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In China, the exploitation of most unconventional oil and gas reservoirs is dependent on hydraulic fracturing, which is a key method employed when developing tight gas formations. Numerous scholars and field engineers, both domestically and internationally, have conducted extensive numerical simulations and physical experiments to study crack propagation and predict post-fracturing productivity in hydraulic fracturing. Although some progress has been reported in this regard, it is difficult to accurately predict the well productivity using mechanistic models owing to the vertical multilayered development of tight gas reservoirs. In this study, vertical fractured wells in a block of Sulige gas field were examined. The block relied on hydraulic fracturing to produce tight gases. However, as development progressed, the available reservoir environment deteriorated, large differences emerged between wells after fracturing, and the fracturing results did not meet the expectations. In this study, geological, construction, and generation data for this block that had been collected since 2007 were analyzed. After applying multiple machine-learning methods to filter outliers and fill in missing values, k-means clustering, classification enhancement, extreme gradient enhancement, and LightGBM algorithms were used to establish a regression model. The analysis results revealed that the regression accuracy of the cluster test set was as high as 70% and that the LightGBM model had the best regression effect among the 227 stripper wells in the block. After optimizing the fracturing construction parameters (fracturing fluid volume, proppant volume, liquid-nitrogen volume, and pumping rate), the average fracturing fluid and liquid-nitrogen volumes per well decreased, whereas the unit reservoir proppant and liquid-nitrogen volumes increased. The results also revealed that 182 wells showed an improved initial production capacity during fracturing. The average gas production index per meter increased by 22.04%. This approach enabled rapid and efficient production forecasting and construction optimization. Moreover, this represents a novel fracture design method that is applicable to onsite engineers in tight gas production fields in the Ordos region.

Background: With the increasing prevalence of obesity and metabolic syndrome, the incidence of non-alcoholic fatty liver disease (NAFLD) is also increasing. In the next decade, NAFLD may become the main cause of liver transplantation. Therefore, the choice of treatment plan is particularly important. The purpose of this study was to compare several interventions in the treatment of NAFLD to provide some reference for clinicians in selecting treatment methods.Methods: We searched Public Medicine (PubMed), Medline, Excerpta Medica Database (Embase), and Cochrane Library from January 2013 to January 2023 to identify randomized controlled trials (RCTs) published in English. The network meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Forty-three studies accounting for a total of 2,969 patients were included, and alanine aminotransferase (ALT), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL) were selected as outcome measures for analysis and comparison.Results: We evaluated the results of drug, diet, and lifestyle interventions between the intervention and control groups. Curcumin (CUN) and probiotics (PTC) were selected for medication, the Mediterranean diet (MDED) was selected for special diet (SPD), and various kinds of exercise and lifestyle advice were selected for lifestyle interventions (LFT). The SUCRA was used to rank interventions according to the effect on ALT indicators (SUCRA: PTC 80.3%, SPD 65.2%, LFT 61.4%, PLB 32.8%, CUN 10.2%), TC indicators (SUCRA: PTC 89.4%, SPD 64%, CUN 34%, LFT 36.6%, PLB 17%), and LDL indicators (SUCRA: PTC 84.2%, CUN 69.5%, LFT 51.7%, PLB 30.1%, SPD 14.5%). The pairwise meta-analysis results showed that MDED was significantly better than NT in improving ALT [SMD 1.99, 95% CI (0.38, 3.60)]. In terms of improving TC and LDL, ATS was significantly better than NT [SMD 0.19, 95% CI (0.03, 0.36)] [SMD 0.18, 95% CI (0.01, 0.35)].Conclusion: Our study showed that PTC is most likely to be the most effective treatment for improving NAFLD indicators. Professional advice on diet or exercise was more effective in treating NAFLD than no intervention.

