This study applied network analysis to explore the relations between neuropsychological functions of individuals in the clinical evaluation of attention-deficit/hyperactivity disorder (ADHD) in adulthood. A total of 319 participants from an outpatient referral context, that is, 173 individuals with ADHD (ADHD group) and 146 individuals without ADHD (n-ADHD group), took part in this study and completed a comprehensive neuropsychological assessment. A denser network with stronger global connectivity was observed in the ADHD group compared to the n-ADHD group. The strongest connections were consistent in both networks, that is, the connections between selective attention and vigilance, and connections between processing speed, fluency, and flexibility. Further centrality estimation revealed attention-related variables to have the highest expected influence in both networks. The observed relationships between neuropsychological functions, and the high centrality of attention, may help identify neuropsychological profiles that are specific to ADHD and optimize neuropsychological assessment and treatment planning of individuals with cognitive impairment. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder, characterized by symptoms of inattention, hyperactivity, and impulsivity . Up to 5Numerous neuropsychological studies demonstrated that adults with ADHD commonly present with impairments in multiple cognitive functions, including processing speed , selectiAn analytic technique for exploring the relationships between different variables, known as network analysis, may be a suitable approach to provide new insight into the picture of intertwined cognitive functions in adult ADHD. Compared to more traditional statistical approaches, such as univariate or multivariate group comparisons and correlation matrices, network analysis considers all variables for drawing a complex network that visually depicts the interrelations between variables. A network consists of nodes representing any conceivable variables  and edges connecting these nodes which represent any conceivable relationship  . NetworkThis study is, to our knowledge, the first to apply network analysis on neuropsychological functions (performance test variables) of a large sample of clinically referred individuals at an ADHD outpatient clinic. The goal of this study is to examine the potential relationship between various aspects of cognitive functions of individuals diagnosed with or without ADHD. Specifically, this study aims to (a) explore the potential relationships between different cognitive functions of individuals diagnosed with ADHD as well as individuals who did not meet the diagnostic criteria of ADHD and whether there is a specific network structure for the ADHD group, which may have the potential to define ADHD-specific cognitive profiles. Moreover, this study aims to (b) define the centrality of cognitive functions, which is characterized by strong connections to numerous other cognitive functions. Central cognitive functions have the potential to be the primary targets of treatment to effectively improve the functioning of adults with ADHD.Diagnostic and Statistical Manual of Mental Disorders , a neurological condition , or a condition affecting the ability to perform cognitive tests . Finally, a total of 319 participants were included in the data analysis, of which 173 participants received a diagnosis of ADHD after a comprehensive evaluation  and 146 participants who did not meet the diagnostic criteria of ADHD . In the n-ADHD group, 92 of the 146 participants did not reach diagnostic criteria of any psychiatric disorder, whereas 54 participants showed evidence for one or more other psychiatric disorders other than ADHD, including mood disorders (n = 34), personality disorders (n = 8), addiction disorders (n = 6), anxiety disorders (n = 4), adjustment disorders (n = 2), posttraumatic stress disorders (n = 2), eating disorders (n = 2), autistic disorders (n = 1), schizophrenia (n = 1), and somatization disorder (n = 1). In the ADHD group, 149 individuals were diagnosed with the predominantly combined symptom presentation, 23 individuals with the predominantly inattentive symptom presentation, and one individual with the predominantly hyperactive/impulsive presentation. Furthermore, 46 of the 173 patients with ADHD were additionally diagnosed with one or more comorbid psychiatric disorders (see n = 27), addiction disorders (n = 11), personality disorders (n = 8), anxiety disorders (n = 6), adjustment disorders (n = 5), autistic disorders (n = 2), oppositional defiant disorders (n = 1), and posttraumatic stress disorders (n = 1). The observation that the distribution of psychiatric conditions other than ADHD was comparable and nonsignificantly different between the ADHD and the n-ADHD group (see t (283) = −1.780, p = .076, sex ratio, χ2 (1) = 3.781, p = .052, and education level, χ2(4) = 8.570, p = .073. As expected, patients with ADHD scored significantly higher in both current self-reported ADHD symptoms, t (299) = 3.398, p = .001, and retrospective self-reported ADHD symptoms for childhood, t (298) = 7.223, p < .001. However, no significant group difference was observed in self-reported cognitive functioning, t (313) = 1.922, p = .056.A total of 332 participants agreed to take part in this study; however, 13 of 332 participants were excluded from the data analysis. Eight participants were excluded because they were currently treated with psychostimulants at the time of the assessment. Another five participants were excluded as they were considered as not representative of this population, that is, individuals with mental disability  was used to retrospectively assess ADHD symptoms in childhood . A totalA computerized neuropsychological test battery for the assessment of cognitive functions in adult ADHD CFADHD;  of the VThe Perceptual and Attention Functions—selective attention WAFS;  was