[Application of process analysis technology in traditional Chinese medicine manufacturing industry].

In the traditional Chinese medicine(TCM) manufacturing industry, quality control determines the safety, effectiveness, and quality stability of the final product. The traditional quality control method generally carries out sampling off-line testing of drugs after the end of the batch production, which is incomprehensive, and it fails to find the problems in the production process in time. Process analysis technology(PAT) uses process testing, mathematical modeling, data analysis, and other technologies to collect, analyze, feedback, control, and continuously improve the critical quality attributes(CQA) in all aspects of the production of TCM preparations in real time. The application of PAT in the TCM manufacturing industry is one of the research hotspots in recent years, which has the advantages of real-time, systematic, non-destructive, green, and rapid detection for the production quality control of TCM preparations. It can effectively ensure the stability of the quality of TCM preparations, improve production efficiency, and play a key role in the study of the quantity and quality transfer law of TCM. Commonly used PAT includes near-infrared spectroscopy, Raman spectroscopy, online microwave, etc. In addition, the establishment of an online detection model by PAT is the key basic work to realize intelligent manufacturing in TCM production. Obtaining real-time online detection data through PAT and establishing a closed-loop control model on this basis are a key common technical difficulty in the industry. This paper adopted systematic literature analysis to summarize the relevant Chinese and foreign literature, policies and regulations, and production applications, and it introduced the development trend and practical application of PAT, so as to provide references for accelerating the application of PAT in the TCM manufacturing industry, the intelligent transformation and upgrading, and high-quality development of the TCM industry.

[Current status, trends, and challenges of continuous manufacturing technology for oral traditional Chinese medicine solid preparations].

In recent years, continuous manufacturing technology has attracted considerable attention in the pharmaceutical industry. This technology is highly sought after for its significant advantages in cost reduction, increased efficiency, and improved productivity, making it a growing trend in the future of the pharmaceutical industry. Compared to traditional batch production methods, continuous manufacturing technology features real-time control and environmentally friendly intelligence, enabling pharmaceutical companies to produce drugs more efficiently. However, the adoption of continuous manufacturing technology has been slow in the field of traditional Chinese medicine(TCM) pharmaceuticals. On the one hand, there is insufficient research on continuous manufacturing equipment and technology that align with the characteristics of TCM preparations. On the other hand, the scarcity of talent with diverse expertise hampers its development. Therefore, in order to promote the modernization and upgrading of the TCM pharmaceutical industry, this article combined the current development status of the TCM industry to outline the development status and regulatory requirements of continuous manufacturing technology. At the same time, it analyzed the problems with existing TCM manufacturing models and explored the prospects and challenges of applying continuous manufacturing technology in the field of TCM pharmaceuticals. The analysis focused on continuous manufacturing control strategies, technical tools, and pharmaceutical equipment, aiming to provide targeted recommendations to drive the development of the TCM pharmaceutical industry.

CD69 serves as a potential diagnostic and prognostic biomarker for hepatocellular carcinoma.

The prevalence and mortality of hepatocellular carcinoma (HCC) are still increasing. This study aimed to identify potential therapeutic targets related to patient prognosis. Data were downloaded from TCGA, GSE25097, GSE36376, and GSE76427 datasets. Differential analysis and enrichment analysis were performed in HCC. Cell deaths were evaluated, and least absolute shrinkage and selection operator regression (LASSO) regression was analyzed to screen candidate genes. Additionally, immune cell infiltration in HCC was assessed. We identified 4088 common DEGs with the same direction of differential expression in all four datasets, they were mainly enriched in immunoinflammation and cell cycle pathways. Apoptosis was significantly suppressed in HCC in GSEA and GSVA. After LASSO regression analysis, we screened CD69, CDC25B, MGMT, TOP2A, and TXNIP as candidate genes. Among them, CD69 significantly influenced the overall survival of HCC patients in both TCGA and GSE76427. CD69 may be a protective factor for outcome of HCC patients. In addition, CD69 was positive correlation with T cells and CD3E. CD69, CDC25B, MGMT, TOP2A, and TXNIP were potential diagnostic and prognostic target for HCC, especially CD69.

Evaluation of coating uniformity for the digestion-aid tablets by portable near-infrared spectroscopy.

Process analysis can effectively stabilize pharmaceutical quality and optimize the control of production process. For the sustained-release digestion-aid tablets, the coating film thickness is an important indicator to measure the quality of products. Traditional method mainly spot-checks tablets and measures with visual microscopy, which is time-consuming and laborious. This study attempted to use a portable near-infrared spectroscopy for rapid detection of a Chinese medicine tablets from production line. First, PLS regression models were established for coating film at twelve different locations of the tablet section, and the results showed that the correlation coefficients of training and validation sets were all over 0.80. Subsequently, the twelve locations were divided into six groups to further establish regressions. After chemometrics optimization, the optimal of six group models were generally better than single location models, with Rc2 and Rv2 all above 0.85, and RMSEV values all below 2.0. The mean relative error of prediction of the optimal model was 9.49%. The pharmaceutical process detection based on the portable NIR spectroscopy met the demand of managing digestion-aid tablet coating data conveniently. The proposed approach can successfully realize on-site and online pharmaceutical monitoring and has a promising practical value.