Hair cells of the auditory and vestibular systems display astonishing sensitivity, frequency selectivity, and temporal resolution to external signals. These specialized cells utilize an internal active amplifier to achieve highly sensitive mechanical detection. One of the manifestations of this active process is the occurrence of spontaneous limit-cycle motion of the hair-cell bundle. As hair bundles under in vivo conditions are typically coupled to each other by overlying structures, we explore the role of this coupling on the dynamics of the system, using a combination of theoretical and experimental approaches. Our numerical model suggests that the presence of chaotic dynamics in the response of individual bundles enhances their ability to synchronize when coupled, resulting in significant improvement in the system's ability to detect weak signals. This synchronization persists even for a large frequency dispersion and when tens of oscillators comprise the system. Further, the amplitude and coherence of the active motion are not reduced upon increasing the number of oscillators. Using artificial membranes, we impose mechanical coupling on groups of live and functional hair bundles, selected from in vitro preparations of the sensory epithelium, allowing us to explore the role of coupling experimentally. Consistent with the numerical simulations of the chaotic system, synchronization occurs even for large frequency dispersion and a large number of hair cells. Further, the amplitude and coherence of the spontaneous oscillations are independent of the number of hair cells in the network. We therefore propose that hair cells utilize their chaotic dynamics to stabilize the synchronized state and avoid the amplitude death regime, resulting in collective coherent motion that could play a role in generating spontaneous otoacoustic emissions and an enhanced ability to detect weak signals.

Sinomenine is a nonaddictive alkaloid used to prevent morphine dependence, even thoughits mechanism isnot fully understood. Astrocytes aggravate the pathological process in their neighboring cellsthrough exosomes in central nervous system diseases. However, the effect of sinomenine on astrocyte-derived exosomes for the amelioration of morphine dependence has not been reported yet. In this study, we found that sinomenine prevented the morphine-induced conditionedplace preference in mice. Sinomenine reduced the levels of cAMP and intracellular Ca2+ in morphine-treated SH-SY5Y cells. Moreover, sinomenine inhibited the expressions of p-NMDAR1/NMDAR1, p-CAMKII/CAMKII, and p-CREB/CREB in the hippocampusof morphine-dependent mice and SH-SY5Y cells. Furthermore, we found that sinomenine inhibitedthe morphine-induced activation of astrocytesin vivo and in vitro. Afterwards, exosomes were isolated from cultured primary astrocytes treated with phosphate buffer saline (PBS, ctl-exo), morphine (mor-exo), or morphine and sinomenine (Sino-exo). Subsequently, morphine-treated SH-SY5Y cells were treated with ctl-exo, mor-exo, and Sino-exo. Results showed that Sino-exo reduced the level of cAMP, intracellular Ca2+, and the expression of p-CAMKII/CAMKII and p-CREB/CREB in morphine-treated SH-SY5Y cells. In conclusion, we demonstrated that sinomenine exhibited protective effects against morphine dependencein vivo and in vitro through theNMDAR1/CAMKII/CREB pathway. Sinomenine-induced alterationof the function of astrocyte-derived exosomes may contribute to the antidependence effects of sinomenine in morphine dependence.

Cinnamomi Cortex is a commonly used herb with a variety of pharmacological effects. We investigated the molecular mechanisms by which Cinnamomi Cortex antagonises morphine addiction (MA) using network pharmacology and molecular docking techniques in a morphine-dependent rat withdrawal model. The antagonistic effect of Cinnamomi Cortex was observed by inducing withdrawal symptoms in morphine-dependent rats through a dose-escalation method. Network pharmacology and molecular docking techniques were further employed to analyze the substance basis and mechanism of Cinnamomi Cortex in antagonizing MA. Cinnamomi Cortex was screened to contain 10 active ingredients, 127 active targets and 1724 MA-related targets. Among them, 52 targets overlapped between Cinnamomi Cortex and MA and 13 core targets were identified by metric analysis. Cinnamomi Cortex had a significant inhibitory effect on withdrawal symptoms in MA rats, with the most pronounced effect at a moderate dose. The active ingredients of Cinnamomi Cortex (including oleic acid) can act on multiple targets related to MA and regulate multiple pathways to treat MA. The present study reveals the material basis and mechanism of cinnamon's action on MA, and provides insights and references for subsequent experiments exploring the potential therapeutic approach of Cinnamomi Cortex on MA. [ABSTRACT FROM AUTHOR]

