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The paper summarizes the clinical experience of professor ZHANG Ren in the staging treatment with characteristic acupuncture techniques for oculomotor paralysis. According to the symptoms of oculomotor paralysis, the staging treatment is given, in which acupuncture is dominant and the needling techniques are optioned in compliance with the symptoms. In the early, middle and late stages of illness, three different acupuncture therapies are delivered accordingly, i.e. the combination of the point-toward-point needling at the four acupoints located on the forehead and the electroacupuncture with disperse-dense wave, the surrounding needling and the triple needling at the acupoints around the eyeball, as well as the perpendicular needle insertion at the three acupoints within the orbit. Professor ZHANG Ren lays the stress on identifying the etiology and differentiating the symptoms, as well as the early intervention for the disease. For the intractable cases, the comprehensive regimen such as acupoint injection, dermal needling and auricular point sticking is supplemented. During treatment, the spirit harmonization is greatly considered to ensure the effectiveness. On the basis of the staging acupuncture therapy, the acupuncture technique for harmonizing the spirit and regulating qi is combined to obtain the favorable clinical effect on oculomotor paralysis.

The membrane-cytoplasmic linker defines activity of FtsH proteases in Pseudomonas aeruginosa clone C.

Pandemic Pseudomonas aeruginosa clone C strains encode two inner-membrane associated ATP-dependent FtsH proteases. PaftsH1 is located on the core genome and supports cell growth and intrinsic antibiotic resistance, whereas PaftsH2, a xenolog acquired through horizontal gene transfer from a distantly related species, is unable to functionally replace PaftsH1. We show that purified PaFtsH2 degrades fewer substrates than PaFtsH1. Replacing the 31-amino acid-extended linker region of PaFtsH2 spanning from the C-terminal end of the transmembrane helix-2 to the first seven highly divergent residues of the cytosolic AAA+ ATPase module with the corresponding region of PaFtsH1 improves hybrid-enzyme substrate processing in vitro and enables PaFtsH2 to substitute for PaFtsH1 in vivo. Electron microscopy indicates that the identity of this linker sequence influences FtsH flexibility. We find membrane-cytoplasmic (MC) linker regions of PaFtsH1 characteristically glycine-rich compared to those from FtsH2. Consequently, introducing three glycines into the membrane-proximal end of PaFtsH2's MC linker is sufficient to elevate its activity in vitro and in vivo. Our findings establish that the efficiency of substrate processing by the two PaFtsH isoforms depends on MC linker identity and suggest that greater linker flexibility and/or length allows FtsH to degrade a wider spectrum of substrates. As PaFtsH2 homologs occur across bacterial phyla, we hypothesize that FtsH2 is a latent enzyme but may recognize specific substrates or is activated in specific contexts or biological niches. The identity of such linkers might thus play a more determinative role in the functionality of and physiological impact by FtsH proteases than previously thought.

Evolution of cyclic di-GMP signalling on a short and long term time scale.

Diversifying radiation of domain families within specific lineages of life indicates the importance of their functionality for the organisms. The foundation for the diversifying radiation of the cyclic di-GMP signalling network that occurred within the bacterial kingdom is most likely based in the outmost adaptability, flexibility and plasticity of the system. Integrative sensing of multiple diverse extra- and intracellular signals is made possible by the N-terminal sensory domains of the modular cyclic di-GMP turnover proteins, mutations in the protein scaffolds and subsequent signal reception by diverse receptors, which eventually rewires opposite host-associated as well as environmental life styles including parallel regulated target outputs. Natural, laboratory and microcosm derived microbial variants often with an altered multicellular biofilm behaviour as reading output demonstrated single amino acid substitutions to substantially alter catalytic activity including substrate specificity. Truncations and domain swapping of cyclic di-GMP signalling genes and horizontal gene transfer suggest rewiring of the network. Presence of cyclic di-GMP signalling genes on horizontally transferable elements in particular observed in extreme acidophilic bacteria indicates that cyclic di-GMP signalling and biofilm components are under selective pressure in these types of environments. On a short and long term evolutionary scale, within a species and in families within bacterial orders, respectively, the cyclic di-GMP signalling network can also rapidly disappear. To investigate variability of the cyclic di-GMP signalling system on various levels will give clues about evolutionary forces and discover novel physiological and metabolic pathways affected by this intriguing second messenger signalling system.

