Streptomyces are major sources of bioactive natural products. Genome sequencing reveals that Streptomyces have great biosynthetic potential, with an average of 20-40 biosynthetic gene clusters each strain. However, most natural products from Streptomyces are produced in low yields under regular laboratory cultivation conditions, which hamper their further study and drug development. The production of natural products in Streptomyces is controlled by the intricate regulation mechanisms. Manipulation of the regulatory systems that govern secondary metabolite production will strongly facilitate the discovery and development of natural products of Streptomyces origin. In this review, we summarize progresses in pathway-specific regulators from Streptomyces in the last five years and highlight their role in improving the yields of corresponding natural products.
Biological Products ; Multigene Family ; Secondary Metabolism ; Streptomyces/genetics*

Angucyclines/angucyclinones are a large group of polycyclic aromatic polyketides and their producers are widely distributed in nature. This family of natural products attracts great attention because of their diverse biological activities and unique chemical structures. With the development of synthetic biology and the exploitation of the actinomycetes from previously unexplored environments, angucyclines/angucyclinones-like natural products with new skeletons were continuously discovered, thus enriching the structural diversity of this family. In this review we summarize the new angucyclines/angucyclinones analogues discovered in the last decade (2010-2020) by using different strategies, such as changing cultivation conditions, genetic modification, genome mining, bioactivity-guided compound isolation, and fermentation of actinomycetes from underexplored environments. We also discuss the role of synthetic biology in the discovery and development of new compounds of the angucycline/angucyclinone family.
Anthraquinones ; Biological Products ; Polyketides ; Streptomyces

Objective:To investigate the removal of ALTPF pedicled with the lateral branch of the descending branch of the lateral femoral circumflex artery and its application in wound repair.Methods:From January, 2019 to March, 2021, 32 cases of limb wounds were repaired with ALTPF pedicled with the lateral branch of the descending branch of the lateral femoral circumflex artery, including 25 males and 7 females. The age ranged from 21 to 63 years, with an average of 34 years. Injury mechanism: there were 12 cases of traffic accident injury, 8 cases of machine injury, 6 cases of heavy object crushing injury and 6 cases of chronic infectious wound. The area of soft tissue defect was 8.2 cm × 6.3 cm-18.6 cm × 11.2 cm. There were 25 cases of direct suture and 7 cases of free skin grafting. All patients who needed flap repair underwent CTA and high-frequency CDU before operation to judge the approximate direction of the lateral branch of the descending branch of the lateral femoral circumflex artery and the position of the perforating branch. All patients were followed-up regularly for 3 - 13 months, with an average of 11 months.Results:All patients who underwent free flap surgery had no vascular crisis and the flap survived smoothly. At the last follow-up, the appearance of the flap was beautiful without bloating and there were no complications in the donor area.Conclusion:Compared with the traditional ALTPF, the perforator flap of the lateral branch of the descending branch of the anterolateral femoral artery is relatively simple, which can replace the traditional ALTPF to a certain extent, and is worthy of popularization and application in clinic.

Objective:To explore the application of the superficial iliac perforator flap (SCIP) based on the concept of "Donor site under swimming wear" in the repair of wounds of extremities.Methods:From June, 2018 to March, 2019, a total of 20 patients with traumatic soft tissue defects of the extremities were treated. All defects were repaired with free SCIP, including 16 males and 4 females. Location of defects: 10 in the hand, 4 in the forearm, 4 in the shank, and 2 in the foot. Wound areas were 7.3 cm×5.6 cm-16.3 cm×7.7 cm. Patients received routine CTA and high-frequency CDU examinations before surgery to assist in identifying the location of the perforating vessels and the running of the superficial and deep branches of the superficial iliac circumflex artery (SCIA). Combined intraoperative light transmission experiments were used to determine the dominant branch. The superficial branch of SCIA was used as the dominant branch in 18 cases, and the flap was cut in the superficial layer of Scarpa's fascia. The deep branch of SCIA was used as the dominant branch in 2 cases and the flap was cut in the superficial layer of the deep fascia. The donor site was directly sutured. Regular postoperative follow-ups were conducted without lost.Results:All flaps had no vascular crisis after surgery and survived successfully. All patients were followed-up regularly for 8 to 16 months, with an average of 12 months. At the last followed-up, the appearance and texture of the flaps in the recipient area were good, and roughly similar to the healthy tissues around the affected limb. The function of the affected limb recovered well. There was only a linear scar in the donor area.Conclusion:The SCIP based on the concept of "Donor site under swimming wear" is soft in texture, moderate in thickness, and concealed in the supply area. The patient can directly hide the scars of the donor areas after wearing the swimming trunks, which meets the concept of minimizing the damage to the donor area. It deserves to be promoted.