'Stateful' threshold switching for neuromorphic learning.

Memristors have promising prospects in developing neuromorphic chips that parallel the brain-level power efficiency and brain-like computational functions. However, the limited available ON/OFF states and high switching voltage in conventional resistive switching (RS) constrain its practical and flexible implementations to emulate biological synaptic functions with low power consumption. We present 'stateful' threshold switching (TS) within the millivoltage range depending on the resistive states of RS, which originates from the charging/discharging parasitic elements of a memristive circuit. Fundamental neuromorphic learning can be facilely implemented based on a single memristor by utilizing four resistive states in 'stateful' TS. Besides the metaplasticity of synaptic learning-forgetting behaviors, multifunctional associative learning, involving acquisition, extinction, recovery, generalization and protective inhibition, was realized with nonpolar operation and power consumption of 5.71 pW. The featured 'stateful' TS with flexible tunability, enriched states, and ultralow operating voltage will provide new directions toward a massive storage unit and bio-inspired neuromorphic system.

Correction: 'Stateful' threshold switching for neuromorphic learning.

Correction for ''Stateful' threshold switching for neuromorphic learning' by Zhijian Zhong et al., Nanoscale, 2022, DOI: 10.1039/d1nr05502j.

Evaluation of Early Retinal Nerve Injury in Type 2 Diabetes Patients Without Diabetic Retinopathy.

Objectives: To investigate the damage to the retinal nerve fiber layer (RNFL) and ganglion cell complex layer (GCL+) in diabetic patients without retinal microangioma and to determine the kind of nerve damage more likely to indicate early injury. Subjects and Methods: We included 360 patients (360 eyes) with type 2 diabetes mellitus and 168 healthy volunteers (168 eyes). Patients with retinal microangioma were excluded by fundus fluorescein angiography (FFA). The parameters around the optic disc and macular area were measured by optical coherence tomography (OCT). Results: The peripapillary RNFL thickness was thinner in the temporal (72.98 ± 13.76 µm, P < 0.0001) and inferior (120.71 ± 21.43 µm, P = 0.0103) sectors in patients with no diabetic retinopathy (NDR) compared to healthy controls. The reduction of retinal thickness in the macular region was prominent in the inferior sector in patients (34.74 ± 4.92 µm, P < 0.0001) compared to normal controls. Thinning of GCL+ in the second region of the macular area was significant in patients with NDR compared to normal controls (P < 0.05). However, no difference in the GCL+ and retinal thicknesses of the central macular region was observed between the patients with NDR and healthy controls. Using the 5th percentile (P5) of normal controls as the reference value, we found that the parameters with the highest indices in patients with NDR were the inferior and temporal peripapillary RNFL thickness (13.0%), the inferior RNFL thickness in the macular area (20%), the inferior retinal thickness in the outer ring of the macular area (10.8%), and the inferior GCL+ thickness in the macular area (10.6%). The GCL+ and RNFL thicknesses in the central macular area accounted for the smallest proportion in P5 of normal controls (3%). Conclusions: Retinal nerve injury can occur in patients without retinal microangioma. The inferior RNFL in the macular area and the inferior and temporal peripapillary RNFL were most sensitive to glucose damage. These areas might be associated with early detection of diabetic retinopathy (DR) as they are more likely to indicate early damage.

Diagnostic Value of Systematic Imaging Examination in Embedded Optic Disc Drusen in Adolescents with Mild Visual Impairment.

AIM: To evaluate the diagnostic value of systematic ophthalmologic imaging examination in the diagnosis of embedded optic disc drusen (ODD) in adolescents with mild visual impairment. METHODS: Eleven patients were evaluated through optometric examination, fundus photography, visual field inspection, optical coherence tomography (OCT), ultrasonography (US), and fundus fluorescein angiography (FFA). Of the 11 patients, three also underwent cranial and orbital magnetic resonance imaging (MRI). RESULTS: All 11 patients had either no apparent abnormality or only mild refractive abnormalities. In all patients, fundus inspection revealed flushing the optic disc with varying degrees of limited boundary ambiguity and optic disc congestion with disappearance of the fovea. One patient had a visual field defect during the period of edema of ODD, but the visual field returned to normal after the optic disc edema subsided. US revealed discoid acousto-optic masses in front of the optic disc in six patients. OCT showed a slight elevation and thinning of the retinal nerve fiber layer (RNFL) of the optic disc in all patients. Quasicircular, hyperreflex signals of different sizes could be observed below the RNFL. Late-stage FFA revealed focal staining at the edge of the optic disc without fluorescence leakage in all patients. Orbital and cranial MRI findings were normal in the three patients. CONCLUSION: A systematic ophthalmologic imaging examination can not only improve the detection rate of embedded ODD but also avoid excessive examinations and treatments.