Objective: Heterotopic ossification (HO) refers to the abnormal development of bone in soft tissue rather than within bone itself. Previous research has shown that sensory nerve prostaglandin E2 receptor 4 (EP4) signaling not only governs pain perception but also influences bone formation. However, the relationship between sensory nerve EP4 and the pathogenesis of HO in the Achilles tendon remains unclear. This study aims to investigate this relationship and the underlying mechanisms. Methods: We generated sensory nerve EP4-specific knockout mice, with the genotype of Avil-CreEP4fl/fl, was propagated. Transcriptome sequencing and bioinformatics analysis techniques were used to identify the potential molecular pathways involving with sensory nerve EP4. Additionally, a neurectomy mouse model was created by transecting the sciatic nerve transection, to examine the effects and mechanisms of peripheral innervation on HO in vivo. Micro-CT, immunofluorescence (IF), Hematoxylin and Eosin (H&E) Staining, Safranin O-Fast Green staining and western blotting were used to analyze changes in cellular and tissue components. Results: We here observed an increase in sensory nerve EP4 and H-type vessels during the pathogenesis of HO in both human subjects and mice. Proximal neurectomy through sciatic nerve transection or the targeted knockout of EP4 in sensory nerves hindered angiogenesis-dependent bone formation and the development of HO at the traumatic site of the Achilles tendon. Furthermore, we identified the Efnb2 (Ephrin-B2)/Dll4 (Delta-like ligand 4) axis as a potential downstream element influenced by sensory nerve EP4 in the regulation of HO. Notably, administration of an EP4 inhibitor demonstrated the ability to alleviate HO. Based on these findings, sensory nerve EP4 emerges as an innovative and promising approach for managing HO. Conclusion: Our findings demonstrate that the sensory nerve EP4 promotes ectopic bone formation by modulating angiogenesis-associated osteogenesis during HO. The translational potential of this article: Our results provide a mechanistic rationale for targeting sensory nerve EP4 as a promising candidate for HO therapy.

Abstract Chondrocyte senescence and reduced lubrication play pivotal roles in the pathogenesis of age‐related osteoarthritis (OA). In the present study, highly lubricated and drug‐loaded hydrogel microspheres are designed and fabricated through the radical polymerization of sulfobetaine (SB)‐modified hyaluronic acid methacrylate using microfluidic technology. The copolymer contains a large number of SB and carboxyl groups that can provide a high degree of lubrication through hydration and form electrostatic loading interactions with metformin (Met@SBHA), producing a high drug load for anti‐chondrocyte senescence. Mechanical, tribological, and drug release analyses demonstrated enhanced lubricative properties and prolonged drug dissemination of the Met@SBHA microspheres. RNA sequencing (RNA‐seq) analysis, network pharmacology, and in vitro assays revealed the extraordinary capacity of Met@SBHA to combat chondrocyte senescence. Additionally, inducible nitric oxide synthase (iNOS) has been identified as a promising protein modulated by Met in senescent chondrocytes, thereby exerting a significant influence on the iNOS/ONOO‐/P53 pathway. Notably, the intra‐articular administration of Met@SBHA in aged mice ameliorated cartilage senescence and OA pathogenesis. Based on the findings of this study, Met@SBHA emerges as an innovative and promising strategy in tackling age‐related OA serving the dual function of enhancing joint lubrication and mitigating cartilage senescence.

Agriculture is a significant source of carbon emissions, which have a substantial environmental impact. The digital economy plays a vital role in mitigating these emissions through innovative digital solutions. As a leading agricultural nation, China faces substantial pressure to reduce its agricultural carbon emissions(ACE). This paper aims to thoroughly examine the relationship between the growth of the rural digital economy and ACE. To achieve this, we utilize an extensive panel dataset covering China's provinces from 2011 to 2020, analyzing the dynamic and spatial effects of digital economy development on ACE. The key findings of this research are as follows: (1) The rapid expansion of the digital economy significantly reduces ACE. (2) The impact of digital economic development on lowering ACE varies spatially, with a clear progression from eastern to western regions. (3) The digital economy helps reduce ACE through three specific channels: fostering technological innovation, enhancing scale efficiency management, and providing agricultural financial incentives. Based on these findings, this study proposes policy recommendations to improve digital infrastructure, promote balanced regional development in the digital economy, and optimize the management of agricultural science and technology. These policy insights aim to transform agriculture and achieve the goal of reducing ACE, thereby contributing to broader environmental sustainability.

