Rational molecular design converting fascaplysin derivatives to potent broad-spectrum inhibitors against bacterial pathogens via targeting FtsZ.

The filamentous temperature-sensitive mutant Z protein (FtsZ), a key player in bacterial cell division machinery, emerges as an attractive target to tackle the plight posed by the ever growing antibiotic resistance over the world. Therefore in this regard, agents with scaffold diversities and broad-spectrum antibacterial activity against Gram-positive and Gram-negative pathogens are highly needed. In this study, a new class of marine-derived fascaplysin derivatives has been designed and synthesized by Suzuki-Miyaura cross-coupling. Some compounds exhibited potent bactericidal activities against a panel of Gram-positive (MIC = 0.024-6.25 µg/mL) and Gram-negative (MIC = 1.56-12.5 µg/mL) bacteria including methicillin-resistant S. aureus (MRSA). They exerted their effects by dual action mechanism via disrupting the integrity of the bacterial cell membrane and targeting FtsZ protein. These compounds stimulated polymerization of FtsZ monomers and bundling of the polymers, and stabilized the resulting polymer network, thus leading to the dysfunction of FtsZ in cell division. In addition, these agents showed negligible hemolytic activity and low cytotoxicity to mammalian cells. The studies on docking and molecular dynamics simulations suggest that these inhibitors bind to the hydrophilic inter-domain cleft of FtsZ protein and the insights obtained in this study would facilitate the development of potential drugs with broad-spectrum bioactivities.

Genetically predicted gut microbiome and risk of oral cancer.

PURPOSE: Mounting evidence suggests a possible link between gut microbiome and oral cancer, pointing to some potential modifiable targets for disease prevention. In the present study, Mendelian randomization (MR) was used to explore whether there was a causal link between gut microbiome and oral cancer. METHODS: The single nucleotide polymorphisms (SNPs) significantly associated with gut microbiome were served as instrumental variables. MR analyses were performed using genetic approaches such as inverse variance weighting (IVW), MR Egger and weighted median, with IVW as the primary approach, supplemented by MR Egger and weighted median. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were used to detect the presence of horizontal pleiotropy and identify outlier SNPs. RESULTS: Causal effect estimates indicated that genetically predicted abundance of Prevotellaceae was associated with higher risk of oral cancer (odds ratio (OR) 1.80, 95% confidence interval (CI) 1.16-2.81, p = 0.009). There was no evidence of notable heterogeneity and horizontal pleiotropy. CONCLUSION: Genetically derived estimates suggest that Prevotellaceae may be associated with the risk of oral cancer. Such robust evidence should be given priority in future studies and explore the underlying mechanisms.

A Single-Enantiomer Emitter Enabled Superstructural Helix Inversion for Upconverting and Downshifting Luminescence with Bidirectional Circular Polarization.

The helical twisting tendency of liquid crystals (LCs) is generally governed by the inherent configuration of the chiral emitter. Here, we introduce the multistage inversion of supramolecular chirality as well as circularly polarized luminescence (CPL) by manipulating the ratio of single enantiomeric emitters (R-PCP) to LC monomers (5CB). Increasing the content of R-PCP from 1 wt % to 3 wt % inverted the helix of LCs from left-handed to right-handed, accompanying a CPL sign changed from positive to negative. The biaxiality of chiral emitters, as well as the steric effect of chiral-chiral and chiral-achiral interaction, were identified as the reasons for helical sense inversion. Due to the strong helical twisting power, 4 wt % R-PCP drove the photonic band gap (PBG) of chiral LCs to match up with their emission range, leading to an inversion of the CPL again with a high dissymmetry factor (≈1.2). Directly adjusting the PBG using chiral emitters is seldom achieved in cholesteric LCs. On this basis, an achiral sensitizer PtTPBP was assembled into the helical superstructure. The generation of triplet-triplet annihilation-induced upconverted CPL from R-PCP and the downshifting CPL from PtTPBP with opposite rotation was achieved in a single chiral LC system by tuning the position of the PBG.

Improvement of triterpenoid production in mycelia of Antrodia camphorata through mutagenesis breeding and amelioration of CCl4-induced liver injury in mice.