usedVigilance was assessed with the Perceptual and Attention Functions—vigilance WAFV; . In thisWorking memory was measured with the 2-back design of the NBV  of the main variables was reported to be 0.97.Interference control was assessed with the Stroop Interference Test , which wThe Trail-Making Test—Langensteinbach Version TMT-L;  was usedThe Tower of London—Freiburg Version TOL-F;  was admiThe Go/No-Go test paradigm  was usedtask switching accuracy, which was the difference between the percentage of correct responses for switching and repeated tasks. The internal consistency (greatest lower bound) of this variable was satisfactory and reported to be 0.81.Task switching was measured with the SWITCH . In thisDescriptive statistics and inferential group comparisons were computed using IBM SPSS (Version 25.0 for Windows). Network analyses of neuropsychological functions were performed with RStudio .U tests). To control for alpha error growth in multiple testing, a stringent significance level of p < .01 was applied. Finally, the magnitude of group differences was indicated by the effect size Cohen’s r, with r = 0.1 indicating a small effect, r = 0.3 indicating a medium effect, and r = 0.5 indicating a large effect (The Median and interquartile range (IQR) of each test variable, as well as the percentage of individuals showing impairment in each of the neuropsychological functions, are presented in descriptive statistics. The interpretation of test data was based on norm scores provided by the test publisher. Impairment was defined if a test variable indicated a score equal to or below the 16th percentile  of the respective normative group . Furthere effect .bootnet and qgraph (λ), which can be determined using the Extended Bayesian Information Criterion (EBIC)  . The visn (EBIC) . In the n groups . As our n groups  was perfcentrality, centralityTable, and centralityPlot function of qgraph package was used to compute and plot the expected influence  of the edge weights, with smaller CIs indicating higher accuracy of the order of most edges in the network. Node centrality stability was estimated using the correlation stability coefficient (CS coefficient). Based on the simulation design of NetworkComparisonTest was used for these comparisons , which is a statistical testing procedure for network comparison, was used to perform these comparisons . NCT comparisons .Z-scores per neuropsychological function. Finally, considering the nearly significant sex difference between the ADHD and n-ADHD group (p = .052), additional network analyses were carried out to examine the potential influence of sex.First, additional network analysis was performed on the individuals with the combined symptom presentation only to examine the potential influence of different symptom presentations of ADHD. Second, to address the possibility that different weights for each test  may bias our findings, additional network analysis was performed based on averaged p = .003), as individuals in the ADHD group made significantly more omissions errors than the n-ADHD group as shown in a small effect of Cohen’s r = 0.16. Per neuropsychological function, the largest impairment rates were found in vigilance , selective attention (55.2% and 55.5%), response inhibition (45.9% and 40.3%), and interference control (40.7% and 39.6%). Impairment in a given function is defined if impairment was observed in at least one test variable of this function.Descriptive statistics and group comparisons of neuropsychological test performance for the ADHD and n-ADHD groups are presented in n-ADHD network has few connections and most of the connections are weak. But the strongest connections appear to be consistent between these two networks, including the connections between two attention tests, that is, selective attention test and vigilance test , as well as the connection between two variables stemming from the Trail-Making Test (10 and 14). Furthermore, connections between all variables of attention  and connections between figural fluency, cognitive flexibility, and processing speed  were also observed in both the ADHD and n-ADHD networks. In addition, the connection between selective attention and working memory (3 and 6) as well as the connection between vigilance and response inhibition (4 and 12) was observed in the ADHD network. Compared to other variables, task switching (13) is relatively isolated in the ADHD network.The visualized networks of the ADHD and n-ADHD groups are presented in Node centrality estimations are presented in Figures S1 and S2 in Supplemental Material). The node centrality estimation revealed that the CS coefficients were 0.36 (ADHD) and 0.44 (n-ADHD), indicating that the orders of node centrality were stable.The edge weight accuracy estimation revealed moderate CIs and indicated that the orders of edge weights were accurately estimated in both the ADHD network and the n-ADHD network .The visual comparison suggests denser and stronger connections in the ADHD network than in the n-ADHD network. Further NCT analysis indicates that the global connectivity strength of the ADHD network is significantly stronger than that of the n-ADHD network  and connections between measures of processing speed, flexibility, and fluency . The connections between selective attention and vigilance add evidence to the argument that different attention components are related in terms of behavioral performance as well as its neural basis . The corOther than these consistent connections, most variables in the ADHD network were weakly or moderately correlated with each other, such as working memory, planning, response inhibition, and interference control. The position of these functions in the network is partly consistent with earlier findings that children with ADHD show deficits in several relatively independent neuropsychological functions, including working memory, inhibition, and response variability , which