Objective To explore the clinical diagnostic value of bedside lung ultrasound in emergency (BLUE) for patients with postoperative hypoxemia in intensive care unit (ICU). Methods Fifty patients with hypoxemia after ICU surgery postoperation were enrolled in Beijing China-Japan Friendship Hospital from April 2017 to October 2018, the chest X-ray, BLUE and chest CT examinations were performed at the same time, and the diagnostic result of chest CT was the gold standard. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of the 3 methods in the diagnosis of hypoxemia were statistically analyzed, and the results of diagnostic consistency of 3 methods were compared. Results The chest CT findings showed there were 40 cases with different degrees of pneumothorax, pleural effusion, pulmonary consolidation and atelectasis in 50 patients. When the chest X ray was used to diagnose hypoxemia as the pathogenesis, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy rate were 32.5%, 60.0%, 76.47%, 18.18% and 38.0% respectively; the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy rate of BLUE were 80.0%, 70.0%, 91.43%, 46.67% and 78.0% respectively. The consistency test showed that the chest X-ray diagnosis rate of postoperation hypoxemia as the cause was significantly lower than that of chest CT (Kappa = 0.091, P = 0.047) and BLUE (Kappa =0.107, P = 0.031). The consistancy was relatively good when the diagnosis rate of postoperation hypoxemia obtained from BLUE regimen was compared with that obtained from chest CT (Kappa = 0.634, P = 0.000). Conclusion The use of BLUE for diagnosis of hypoxemia being the pathogenesis of the postoperative patients in ICU is superior to the use of routine chest X ray, and compared with applying chest CT, BLUE is faster, more convenient and worthy to be clinically applied widely.

BACKGROUND:Cortical electrical stimulation has achieved good effects in treatment of stroke through animal and clinical experiments.
OBJECTIVE:To observe the effects of a ful y implanted cortical electrical stimulation device with long time, low intensity and various frequencies stimulation protocols on the neurological function recovery in a rat model of local cerebral infarction.
METHODS:The cerebral infarction model was established through middle cerebral artery occlusion in 60 Sprague-Dawley adult male rats. Forty rats with 1-3 points by Bederson scale were detected with magnetic resonance imaging, which was used to confirm cortex infarction and to identify a location for implantation of stimulating electrode over the peri-infarct cortex. Twenty-three rats with cortex infarction were randomly divided into cortical electrical stimulation group (CES group, n=13) and no stimulation group (NS group;n=10). The device was implanted on 6 days after middle cerebral artery occlusion, and the stimulation was given for 16 days. The stimulation program consists of two sessions lasting half an hour each in the morning and in the afternoon respectively. Stimulator delivered biphasic charge balanced pulses (pulse width=200μs) with various frequencies of 50 Hz, 20 Hz and 5 Hz within 10 second blocks and then repeated. The rats of NS group were implanted with the device, but received no electrical stimulation. The behavioral tests, includingforelimb use asymmetry test and foot fault test were performed at 2 and 16 days after implantation. Final y, al of the devices were taken out to test if they were normal y working and al of the rats were sacrificed for hematoxylin-eosin staining, which can reflect the structure of peri-infarct cortex and cellmorphology.
RESULTS AND CONCLUSION:There was only one stimulator in CES group cannot normal y work, and the remaining 22 ones worked wel . The skin covered the implanted stimulator was slightly ulcerated in one rat, and the incisions of the other rats were healed wel . Hematoxylin-eosin staining showed clear and intact structure in peri-infarction cortex (i.e., electrodes were implanted at the cortex), neurons arranged in neat rows, with abundant neuronal cytoplasm and clear nucleolus. The glial cells have complete structures, and there was no edema in the intercellular spaces. Foot-fault and forelimb use asymmetry tests showed the improved neurological function in rats of CES group than that of NS group. We designed a ful-implanted cortical electrical stimulator used in cerebral ischemic rats, and established an implanted method with long time, low intensity and various frequencies pulsed electrical stimulation. The results indicated the stimulation pattern in our study is safe and effective, and it can significantly promote functional recovery in local cerebral infarction rats.