Due to the scarcity of wild fruiting bodies, submerged fermentation of the medicinal fungus Antrodia camphorata is attracting much attention, but the production of bioactive triterpenoids is low. Therefore, there is an urgent need to improve the triterpenoid yield of submerged fermentation. Here, the A. camphorata mutant E3-64 was generated from strain AC16101 through random mutagenesis breeding, producing 172.8 mg triterpenoid per gram of dry mycelia. Further optimization of culture parameters resulted in a yield of 255.5 mg/g dry mycelia (i.e., an additional >1.4-fold increase), which is the highest reported yield thus far. Notably, mutant E3-64 produced 94% and 178% more of the triterpenoid components antcin A and antcamphin A, respectively, while it produced 52% and 15% less antcin B and G, respectively. Mutant E3-64 showed increased expression of key genes involved in triterpenoid biosynthesis, as well as different genome-wide single-nucleotide polymorphisms as compared with AC16101. Triterpenoids of the E3-64 mycelia exhibited remarkably protective activity against acute CCl4-induced liver injury in mice. This study shows the potential of A. camphorata for scientific research and commercial application.

Recyclable soft photonic crystal film with overall improved circularly polarized luminescence.

Existing circularly polarized luminescence materials can hardly satisfy the requirements of both large luminescence dissymmetry factor and high luminescent quantum yield, which hinders their practical applications. Here, we present a soft photonic crystal film embedded with chiral nanopores that possesses excellent circularly polarized luminescence performance with a high luminescence dissymmetry factor as well as a large luminescent quantum yield when loaded with various luminescent dyes. Benefitting from the retention of chiral nanopores imprinted from a chiral liquid crystal arrangement, the chiral soft photonic crystal film can not only endow dyes with chiral properties, but also effectively avoid severe aggregation of guest dye molecules. More importantly, the soft photonic crystal film can be recycled many times by loading and eluting guest dye molecules while retaining good stability as well as circularly polarized luminescence performance, enabling various applications, including smart windows, multi-color circularly polarized luminescence and anticounterfeiting.

IL-10-dependent Effect of Chinese Medicine Abelmoschus manihot on Alleviating Intestinal Inflammation and Modulating Gut Microbiota.

Inflammatory bowel disease (IBD) is a recurrent disease associated with a potential risk of colorectal cancer. Abelmoschus manihot (AM), a Chinese herbal medicine, is known to alleviate IBD. However, its mechanism of action requires further clarification. Here, we focused on the role of IL-10 and the gut microbiota in the mechanism of action of AM. The effects of AM on intestinal inflammation, mucus production, and gut microbes were evaluated in dextran sodium sulfate (DSS)-induced acute and chronic IBD models and in IL-10-deficient mice (IL-10[Formula: see text]). AM exhibited protective effects on acute and chronic models of IBD in wild-type mice by restoring body weight and colon length, promoting IL-10 secretion, and decreasing TNF-[Formula: see text] levels. Moreover, AM alleviated inflammatory infiltration, increased mucin 2 transcription, and increased the number of goblet cells in the colon. On the contrary, these effects were diminished in IL-10[Formula: see text] mice, which implied that the effect of AM on intestinal inflammation is IL-10-dependent. A gut microbial sequencing analysis showed that gut microbial dysbiosis was modulated by AM intervention. The regulatory effects of AM on Eggerthellaceae, Sutterellaceae, Erysipelotrichaceae, Burkholderiaceae, Desulfovibrionaceae, and Enterococcaceae were dependent on IL-10. These results revealed that AM ameliorated IBD and modulated gut microbes by promoting IL-10 secretion, indicating that AM has the potential to improve IBD and that AM is IL-10-dependent.

DROID: Driver-Centric Risk Object Identification.

Identification of high-risk driving situations is generally approached through collision risk estimation or accident pattern recognition. In this work, we approach the problem from the perspective of subjective risk. We operationalize subjective risk assessment by predicting driver behavior changes and identifying the cause of changes. To this end, we introduce a new task called driver-centric risk object identification (DROID), which uses egocentric video to identify object(s) influencing a driver's behavior, given only the driver's response as the supervision signal. We formulate the task as a cause-effect problem and present a novel two-stage DROID framework, taking inspiration from models of situation awareness and causal inference. A subset of data constructed from the Honda Research Institute Driving Dataset (HDD) is used to evaluate DROID. We demonstrate state-of-the-art DROID performance, even compared with strong baseline models using this dataset. Additionally, we conduct extensive ablative studies to justify our design choices. Moreover, we demonstrate the applicability of DROID for risk assessment.

Discovery of Itaconate-Mediated Lysine Acylation.

