODUCTION: Although locus coeruleus (LC) has been demonstrated to play a critical role in the cognitive function of Parkinson's disease (PD), the underlying mechanism has not been elucidated. The objective was to investigate the relationship among LC degeneration, cognitive performance, and the glymphatic function in PD. METHODS: In this retrospective study, 71 PD subjects (21 with normal cognition; 29 with cognitive impairment (PD-MCI); 21 with dementia (PDD)) and 26 healthy controls were included. All participants underwent neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and diffusion tensor image scanning on a 3.0 T scanner. The brain glymphatic function was measured using diffusion along the perivascular space (ALPS) index, while LC degeneration was estimated using the NM contrast-to-noise ratio of LC (CNRLC). RESULTS: The ALPS index was significantly lower in both the whole PD group (P = 0.04) and the PDD subgroup (P = 0.02) when compared to the controls. Similarly, the CNRLC was lower in the whole PD group (P < 0.001) compared to the controls. In the PD group, a positive correlation was found between the ALPS index and both the Montreal Cognitive Assessment (MoCA) score (r = 0.36; P = 0.002) and CNRLC (r = 0.26; P = 0.03). Mediation analysis demonstrated that the ALPS index acted as a significant mediator between CNRLC and the MoCA score in PD subjects. CONCLUSION: The ALPS index, a neuroimaging marker of glymphatic function, serves as a mediator between LC degeneration and cognitive function in PD.

Global trends in colorectal cancer and metabolic syndrome research: a bibliometric and visualization analysis.

Numerous studies have demonstrated a robust correlation between metabolic syndrome (MetS) and colorectal cancer (CRC). Nonetheless, no systematic analysis or visualization of relevant publications has been conducted via bibliometrics. This research, centred on 616 publications obtainable through the Web of Science Core Collection (WoSCC), employed CiteSpace software and VOSviewer software for correlation analyses of authors, journals, institutions, countries, keywords, and citations. The findings indicate that the Public Library of Science had the highest number of publications, while the United States, China and South Korea were the most contributory nations. Recent years have seen the mechanisms linking Metabolic Syndrome with Colorectal Cancer, including diet, obesity, insulin resistance and intestinal flora, remain a burgeoning research area. Furthermore, bariatric surgery appears to be a promising new area of study. This paper presents the initial bibliometric and visualization analysis of research literature concerning CRC and MetS which examines research trends and hotspots.

Comparative epidemiology of outbreaks caused by SARS-CoV-2 Delta and Omicron variants in China.

From 2020 to December 2022, China implemented strict measures to contain the spread of severe acute respiratory syndrome coronavirus 2. However, despite these efforts, sustained outbreaks of the Omicron variants occurred in 2022. We extracted COVID-19 case numbers from May 2021 to October 2022 to identify outbreaks of the Delta and Omicron variants in all provinces of mainland China. We found that omicron outbreaks were more frequent (4.3 vs. 1.6 outbreaks per month) and longer-lasting (mean duration: 13 vs. 4 weeks per outbreak) than Delta outbreaks, resulting in a total of 865,100 cases, of which 85% were asymptomatic. Despite the average Government Response Index being 12% higher (95% confidence interval (CI): 9%, 15%) in Omicron outbreaks, the average daily effective reproduction number (Rt) was 0.45 higher (95% CI: 0.38, 0.52, p < 0.001) than in Delta outbreaks. Omicron outbreaks were suppressed in 32 days on average (95% CI: 26, 39), which was substantially longer than Delta outbreaks (14 days; 95% CI: 11, 19; p = 0.004). We concluded that control measures effective against Delta could not contain Omicron outbreaks in China. This highlights the need for continuous evaluation of new variants' epidemiology to inform COVID-19 response decisions.

A two-step method preparation of semaglutide through solid-phase synthesis and inclusion body expression.

Semaglutide is currently the most promising antidiabetic drug, especially for the treatment of type 2 diabetes mellitus, due to its excellent efficacy in glycemic control and weight loss. However, the production of semaglutide remains high cost, and high yield, low cost, and high purity still remains a challenge. Herein, we reported a convenient and high-yield strategy for the preparation of semaglutide through fragmented condensation coupling, involving solid-phase peptide synthesis of tetrapeptide and on-column refolding and on-column enzyme cleavage based inclusion body expression of Lys26Arg34GLP-1 (11-37) with fused protein tags in an X-Y-D4K-G pattern. The optimized N-terminal protein tag significantly boosts inclusion body expression level, while on-column refolding and on-column enzyme cleavage avoid precipitation, enhancing efficiency and yield together with one-step purification. The successful preparation of semaglutide is expected to achieve large-scale industrial production with low cost, high yield and high purity.