Abstract Normal epithelial cells exert their competitive advantage over RasV12-transformed cells and eliminate them into the apical lumen via cell competition. However, the internal or external factors that compromise cell competition and provoke carcinogenesis remain elusive. In this study, we examine the effect of sequential accumulation of gene mutations, mimicking multi-sequential carcinogenesis on RasV12-induced cell competition in intestinal epithelial tissues. Consequently, we find that the directionality of RasV12-cell extrusion in Wnt-activated epithelia is reversed, and transformed cells are delaminated into the basal lamina via non-cell autonomous MMP21 upregulation. Subsequently, diffusively infiltrating, transformed cells develop into highly invasive carcinomas. The elevated production of MMP21 is elicited partly through NF-κB signaling, blockage of which restores apical elimination of RasV12 cells. We further demonstrate that the NF-κB-MMP21 axis is significantly bolstered in early colorectal carcinoma in humans. Collectively, this study shows that cells with high mutational burdens exploit cell competition for their benefit by behaving as unfit cells, endowing them with an invasion advantage.

Objectives: Long, ineffective, and toxic regimens hinder the treatment of patients with multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant tuberculosis (pre-XDR-TB). Methods: We conducted a multicenter cohort study to prospectively evaluate the safety and efficacy of three 9-month, all-oral, 5-drug regimens. Regimen A (bedaquiline [Bdq]+linezolid [Lzd]+moxifloxacin [Mfx]+cycloserine [Cs]+pyrazinamide [Pza]) and Regimen B (Lzd+Mfx+Cs+clofazimine [Cfz]+Pza) were used to treat MDR-TB patients (Groups A and B, respectively, assigned according to the patient's treatment preference), while Regimen C (Bdq+Lzd+Cs+Cfz+Pza) was used to treat pre-XDR-TB patients (Group C). The primary endpoint was the occurrence of an unfavorable outcome within 12 months of treatment completion, regardless of regimen. Results: A total of 104 patients (34 in Group A, 46 in Group B, and 24 in Group C), with a median age of 35.5 (29.0-54.0) years, were included in the analysis population. At 12 months after treatment completion, five patients were deemed non-assessable. Of the remaining 99 participants, seven (7.1%) had an unfavorable outcome (including two deaths from any cause, four with treatment failure, and one loss to follow-up) and 92 (92.9%) had a favorable outcome. Culture conversion was achieved in 82.5% (80/97) of participants at month 2 and in 97.9% (94/97) of participants at month 6. Adverse events (AEs) resulting in drug adjustment occurred in 69.2% (72/104) of participants, mainly due to Lzd and Pza use. A QT interval prolongation of ≥ 500 ms occurred in 5.8% (6/104) of participants. Conclusion: The primary outcome of the three tailored, 9-month, all-oral, 5-drug regimens was satisfactory in the vast majority of MDR-TB and pre-XDR-TB patients, with manageable and reversible AEs.

Background Triticale (×Triticosecale Wittmack L.), rye (Secale cereale L.), and oat (Avena sativa L.) are the main forage crops on the Qinghai–Tibet Plateau, but there has been relatively little research on the silage produced from these three species. Methods Plants were harvested at the heading, flowering, grouting, milky, and dough stages and then used to produce silage with and without additives (Sila-Max and Sila-Mix). The nutritional quality of the resulting silages was analyzed. Results Triticale was revealed to be more suitable than oat or rye for producing silage on the Qinghai–Tibet Plateau. On the basis of the dry matter yield (DMY), triticale and rye should be harvested at the milky stage to optimize silage quality, whereas oat should be harvested at the dough stage. The lactic acid bacteria additives Sila-Max and Sila-Mix had no significant effect on the nutritional quality of the three silages regardless of when the samples were harvested. Overall, triticale produced higher quality silage than oat or rye. More specifically, triticale variety ‘Gannong No.2’ harvested at the milky stage is ideal for silage production.