Dihydromyricetin induces apoptosis and cytoprotective autophagy through ROS-NF-κB signalling in human melanoma cells.

Dihydromyricetin (DHM), a Rattan tea extract, has recently been shown to have anti-cancer activity in mammalian cells. In this study, we investigated the effect of DHM on human melanoma cells. Apart from induction of apoptosis, we demonstrated that DHM induced an autophagic response. Moreover, pharmacological inhibition or genetic blockade of autophagy enhanced DHM-induced cell death and apoptosis, indicating the cytoprotective role of autophagy in DHM-treated human melanoma cells. Further study suggested that the nuclear factor kappa B (NF-κB) signalling pathway was involved in DHM-induced autophagy. Moreover, N-acetyl-cysteine (NAC), an ROS scavenger, abrogated the effects of DHM on NF-κB-dependent autophagy. Taken together, this evidence demonstrates that a strategy of blocking ROS-NF-κB-dependent autophagy to enhance the activity of DHM warrants further attention for the treatment of human melanoma.

Antihyperglycemic effect of ganoderma lucidum polysaccharides on streptozotocin-induced diabetic mice.

The current study evaluated the glucose-lowering effect of ganoderma lucidum polysaccharides (Gl-PS) in streptozotocin (STZ)-induced diabetic mice. The diabetic mice were randomly divided into four groups (8 mice per group): diabetic control group, low-dose Gl-PS treated group (50 mg/kg, Gl-PS), high-dose Gl-PS treated group (150 mg/kg, Gl-PS) and positive drug control treated group (glibenclamide, 4 mg/kg), with normal mice used as the control group. Body weights, fasting blood glucose (FBG), serum insulin and blood lipid levels of mice were measured. After 28 days of treatment with Gl-PS, body weights and serum insulin levels of the Gl-PS treated groups was significantly higher than that of the diabetic control group, whereas FBG levels was significantly lower. Moreover, total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) levels of the Gl-PS treated groups had dropped, whereas the high density lipoprotein cholesterol (HDL-C) levels had increased. In addition, according to acute toxicity studies, Gl-PS did not cause behavioral changes and any death of mice. These data suggest that Gl-PS has an antihyperglycemic effect. Furthermore, considering the Gl-PS effects on lipid profile, it may be a potential hypolipidaemic agent, which will be a great advantage in treating diabetic conditions associated with atherosclerosis or hyperlipidemia.

DFT and MP2 investigations of L-proline and its hydrated complexes.

A theoretical study of L-proline-nH(2)O (n = 1-3) has been performed using the hybrid DFT-B3LYP and MP2 methods together with the 6-311++G(d,p) basis set. The results show that the P2 conformer is energetically favorable when forming a hydrated structure, and the hydration of the carboxyl group leads to the greatest stability. For hydrated complexes, the adiabatic and vertical singlet-triplet excitation energies tend to decrease with the addition of water molecules. The hydration energy indicates that in the hydrated complexes the order of stability is: binding site 2 > binding site 1 > binding site 3, and binding site 12 > binding site 23 > binding site 13. As water molecules are added, the stabilities of these hydrated structures gradually increase. In addition, an infrared frequency analysis indicated that there are some differences in the low-frequency range, which are mainly dominated by the O-H stretching or bending vibrations of different water molecules. All of these results should aid our understanding of molecular behavior and provide reference data for further studies of biological systems.

Sharp and asymmetric transmission response in metal-dielectric-metal plasmonic waveguides containing Kerr nonlinear media.

Based on the excitation of surface plasmon polaritons (SPPs), we analytically and numerically investigate the transmission response in metal-dielectric-metal (MDM) plasmonic waveguides with a side coupled nanocavity (SCNC). By filling the nanocavity with a Kerr nonlinear medium, the position of the resonant dip in the transmission spectrum can be tuned by the incident light intensity. The oscillation of a Fabry-Perot nanocavity formed by incorporating a finite length of the same Kerr nonlinear media into the MDM waveguide acts as a background for the transmission response of the system and induces a sharp and asymmetric response line shape. As a result, the wavelength shift required for the plasmonic device to be switched from the maximum to the minimum transmission can be reduced by half in a structure less than 400 nm long. Such an effect may be potentially applied to constructing SPP-based all-optical switching with low power threshold at nanoscale.