Objective To investigate the effect of implanted cortical electrical stimulation (CES) on the expression of Nissl bodies and growth-associated protein 43 (GAP-43) in the brain after ischemic injury,and its mechanism.Methods Models of middle cerebral artery occlusion (MCAO) were established in 23 male Sprague-Dawley rats.They were randomly divided into a CES group (CES,n=13) and a no stimulation group (NS,n=10) and electrical stimulators were implanted in both groups.CES was applied for 14 d in the CES group but not in the NS group.The expression of Nissl bodies and GAP-43 around the infarct were quantified using version 6.0 of the ImagePro Plus system.Results In the CES group the Nissl bodies had a deep color,and their percentage of area was higher than that in the NS group.The GAP-43 positive expression area also had a relatively deep color,and the average percentage of positive expression area was also higher than that in the NS group.Conclusions CES can enhance the expression of Nissl bodies and GAP-43 after cerebral infarction.This suggests that CES can promote axon growth and the formation of new neural circuits.

OBJECTIVETo investigate antitumor constituents from n-butyl alcohol extract of Alternanthera philoxeroides.

METHODThe constituents were isolated with silica gel, gel permeation chromatography, and purified by HPLC. Their structures were elucidated by spectroscopy and acid hydrolysis. The antitumor effects of extracts and isolated compounds were tested by MTH method in vitro.

RESULTSeven compounds were isolated and elucidated as followings: oleanolic acid 3-O-beta-D-glucuronopyranoside (1), oleanolic acid 28-O-beta-D-glucopyranoside (2), oleanolic acid 3-O-beta-D-glucuronopyranoside-6'-O-methyl ester (3), chikusetsusaponin IV a methyl ester (4), hederagenin 3-O-beta-D-glucuronopyranoside-6'-O-methyl ester (5), 4,5-dihydroblumenol (6), 6S,7E,9R-6,9-di-hydroxymegastigma-4,7-dien-3-one-9-O-beta-D-glucopyranoside (7). Compound 1 showed significant inhibitory effect against Hela and L929 with inhibitive ratios 91.3% and 92.9% at 30 mg x L(-1), respectively.

CONCLUSIONCompounds 4, 5 and 7 were isolated from this genus for the first time. Compound 1 showed significant inhibitory effect against Hela and L929 at 30 mg x L(-1).

Amaranthaceae ; chemistry ; Antineoplastic Agents ; chemistry ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Humans ; Hydrolysis

Objective To develop an HPLC method for determination of triptoquinone H in Tripterygium wilfordii and its Tablet preparations. Methods An external method with Agilent Zorbax SC-C_(8)(250 mm?4.6 mm, 5 ?m) column as fixed phase and methanol-water (75∶25) as mobile phase was adopted. The detective wavelength was 258 nm and the flow rate was 1.0 mL/min. Results The linearity range of triptoquinone was 6.28 — 100.5 ?g/mL (r=0.999 7). The average recovery of T. wilfordii was 96.94%, RSD was 1.57% (n=9) and the average recovery of T. hypoglaucum Tablet was 100.02%, RSD was 1.74% (n=9). Conclusion The method is accurate and sensitive. It is adoptable for quantity analysis of triptoquinone H in T. wilfordii and its Tablet.