Abstract The mechanisms that coordinate the shift from joint homeostasis to osteoarthritis (OA) remain unknown. No pharmacological intervention can currently prevent the progression of osteoarthritis. Accumulating evidence has shown that subchondral bone deterioration is a primary trigger for overlying cartilage degeneration. We previously found that H-type vessels modulate aberrant subchondral bone formation during the pathogenesis of OA. However, the mechanism responsible for the elevation of H-type vessels in OA is still unclear. Here, we found that PDGFR-β expression, predominantly in the CD31hiEmcnhi endothelium, was substantially elevated in subchondral bones from OA patients and rodent OA models. A mouse model of OA with deletion of PDGFR-β in endothelial cells (ECs) exhibited fewer H-type vessels, ameliorated subchondral bone deterioration and alleviated overlying cartilage degeneration. Endothelial PDGFR-β promotes angiogenesis through the formation of the PDGFR-β/talin1/FAK complex. Notably, endothelium-specific inhibition of PDGFR-β by local injection of AAV9 in subchondral bone effectively attenuated the pathogenesis of OA compared with that of the vehicle-treated controls. Based on the results from this study, targeting PDGFR-β is a novel and promising approach for the prevention or early treatment of OA.

Background: Multidrug-resistant tuberculosis (MDR-TB) patients have been suffering long, ineffective, and toxic treatment until short-course injectable-free regimens emerged. However, the new WHO-recommended regimens might be less feasible in the real-world setting. Here, we evaluated two optimized all-oral short-course regimens in China. Methods: From April 2019 to August 2020, we conducted a prospective nonrandomized controlled trial and consecutively included 103 MDR-TB patients diagnosed with pulmonary MDR-TB in Shenzhen, China. A 4-5 drug regimen of 9-12 months was tailored to the strain's resistance patterns, patients' affordability, and tolerance to drugs. This was an interim analysis, focusing on the early treatment period. Results: 53.4% (55/103) of patients were prescribed linezolid, fluoroquinolone (FQ), clofazimine, cycloserine, and pyrazinamide, followed by a regimen in which clofazimine was replaced by bedaquiline (35/103, 34.0%). The culture conversion rate was 83.1% and 94.4% at two and four months, respectively, with no significant difference between bedaquiline-free and bedaquiline-containing cases and between FQ-susceptible and FQ-resistant cases. Among 41 patients who completed treatment, 40 (97.6%) patients had a favorable outcome and no relapse was observed. Peripheral neuropathy and arthralgia/myalgia were the most frequent AEs (56.3%, 58/103). 18 AEs caused permanent discontinuation of drugs, mostly due to pyrazinamide and linezolid. Conclusion: Optimized all-oral short-course regimens showed satisfactory efficacy and safety in early treatment stage. Further research is needed to confirm these results.

Informal groundwater markets have spontaneously developed in Pakistan due to the heterogeneity of farmers’ resource endowments, irrigation water shortages, and productivity gains of groundwater. Evidence shows that water allocation through formal or informal water markets can result in significant benefits for buyers and sellers and improve sustainable water use. Existing literature on water markets generally takes only buyers’ perspectives into account when studying the factors influencing the purchase of groundwater for irrigation. In contrast, we look at the perspectives of both buyers and sellers to investigate farmers’ participation in informal water markets. We conducted this study in the three agroecological zones of Punjab. The data was collected from a sample size of 360 farmers, with an equal proportion of water buyers, sellers, and self-users. Cragg’s double hurdle model was used to investigate the factors influencing the extent of water buying or selling. Results of the demand side analysis show that educated has negative correlation with water market participation and level of water purchasing. In addition, large farmers are less likely to buy water, indicating that the majority of farmers in water markets are smallholders. However, the degree of land fragmentation, soil fertility, and adoption of improved seeds each have may increase water market participation. Water cost and farmers’ family size has negative impact on level of water purchasing. The results of supply side analysis show that tubewell capacity, degree of land fragmentation, and the number of operational tubewells at a given farm have a positive relationship with the likelihood of selling water. When it comes to the amount of water sold, two factors that positively influence the extent of water selling are the income from water sales and the degree of land fragmentation. Finally, we discuss the implications of these results for sustainable water extraction in the water markets.