Itaconate is an important antimicrobial and immunoregulatory metabolite involved in host-pathogen interactions. A key mechanistic action of itaconate is through the covalent modification of cysteine residues via Michael addition, resulting in "itaconation". However, it is unclear whether itaconate has other regulatory mechanisms. In this work, we discovered a novel type of post-translational modification by promiscuous antibody enrichment and data analysis with the open-search strategy and further confirmed it as the lysine "itaconylation". We showed that itaconylation and its precursor metabolite itaconyl-CoA undergo significant upregulation upon lipopolysaccharides (LPS) stimulation in RAW264.7 macrophages. Quantitative proteomics identified itaconylation sites in multiple functional proteins, including glycolytic enzymes and histones, some of which were confirmed by synthetic peptide standards. The discovery of lysine itaconylation opens up new areas for studying how itaconate participates in immunoregulation via protein post-translational modification.

Cascade energy transfer boosted near-infrared circularly polarized luminescence of nanofibers from an exclusively achiral system.

We constructed chiral supramolecular nanofibers for light harvesting based on symmetry-breaking, and these can generate near-infrared circularly polarized luminescence (CPL) with high dissymmetry factor (glum) through a synergistic energy transfer and chirality transfer process. Firstly, the achiral molecule BTABA was assembled into a symmetry-breaking assembly using a seeded vortex strategy. Subsequently, the chiral assembly can endow the two achiral acceptors, Nile Red (NR) and Cyanine 7 (CY7), with supramolecular chirality, as well as chiroptical properties. CY7 can reach an excited state and emit near-infrared light through a cascade energy transfer process from BTABA to NR and then to CY7, but cannot directly acquire energy from the excited BTABA. Significantly, the near-infrared CPL of CY7 can be obtained with a boosted glum value of 0.03. This work will provide a deep insight into the preparation of materials with near-infrared CPL activity from an exclusively achiral system.

Root canal treatment of type â ¡ and â ¢A double dens invaginatus in maxillary lateral incisor: a case report.

Dens invaginatus is a rare developmental anomaly of the teeth that is caused by the infolding of enamel organs or the penetration of their proliferations into dental papillae before calcification has occurred. The presence of double dens invaginatus is extremely rare. This paper describes the use of cone beam computed tomography in the evaluation of a maxillary lateral incisor with double dens invaginatus and periapical periodontitis. The tooth was treated through microscopic root canal therapy. The tooth was free of clinical symptoms, and the periradicular lesion narrowed during the follow-up period of 1 year.

Cupric ions inducing dynamic hormesis in duckweed systems for swine wastewater treatment: Quantification, modelling and mechanisms.

Hormesis has attracted close attention of environmental and toxicological communities over the past decades. Most studies focused on the hormesis induced by stressors in the aspect of their biotoxicity to organisms, while little research was conducted on hormesis in the aspect of biological wastewater treatment process. In this study, removal of NH4+-N and Cu2+ by S. polyrrhiza under long-term Cu2+ exposure at environmentally relevant concentrations in swine wastewater was investigated. Removal efficiencies of NH4+-N by duckweeds at 0.0, 0.1, 0.5, 1.0, 2.0 and 4.0 mg/L Cu2+ were 81.6 %, 83.7 %, 89.4 %, 74.9 %, 61.8 % and 45.1 % on day 28, however, during the initial period of cultivation (0-4 days), such hormetic effect was not observed, indicating time-dependent feature of hormesis in NH4+-N removal. The modified logistic growth model was applied to describe long-term hormesis induced by Cu2+ on NH4+-N removal and it suggested that the optimal copper exposure for ammonium removal was 0.48 mg/L. More importantly, it was found that previous exposure to low doses of Cu2+ (0-1 mg/L) could enhance NH4+-N removal performance under the second exposure. Cu2+ above 1 mg/L could switch copper bioaccumulation pattern from the Langmiur-irreversible type to reversible one, indicating risk of secondary pollution. Six components including freshly-produced humic-like substances, lignin, fulvic acid-protein complex, free amino acid-like substances, tyrosine-like substance and soluble amino acid-like substances in duckweeds were detected by parallel factor (PARAFAC) model detected. Principle component analysis (PCA) conducted on PARAFAC components suggested that enhanced synthesis of protein and growth factors intracellularly at low dose stimulation improved ammonia uptake from the environment. This study provided a novel strategy to improve treatment performance of duckweeds for copper contaminated wastewater and helped understand biochemical responses and their roles in evolutionary adaptive strategies to stresses.

Using natural language processing to identify opioid use disorder in electronic health record data.