Regulation of biofilm formation in Zymomonas mobilis to enhance stress tolerance by heterologous expression of pfs and luxS.

Zymomonas mobilis is a potential alternative of Saccharomyces cerevisiae to produce cellulosic ethanol with strengths in cofactor balance, but its lower tolerance to inhibitors in the lignocellulosic hydrolysate restricts the application. Although biofilm can improve bacteria stress tolerance, regulating biofilm formation in Z. mobilis is still a challenge. In this work, we constructed a pathway by heterologous expressing pfs and luxS from Escherichia coli in Z. mobilis to produce AI-2 (autoinducer 2), a universal quorum-sensing signal molecule, to control cell morphology for enhancing stress tolerance. Unexpectedly, the results suggested that neither endogenous AI-2 nor exogenous AI-2 promoted biofilm formation, while heterologous expression of pfs can significantly raise biofilm. Therefore, we proposed that the main factor in assisting biofilm formation was the product accumulated due to heterologous expression of pfs, like methylated DNA. Consequently, ZM4::pfs produced more biofilm, which presented an enhanced tolerance to acetic acid. All these findings provide a novel strategy to improve the stress tolerance of Z. mobilis by enhancing biofilm formation for efficient production of lignocellulosic ethanol and other value-added chemical products.

Mathematical modeling of mutated COVID-19 transmission with quarantine, isolation and vaccination.

Multiple variants of SARS-CoV-2 have emerged but the effectiveness of existing COVID-19 vaccines against variants has been reduced, which bring new challenges to the control and mitigation of the COVID-19 pandemic. In this paper, a mathematical model for mutated COVID-19 with quarantine, isolation and vaccination is developed for studying current pandemic transmission. The basic reproduction number $ \mathscr{R}_{0} $ is obtained. It is proved that the disease free equilibrium is globally asymptotically stable if $ \mathscr{R}_{0} < 1 $ and unstable if $ \mathscr{R}_{0} > 1 $. And numerical simulations are carried out to illustrate our main results. The COVID-19 pandemic mainly caused by Delta variant in South Korea is analyzed by using this model and the unknown parameters are estimated by fitting to real data. The epidemic situation is predicted, and the prediction result is basically consistent with the actual data. Finally, we investigate several critical model parameters to access the impact of quarantine and vaccination on the control of COVID-19, including quarantine rate, quarantine effectiveness, vaccination rate, vaccine efficacy and rate of immunity loss.

Patatin-like phospholipase CapV in Escherichia coli - morphological and physiological effects of one amino acid substitution.

In rod-shaped bacteria, morphological plasticity occurs in response to stress, which blocks cell division to promote filamentation. We demonstrate here that overexpression of the patatin-like phospholipase variant CapVQ329R, but not CapV, causes pronounced sulA-independent pyridoxine-inhibited cell filamentation in the Escherichia coli K-12-derivative MG1655 associated with restriction of flagella production and swimming motility. Conserved amino acids in canonical patatin-like phospholipase A motifs, but not the nucleophilic serine, are required to mediate CapVQ329R phenotypes. Furthermore, CapVQ329R production substantially alters the lipidome and colony morphotype including rdar biofilm formation with modulation of the production of the biofilm activator CsgD, and affects additional bacterial traits such as the efficiency of phage infection and antimicrobial susceptibility. Moreover, genetically diverse commensal and pathogenic E. coli strains and Salmonella typhimurium responded with cell filamentation and modulation in colony morphotype formation to CapVQ329R expression. In conclusion, this work identifies the CapV variant CapVQ329R as a pleiotropic regulator, emphasizes a scaffold function for patatin-like phospholipases, and highlights the impact of the substitution of a single conserved amino acid for protein functionality and alteration of host physiology.

Deciphering Molecular Mechanism Underlying Self-Flocculation of Zymomonas mobilis for Robust Production.