Pakistan is the world’s third-largest user of groundwater and the fourth-largest groundwater withdrawing country. The Indus Basin aquifer from where Pakistan withdraws its groundwater has become the world’s most “overstressed” groundwater aquifer. Given the growing shortages of surface and groundwater, the informal groundwater markets where farmers trade water have emerged in all provinces of Pakistan. Despite the considerable attention paid to the analysis of water markets in several countries, there is little evidence on the structure and implications of contractual agreements between the water users. This study includes buyers’ bargaining power in the contract choice model to estimate unbiased determinants of contract choice. The data was collected through a comprehensive survey of Punjab’s groundwater markets. Using several descriptive and econometric approaches, we find that the water markets in Pakistan are relatively competitive. A flat-rate water marketing contract is common in water-scarce regions, while a fuel-based contract is common in areas with large farmers. We find that buyers’ bargaining power is primarily determined by an agent’s ability to influence a joint decision between buyers and sellers. In addition, a seller’s landholding size also influences the choice of contract, as fuel-based contracts are more likely to be offered to large farmers. The relative bargaining power of buyers influences choice of fuel-based contracts, although this offers lower profits to sellers. We find evidence of price discrimination in which relatively well-off buyers with a long contractual history with sellers may receive discounts in the form of fuel-based contracts. As contract choice may also determine the extent of water use, these findings have implications for environmental sustainability. Policy intervention to standardize groundwater marketing contracts can help reduce overexploitation of groundwater and environmental externalities and promote sustainable development.

Semen stain is one of the most important biological evidence at sexual crime scenes. Age estimation of human semen stains plays an important role in forensic work, and it is rarely studied due to lack of well-established methods. In this study, the technique called attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) coupled with advanced chemometric methods was employed to determine the age of semen stains on three different substrates: glass slides, tissues and fabric made of regenerated cellulose fibres up to 6 d. Partial least squares regression (PLSR) was used in conjunction with spectral analysis for age estimation, and the results generated high R2 values (cross-validation: 0.81, external validation: 0.74) but a narrow margin of error for root mean square error (RMSE) (RMSE of cross-validation: 0.77 d, RMSE of prediction: 1.02 d). Additionally, our results indicated the robustness of PLSR model was not weaken by the influence of different substrates in this study. Our results indicate that ATR-FTIR, combined with chemometric methods, shows great potential as a convenient and efficient tool for age estimation of semen stains. Moreover, the method could be applied to routine forensic investigations in the future.

The Qinghai–Tibet Plateau is sparsely populated and has vast grassland, which plays an important role in the development of animal husbandry. However, during the forage cutting season, frequent rainfall and low temperatures are consistently experienced, which makes it extremely difficult to produce quality hay. The best way to process hay is to produce silages. In this experiment, dry matter yield and silage fermentation quality of dominant annual forages, namely triticale, rye and oat, with Sila-Max and Sila-Mix lactic acid bacteria additives at the five cutting stages, i.e., heading, flowering, grouting, milky and dough stages, were determined. Triticale at the dough stage had the highest dry matter yield among the three forages at the five cutting stages. The optimum harvesting time for triticale, rye and oat to produce quality silage in the Qinghai–Tibet alpine area was the milky stage. Sila-Max lactic acid bacteria additives could significantly improve the fermentation qualities of triticale, rye and oat silages, but the fermentation effect of Sila-Mix on the three silages was not significant. The triticale variety ‘Gannong No.2’ is the best raw material to produce quality silages in the Qinghai–Tibet alpine area. Overall, quality silage could be made in the Qinghai–Tibet alpine area while using the triticale variety ‘Gannong No.2’ as the raw material, cutting it at the milky stage and adding Sila-Max as the lactic acid bacteria additive.