BACKGROUND: As opioid prescriptions have risen, there has also been an increase in opioid use disorder (OUD) and its adverse outcomes. Accurate and complete epidemiologic surveillance of OUD, to inform prevention strategies, presents challenges. The objective of this study was to ascertain prevalence of OUD using two methods to identify OUD in electronic health records (EHR): applying natural language processing (NLP) for text mining of unstructured clinical notes and using ICD-10-CM diagnostic codes. METHODS: Data were drawn from EHR records for hospital and emergency department patient visits to a large regional academic medical center from 2017 to 2019. International Classification of Disease, 10th Edition, Clinic Modification (ICD-10-CM) discharge codes were extracted for each visit. To develop the rule-based NLP algorithm, a stepwise process was used. First, a small sample of visits from 2017 was used to develop initial dictionaries. Next, EHR corresponding to 30,124 visits from 2018 were used to develop and evaluate the rule-based algorithm. A random sample of the results were manually reviewed to identify and address shortcomings in the algorithm, and to estimate sensitivity and specificity of the two methods of ascertainment. Last, the final algorithm was then applied to 29,212 visits from 2019 to estimate OUD prevalence. RESULTS: While there was substantial overlap in the identified records (n = 1,381 [59.2 %]), overall n = 2,332 unique visits were identified. Of the total unique visits, 430 (18.4 %) were identified only by ICD-10-CM codes, and 521 (22.3 %) were identified only by NLP. The prevalence of visits with evidence of an OUD diagnosis in this sample, ascertained using only ICD-10-CM codes, was 1,811/29,212 (6.1 %). Including the additional 521 visits identified only by NLP, the estimated prevalence of OUD is 2,332/29,212 (7.9 %), an increase of 29.5 % compared to the use of ICD-10-CM codes alone. The estimated sensitivity and specificity of the NLP-based OUD classification were 81.8 % and 97.5 %, respectively, relative to gold-standard manual review by an expert addiction medicine physician. CONCLUSION: NLP-based algorithms can automate data extraction and identify evidence of opioid use disorder from unstructured electronic healthcare records. The most complete ascertainment of OUD in EHR was combined NLP with ICD-10-CM codes. NLP should be considered for epidemiological studies involving EHR data.

Berbamine Hydrochloride inhibits lysosomal acidification by activating Nox2 to potentiate chemotherapy-induced apoptosis via the ROS-MAPK pathway in human lung carcinoma cells.

Autophagy is typically activated in cancer cells as a rescue strategy in response to cellular stress (e.g., chemotherapy). Herein, we found that Berbamine Hydrochloride (Ber) can act as an effective inhibitor of the late stage of autophagic flux, thereby potentiating the killing effect of chemotherapy agents. Lung carcinoma cells exposed to Ber exhibited increased autophagosomes, marked by LC3-II upregulation. The increased level of p62 after Ber treatment indicated that the autophagic flux was blocked at the late stage. The lysosome staining assay and cathepsin maturation detection indicated impaired lysosomal acidification. We found that Nox2 exhibited intensified co-localization with lysosomes in Ber-treated cells. Nox2 is a key enzyme for superoxide anion production capable of transferring electrons into the lysosomal lumen, thereby neutralizing the inner protons; this might explain the aberrant acidification. This hypothesis is further supported by the observed reversal of lysosomal cathepsin maturation by Nox2 inhibitors. Finally, Ber combined with cisplatin exhibited a synergistic killing effect on lung carcinoma cells. Further data suggested that lung carcinoma cells co-treated with Ber and cisplatin accumulated excessive reactive oxygen species (ROS), which typically activated MAPK-mediated mitochondria-dependent apoptosis. The enhanced anti-cancer effect of Ber combined with cisplatin was also confirmed in an in vivo xenograft mouse model. These findings indicate that Ber might be a promising adjuvant for enhancing the cancer cell killing effect of chemotherapy via the inhibition of autophagy. In this process, Nox2 might be a significant mediator of Ber-induced aberrant lysosomal acidification.

Machine Learning Guides Peptide Nucleic Acid Flow Synthesis and Sequence Design.