Zymomonas mobilis metabolizes sugar anaerobically through the Entner-Doudoroff pathway with less ATP generated for lower biomass accumulation to direct more sugar for product formation with improved yield, making it a suitable host to be engineered as microbial cell factories for producing bulk commodities with major costs from feedstock consumption. Self-flocculation of the bacterial cells presents many advantages, such as enhanced tolerance to environmental stresses, a prerequisite for achieving high product titers by using concentrated substrates. ZM401, a self-flocculating mutant developed from ZM4, the unicellular model strain of Z. mobilis, was employed in this work to explore the molecular mechanism underlying this self-flocculating phenotype. Comparative studies between ZM401 and ZM4 indicate that a frameshift caused by a single nucleotide deletion in the poly-T tract of ZMO1082 fused the putative gene with the open reading frame of ZMO1083, encoding the catalytic subunit BcsA of the bacterial cellulose synthase to catalyze cellulose biosynthesis. Furthermore, the single nucleotide polymorphism mutation in the open reading frame of ZMO1055, encoding a bifunctional GGDEF-EAL protein with apparent diguanylate cyclase/phosphodiesterase activities, resulted in the Ala526Val substitution, which consequently compromised in vivo specific phosphodiesterase activity for the degradation of cyclic diguanylic acid, leading to intracellular accumulation of the signaling molecule to activate cellulose biosynthesis. These discoveries are significant for engineering other unicellular strains from Z. mobilis with the self-flocculating phenotype for robust production. IMPORTANCE Stress tolerance is a prerequisite for microbial cell factories to be robust in production, particularly for biorefinery of lignocellulosic biomass to produce biofuels, bioenergy, and bio-based chemicals for sustainable socioeconomic development, since various inhibitors are released during the pretreatment to destroy the recalcitrant lignin-carbohydrate complex for sugar production through enzymatic hydrolysis of the cellulose component, and their detoxification is too costly for producing bulk commodities. Although tolerance to individual stress has been intensively studied, the progress seems less significant since microbial cells are inevitably suffering from multiple stresses simultaneously under production conditions. When self-flocculating, microbial cells are more tolerant to multiple stresses through the general stress response due to enhanced quorum sensing associated with the morphological change for physiological and metabolic advantages. Therefore, elucidation of the molecular mechanism underlying such a self-flocculating phenotype is significant for engineering microbial cells with the unique multicellular morphology through rational design to boost their production performance.

[Efficacy and mechanism of electroacupuncture on insulin resistant polycystic ovary syndrome].

OBJECTIVE: To explore the therapeutic effect and partial mechanism of electroacupuncture (EA) for patients with insulin resistance (IR) polycystic ovary syndrome (PCOS). METHODS: Seventy patients with IR-PCOS were randomly divided into an EA group (36 cases, 5 cases dropped off) and a medication group (34 cases, 4 cases dropped off). The patients in the medication group were treated with oral administration of metformin hydrochloride, 500 mg each time, twice a day. The patients in the EA group were treated with EA (continuous wave, 2 Hz of frequency) at Zusanli (ST 36), Zhongwan (CV 12), Qihai (CV 6), Yishu (EX-B 3), Shenshu (BL 23), Pishu (BL 20), Ciliao (BL 32) for 30 min, three times a week. One menstrual cycle or 4 weeks were taken as a course of treatment, and 3 continuous courses were given. The follow-up was 3 months. The lipid metabolism indexes of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), homeostasis model assessment-insulin resistance index (HOMA-IR) and testosterone (T) in serum were compared before and after treatment, and the clinical effects of the two groups were evaluated during the follow-up. RESULTS: The total effective rate was 67.7% (21/31) in the EA group and 60.0% (18/30) in the medication group, with no significant difference between the two groups (P>0.05). After treatment, the levels of serum T, HOMA-IR, LDL, TG and TC were decreased significantly in the two groups (P<0.01, P<0.05), and HDL was increased significantly (P<0.01); the levels of TC in the EA group after treatment was lower than that in the medication group (P<0.05). CONCLUSION: EA may adjust some dyslipidemia in patients to correct IR and improve endocrine disorder of PCOS, which had superior/similar effects to metformin.