The combination of Herba Ephedrae (Mahuang in Chinese) and Radix Aconiti Lateralis (Fuzi in Chinese) is a classical preparation in traditional Chinese medicine and used for treating colds and rheumatic arthralgia. However, herbal medicines containing ephedrines and Aconitum alkaloids are strictly regulated because of the potential for adverse effects on the cardiovascular system and the central nervous system. We aimed to investigate the pharmacokinetics of 11 alkaloids in the Mahuang-Fuzi combination and single-herb extracts after oral administration in rats. The alkaloids were norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine. Simultaneous determination of the alkaloids, including two pairs of diastereomers, was achieved in 14.5 min by a simple, rapid and sensitive ultra-performance liquid chromatography–tandem mass spectrometry method. The separation was performed on a Zorbax SB-Aq column (100 mm × 2.1 mm, 3.5 μm) at a flow rate of 0.3 mL/min using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. The validated method demonstrated adequate sensitivity, selectivity and process efficiency for the quantitative analysis of complex herbal components. Compared with single-herb extracts, alkaloids in plasma (except methylephedrine, benzoylmesaconine and benzoylhypaconine) showed slower elimination (the mean residence time or half-life was longer), although the maximum plasma concentration and area under the plasma concentration curve values decreased. Accumulation may occur with continuous drug intake. These results suggest that drug monitoring may be essential for the safe use of the Mahuang-Fuzi combination. [ABSTRACT FROM AUTHOR]

Abstract Estimation of the age of human bloodstains is of great importance in forensic practices, but it is a challenging task because of the lack of a well-accepted, reliable, and established method. Here, the attenuated total reflection (ATR)-Fourier transform infrared (FTIR) technique combined with advanced chemometric methods was utilized to determine the age of indoor and outdoor bloodstains up to 107 days. The bloodstain storage conditions mimicked crime scene scenarios as closely as possible. Two partial least squares regression models—indoor and outdoor models with 7–85 days—exhibited good performance for external validation, with low values of predictive root mean squared error (5.83 and 4.77) and high R2 values (0.94 and 0.96) and residual predictive deviation (4.08 and 5.14), respectively. Two partial least squares–discriminant analysis classification models were built and demonstrated excellent distinction between fresh (age ≤1 d) and older (age >1 d) bloodstains, which is highly valuable for forensic investigations. These findings demonstrate that ATR-FTIR spectroscopy coupled with advanced chemometric methods can be employed as a rapid and non-destructive tool for age estimation of bloodstains in real-world forensic investigation.

Estimating PMI is of great importance in forensic investigations. Although many methods are used to estimate the PMI, a few investigations focus on the postmortem redistribution. In this study, ultraviolet-visible (UV-Vis) measurement combined with visual inspection indicated a regular diffusion of hemoglobin into plasma after death showing the redistribution of postmortem components in blood. Thereafter, attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy was used to confirm the variations caused by this phenomenon. First, full-spectrum partial least-squares (PLS) and genetic algorithm combined with PLS (GA-PLS) models were constructed to predict the PMI. The performance of GA-PLS model was better than that of full-spectrum PLS model based on its root mean square error (RMSE) of cross-validation of 3.46 h (R2 = 0.95) and the RMSE of prediction of 3.46 h (R2 = 0.94). The investigation on the similarity of spectra between blood plasma and formed elements also supported the role of redistribution of components in spectral changes in postmortem plasma. These results demonstrated that ATR-FTIR spectroscopy coupled with the advanced mathematical methods could serve as a convenient and reliable tool to study the redistribution of postmortem components and estimate the PMI.

In forensic practice, determination of electrocution as a cause of death usually depends on the conventional histological examination of electrical mark in the body skin, but the limitation of this method includes subjective bias by different forensic pathologists, especially for identifying suspicious electrical mark. The aim of our work is to introduce Fourier transform infrared (FTIR) spectroscopy in combination with chemometrics as a complementary tool for providing an relatively objective diagnosis. The results of principle component analysis (PCA) showed that there were significant differences of protein structural profile between electrical mark and normal skin in terms of α-helix, antiparallel β-sheet and β-sheet content. Then a partial least square (PLS) model was established based on this spectral dataset and used to discriminate electrical mark from normal skin areas in independent tissue sections as revealed by color-coded digital maps, making the visualization of electrical injury more intuitively. Our pilot study demonstrates the potential of FTIR spectroscopy as a complementary tool for diagnosis of electrical mark.