Peptide nucleic acids (PNAs) are potential antisense therapies for genetic, acquired, and viral diseases. Efficiently selecting candidate PNA sequences for synthesis and evaluation from a genome containing hundreds to thousands of options can be challenging. To facilitate this process, this work leverages machine learning (ML) algorithms and automated synthesis technology to predict PNA synthesis efficiency and guide rational PNA sequence design. The training data is collected from individual fluorenylmethyloxycarbonyl (Fmoc) deprotection reactions performed on a fully automated PNA synthesizer. The optimized ML model allows for 93% prediction accuracy and 0.97 Pearson's r. The predicted synthesis scores are validated to be correlated with the experimental high-performance liquid chromatography (HPLC) crude purities (correlation coefficient R2 = 0.95). Furthermore, a general applicability of ML is demonstrated through designing synthetically accessible antisense PNA sequences from 102 315 predicted candidates targeting exon 44 of the human dystrophin gene, SARS-CoV-2, HIV, as well as selected genes associated with cardiovascular diseases, type II diabetes, and various cancers. Collectively, ML provides an accurate prediction of PNA synthesis quality and serves as a useful computational tool for informing PNA sequence design.

Antibiotic-induced depletion of Clostridium species increases the risk of secondary fungal infections in preterm infants.

Preterm infants or those with low birth weight are highly susceptible to invasive fungal disease (IFD) and other microbial or viral infection due to immaturity of their immune system. Antibiotics are routinely administered in these vulnerable infants in treatment of sepsis and other infectious diseases, which might cause perturbation of gut microbiome and hence development of IFD. In this study, we compared clinical characteristics of fungal infection after antibiotic treatment in preterm infants. As determined by 16S rRNA sequencing, compared with non-IFD patients with or without antibiotics treatment, Clostridium species in the intestinal tracts of patients with IFD were almost completely eliminated, and Enterococcus were increased. We established a rat model of IFD by intraperitoneal inoculation of C. albicans in rats pretreated with meropenem and vancomycin. After pretreatment with antibiotics, the intestinal microbiomes of rats infected with C. albicans were disordered, as characterized by an increase of proinflammatory conditional pathogens and a sharp decrease of Clostridium species and Bacteroides. Immunofluorescence analysis showed that C. albicans-infected rats pretreated with antibiotics were deficient in IgA and IL10, while the number of Pro-inflammatory CD11c+ macrophages was increased. In conclusion, excessive use of antibiotics promoted the imbalance of intestinal microbiome, especially sharp decreases of short-chain fatty acids (SCFA)-producing Clostridium species, which exacerbated the symptoms of IFD, potentially through decreased mucosal immunomodulatory molecules. Our results suggest that inappropriate use of broad-spectrum antibiotics may promote the colonization of invasive fungi. The results of this study provide new insights into the prevention of IFD in preterm infants.

Requirement of a putative mitochondrial GTPase, GemA, for azole susceptibility, virulence, and cell wall integrity in Aspergillus fumigatus.

Drug resistance in fungal pathogens is a new challenge in clinical aspergillosis treatment. Mitochondria as dynamic organelles are involved in numerous biological processes in fungi, including drug resistance. However, little is known about the mechanism underlying mitochondrial regulation of the response of fungal pathogens to antifungal drugs. Here, we showed that a putative mitochondrial GTPase, GemA, a yeast Gem1 homolog, is crucial for the azole response and cell wall integrity in the opportunistic pathogen Aspergillus fumigatus. The fluorescence observation showed that GFP-labeled GemA is located in mitochondria, and loss of gemA results in aberrant giant mitochondrial morphology and abnormal mitochondrial membrane potential. Moreover, a ΔgemA mutant attenuates fungal virulence in the Galleria mellonella model of aspergillosis. Furthermore, gemA loss increases resistance to azoles and terbinafine but not to amphotericin B. Of note, RNA-seq combined with RT-qPCR showed that a series of drug efflux pumps were upregulated in the gemA deletion mutant. Deleting mdr1 or inhibiting the expression of drug efflux pumps can partially decrease the resistance to azoles resulting from the gemA mutant, implying that GemA influences azole response by affecting the expression of drug efflux pumps. Importantly, the ΔgemA mutant is susceptible to the cell wall-perturbing reagent CR, but not to CFW, and this defect can be partly rescued by hyperosmotic stress. TEM revealed that the cell wall of ΔgemA was thicker than that of the WT strain, demonstrating that GemA plays a role in cell wall composition and integrity. Collectively, we identified a putative mitochondrial GTPase, GemA, which is critical for hyphal growth, virulence, azole susceptibility, and cell wall integrity and acts by affecting mitochondrial function.

Single-cell transcriptomics reveals the natural product Shi-Bi-Man promotes hair regeneration by activating the FGF pathway in dermal papilla cells.