Potential of Zymomonas mobilis as an electricity producer in ethanol production.

BACKGROUND: Microbial fuel cell (MFC) convokes microorganism to convert biomass into electricity. However, most well-known electrogenic strains cannot directly use glucose to produce valuable products. Zymomonas mobilis, a promising bacterium for ethanol production, owns special Entner-Doudoroff pathway with less ATP and biomass produced and the low-energy coupling respiration, making Z. mobilis a potential exoelectrogen. RESULTS: A glucose-consuming MFC is constructed by inoculating Z. mobilis. The electricity with power density 2.0 mW/m2 is derived from the difference of oxidation-reduction potential (ORP) between anode and cathode chambers. Besides, two-type electricity generation is observed as glucose-independent process and glucose-dependent process. For the sake of enhancing MFC efficiency, extracellular and intracellular strategies are implemented. Biofilm removal and addition of c-type cytochrome benefit electricity performance and Tween 80 accelerates the electricity generation. Perturbation of cellular redox balance compromises the electricity output, indicating that redox homeostasis is the principal requirement to reach ideal voltage. CONCLUSION: This study identifies potential feature of electricity activity for Z. mobilis and provides multiple strategies to enhance the electricity output. Therefore, additional electricity generation will benefit the techno-economic viability of the commercial bulk production for biochemicals or biofuels in an efficient and environmentally sustainable manner.

Computer vision technology-based face mirroring system providing mirror therapy for Bell's palsy patients.

Purpose: Mirror therapy (MT) is an effective adjunct treatment for Bell's palsy (BP); however, a bifold mirror-based apparatus hindered the effectiveness. Besides, few studies have reported the related factors of facial embodiment. The aim of this study was to evaluate the feasibility of a novel face mirroring System (FMS) and the effects on facial embodiment in BP patients, comparing with conventional mirror book (MB) therapy.Method: This was a within-subject design trial. Thirty-six BP patients were recruited and received investigations on user experience and perception of facial embodiment after each facial task (reset, facial expression, and enunciation) when using both FMS and MB separately and randomly.Results: Data of questionnaires showed FMS had a better user experience and perception of facial embodiment comparing with MB. Patients agreed more strongly on the statements of facial embodiment for facial expression and enunciation tasks when using both apparatuses, comparing with rest.Conclusions: The FMS is a feasible and optimal setup to provide MT for BP patients. Moreover, speech paired motor training is a superior strategy for facilitating facial embodiment.Implications for RehabilitationThe Face Mirroring System is a feasible and optimal apparatus for mirror therapy in Bell's palsy patients.Perception of facial embodiment can be increased via combining multiple sensory feedbacks.Speech paired motor tasks have considerable potential to facilitate facial embodiment.

[Therapeutic effects on ovulation and reproduction promotion with acupuncture and clomiphene in polycystic ovary syndrome].