BACKGROUND: Finasteride and minoxidil are two commonly used drugs for the treatment of hair loss. However, these two drugs have certain side effects. Thus, the further elucidation of treatments for hair loss, including those using Chinese herbal medicine, remains important clinically. Shi-Bi-Man (SBM) is a hair health supplement that darkens hair and contains ginseng radix, tea polyphenols, polygonum multiflorum, radix angelicae sinensis, aloe, linseed, and green tea extract. PURPOSE: This study aimed to find potential effective monomer components to promote hair regeneration from SBM and to explore the mechanism of SBM to promote hair regeneration. METHODS: Supplementation with the intragastric administration or smear administration of SBM in artificially shaved C57BL/6 mice, observe its hair growth. UPLC/MS and UPLC/LTQ-Orbitrap-MS detect the main components in SBM and the main monomers contained in the skin after smearing, respectively. A network pharmacology study on the main components of SBM and single-cell RNA sequencing was performed to explore the role of SBM for hair regeneration. RESULTS: SBM significantly induced hair growth compared with a control treatment. TSG and EGCG were the main monomers in the skin after SBM smearing. The results of single-cell sequencing revealed that after SBM treatment, the number of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) increased significantly. Cell interactions and volcano dots show that the interaction of the FGF signaling pathway was significantly enhanced, in which Fgf7 expression was especially upregulated in DPCs. In addition, the Wnt signaling pathway also had a partially enhanced effect on the interactions between various cells in the skin. The network pharmacology study showed that the promotion of the FGF and Wnt pathways by SBM was also enriched in alopecia diseases. CONCLUSION: We report that SBM has a potential effect on the promotion of hair growth by mainly activating the FGF signaling pathway. The use of SBM may be a novel therapeutic option for hair loss.

Maternal exposure to cadmium from puberty through lactation induces abnormal reproductive development in female offspring.

Four-week-old female ICR mice were exposed to Cd through drinking water from puberty through lactation to investigate the effects of reproductive development in female offspring. Our results showed that maternal Cd exposure from puberty to lactation induced vaginal opening delay, and disturbed estrous cycle in the offspring on postnatal day (PND) 21, without affecting the body weight at vaginal opening. The histopathology results showed the increased primordial follicles and the decreased secondary follicles, and the mRNA level of Amh increased in the offspring's ovaries upon Cd exposure, suggesting the inhibition of ovarian follicular development on PND21. Moreover, the level of serum estradiol reduced and genes associated with steroidogenesis (3ß-Hsd, P450scc and P450arom) were downregulated upon Cd exposure on PND 21. Thus, Cd may inhibit the follicular development via disturbing the mRNA level of genes associated with steroidogenesis and then the synthesis of estradiol in prepuberty. Taken together, despite the lack of attention to estrous cycle at termination, maternal Cd exposure from puberty to lactation induced the adverse effects on reproductive development of female offspring, including the delay of vaginal opening, irregular estrous cycle and inhibition of follicular development, via disturbing the mRNA level of genes associated with follicular development and steroidogenesis.

Homologous and Heterologous Chiral Supramolecular Polymerization from Exclusively Achiral Building Blocks.

Among the enticing issues of chiral origins are: how chirality is born from the initial achiral units and the mechanisms for the transfer of chiral information. In this work, by combining a physical vortex and chiral seeds, a general process is revealed to generate chiral supramolecular polymers from achiral C3 -symmetric molecules. The symmetry-broken assemblies from the achiral molecules could work as chiral seeds to initiate the polymerization of either homologous or heterologous achiral monomers. Concomitantly, the fragmentation of the polymer caused by the vortex during the nucleation-elongation stages is shown to enlarge the domains of the chiral nuclei and then guide the polymer to grow into the predominant helicity with a high reactivity ratio. Moreover, the chiral structural information can be stored in different forms of assemblies. These new polymerization modes will provide guidance for the preparation of chiral materials.

[Discussion on the essential thought of Ma's warm moxibustion technique for "unblocking fu-organs"].

"Unblocking fu organs" is one of the essential principles of Ma's warm moxibustion technique, characterized as "dredging" and "harmonizing" for either deficiency or excess condition. Under the guidance of this therapeutic thought, the acupoints for moxibustion are mainly selected from the middle and lower parts of the body. Regarding the therapeutic approach, the acupoint prescription for moxibustion should be formed in line with warming and promoting circulation of fu organs; the moxibustion degree should be specially considered, in which, the mild moxibustion is recommended to induce promoting action; and the systematic moxibustion technique should be the root for dredging fu organs and regulating zang organs. Ma's mild moxibustion technique stresses on removing the obstruction of fu organs and emphasizes promoting the qi activity of sanjiao (triple energizer) and regulating the balance of five zang organs.