OBJECTIVE: To compare the difference in the therapeutic effects on ovulation disorder in polycystic ovary syndrome (PCOS) between the combined therapy of electroacupuncture and clomiphene and the single medication of clomiphene and to explore the effect mechanism. METHODS: A total of 80 patients of PCOS were randomized into an acupuncture plus medication group (40 cases) and a medication group (40 cases). In the medication group, since the 5th day of menstruation or medicine-withdrawal bleeding, clomiphene was prescribed for oral administration, continuously for 5 days. In the acupuncture plus medication group, the medication was the same as the medication group. Additionally, 30 min electroacupuncture (continuous wave, 2 Hz) was applied to Qihai (CV 6), Guanyuan (CV 4), Zigong (EX-CA 1), Dahe (KI 12), Sanyinjiao (SP 6), Zhongji (CV 3), Diji (SP 8), Shenshu (BL 23), Sanjiaoshu (BL 22) and Ciliao (BL 32), etc. The treatment started on the 5th day of menstruation or medicine-withdrawal bleeding, once every two days, 3 times a week. One cycle of menstruation or 1 month was taken as one course. The treatment cycles were 3 months in the two groups. The level of estradiol (E2) and progesterone (P) in the serum, the endometrial thickness and morphology, ovulation rate and clinical pregnancy rate, as well as the clinical therapeutic effects were compared after treatment in the two groups. RESULTS: Two cases were dropped out because the herbal medicine was taken simultaneously in the acupuncture plus medication group. In the medication group, the medication was discontinued in 3 cases due to gastrointestinal adverse reactions. The total effective rate was 86.8% (33/38) in the acupuncture plus medication group, better than 64.9% (24/37) in the medication group (P<0.05). The ovulation rate in the acupuncture plus medication group was higher than that in the medication group [(86.8%, 33/38) vs (64.9% 24/37), P<0.05]. The pregnancy rate in the acupuncture plus medication group was higher than the medication group in tendency, without significant difference [21.1% (8/38) vs 16.2% (6/37), P>0.05]. After treatment, the results of endometrial thickness and morphology (A-type rate) in the acupuncture plus medication group were better than those in the medication group (P<0.01, P<0.05). After treatment, regarding the levels of E2 and P in the serum in the window period of implantation, the results in the acupuncture plus medication group were higher remarkably than those in the medication group (both P<0.01). CONCLUSION: The combined intervention of electroacupuncture and clomiphene achieves the definite effects of ovulation and pregnancy promotion in PCOS. It remarkably increases the levels of E2 and P in the serum, the endometrial thickness and A-type rate. The therapeutic effects of the combined intervention are remarkably better than those of the simple application of clomiphene. This combined intervention is safe and tolerable for the adverse reactions. The effect mechanisms may be related to the improvements of estrogen, progestin and endometrial receptivity.

[Professor DONG Gui-rong's experience for the treatment of peripheral facial paralysis].

Professor DONG Gui-rong's theoretical principle and manipulation points for peripheral facial paralysis were introduced in details from the angels of syndrome differentiation, timing, acupoint prescription and needling methods. For the syndrome differentiation and timing, the professor emphasized to check the treatment timing and follow the symptoms, which should be treated by stages, besides, it was necessary to find and distinguish the reason and nature of diseases to have a combined treatment of tendons and muscles. For the acupoint prescription and needling methods, he has proposed that the acupoints selection should be compatible of distal and lacal, and made a best of Baihui (GV 20) to regulate the whole yang qi, also he has paid much attention to the needling methods and staging treatment. Under the consideration of late stage of peripheral facial paralysis, based on syndrome differentiation Back-shu points have been selected to regulate zang-fu function, should achieve much better therapeutic effect.

[Clinical study on acupuncture intervention time for treatment of peripheral facial paralysis].

OBJECTIVE: To observe effects of intervention time of local acupuncture at the affected side on the facial nerve injury and the therapeutic effect at acute stage of peripheral facial paralysis. METHODS: Two hundred and seventy-nine cases within 3 days of attack were randomly divided into 4 groups, group A (n=74), group B (n=70), group C (n=74) and control group (n=61). The 4 groups were treated with Prednisone on the third day after attack, and acupuncture was added in the group A, B and C, with Fengchi (GB 20), Yangbai (GB 14), Taiyang (EX-HN 5), Sibai (ST 2), Yingxiang (LI 20), etc. on the affected side and bilateral Hegu (LI 4) selected, and with superficial insertion method used for acupoints on the ear-face parts without manipulating the needles, and electroacupuncture was added from the fifth session of the treatment, and uniform reinforcing-reducing method was used for the distal acupoints selected. The needles were retained for 20 min and the treatment was given for 25 sessions, once other day. The therapeutic effects, the mean therapeutic courses for the cured patients and changes of electroneurography (ENoG) were compared among the groups. RESULTS: The clinical total effective rate was 98.6%, 95.7%, 94.6% and 72.1% in the group A, B, C and the control group, respectively, with a significant difference (P < 0.05), and the therapeutic course for the cured patients increased in the order of the group A, B, C and the control group; and there was no significant difference among the 4 groups in changes of ENoG at the third day and the fourteenth day (both P > 0.05). CONCLUSION: Acute stage is the best opportunity for acupuncture treatment of peripheral facial paralysis, and the earlier the intervention time, the better the therapeutic effect and the shorter the therapeutic course.