hMoreover, the highest expected influence of attention-related variables  in both the ADHD and the n-ADHD network stresses the central role of attention for a broad range of other neuropsychological functions. High expected influence of attention observed in this study provides new empirical evidence to the argument that basic cognitive functions are significantly associated with and contribute to the higher-order cognitive functions as suggested in numerous studies . On the Z-scores per neuropsychological function. Results were comparable to our initial analysis, such as the strong connection between selective attention and vigilance, the strong connection between processing speed/flexibility and fluency, and the highest expected influence of selective attention and vigilance. These results support the reliability of our initial analysis based on multiple test scores per function . Finally, considering the nearly significant sex difference between the ADHD and n-ADHD group (p = .052), additional network analyses were carried out to examine the potential influence of sex . These additional analyses revealed no significant differences in global connectivity strength by sex, neither in the ADHD nor the n-ADHD group. Selective attention and vigilance still have the highest expected influence in the male and female networks within both the ADHD and n-ADHD groups. However, we noted that variables of selective attention  have a seemingly higher expected influence in the male n-ADHD network compared to the female n-ADHD network, which needs replication on larger samples in future studies.Furthermore, to address the possibility that different weights for each test  may bias the findings of centrality estimation, additional network analysis was performed based on averaged Figures S9 and S10 of the Supplemental Material) and revealed no meaningful differences compared to the analysis of the entire group of patients with ADHD. Even though this study gives no indication for bias by ADHD subtype, future studies are needed on large samples of ADHD with sufficiently large numbers of the various ADHD symptom presentations to address this issue properly. Fourth, potential cognitive subtypes proposed in previous research (e.g., Several limitations of this study should be taken into account. First, effect sizes of network analyses cannot be calculated based on current statistical methodology. The magnitude of the findings, for example, to compare global connectivity or expected influence, would benefit the interpretation of the findings and their clinical implications. Second, it must be stressed that networks do not indicate causal relationships between functions. Even though “expected influence” may appear like directional paths, no such causal relationships can be inferred from networks . Third, ch e.g.,  may alsoThis study is the first using network analysis to investigate the relationship between various neuropsychological functions in a large sample of clinically referred individuals at an ADHD outpatient clinic. Further strengths of this study are that it uses a naturalistic design, using data derived from the routine clinical practice of an ADHD clinic, as well as a clinical comparison group with similar characteristics in key clinical features which increases ecological validity. Network estimations and comparison revealed a denser and significantly stronger network of neuropsychological functions in the ADHD group compared to the n-ADHD group. The stronger and more interrelated network of neuropsychological functions observed in individuals with ADHD may be a starting point to identifying intertwined neuropsychological characteristics that are typical for ADHD. Furthermore, among the broad range of neuropsychological functions assessed, attention performance displayed the highest expected influence on other neuropsychological functions in both the ADHD and the n-ADHD network, which provides clinically relevant implications for the clinical assessment, treatment planning, and treatment evaluation of individuals with cognitive impairment.Click here for additional data file.Supplemental material, sj-docx-1-asm-10.1177_10731911221118673 for Networks of Neuropsychological Functions in the Clinical Evaluation of Adult ADHD by Nana Guo, Anselm B. M. Fuermaier, Janneke Koerts, Oliver Tucha, Norbert Scherbaum and Bernhard W. Müller in Assessment


Fast progress in near-net-shape production of parts has attracted vast interest in internal surface finishing. Interest in designing a modern finishing machine to cover the different shapes of workpieces with different materials has risen recently, and the current state of technology cannot satisfy the high requirements for finishing internal channels in metal-additive-manufactured parts. Therefore, in this work, an effort has been made to close the current gaps. This literature review aims to trace the development of different non-traditional internal surface finishing methods. For this reason, attention is focused on the working principles, capabilities, and limitations of the most applicable processes, such as internal magnetic abrasive finishing, abrasive flow machining, fluidized bed machining, cavitation abrasive finishing, and electrochemical machining. Thereafter, a comparison is presented based on which models were surveyed in detail, with particular attention to their specifications and methods. The assessment is measured by seven key features, with two selected methods deciding their value for a proper hybrid machine.  After presenting a new method of fabrication for three-dimensional plastic models by Kodama in 1981, several different layered manufacturing techniques have been developed . After tAccording to ISO/ASTM 52900:2015 (E), additive manufacturing (AM) is a process of joining materials to make parts from 3D model data, usually layer upon layer, instead of subtractive manufacturing and formative methodologies . In the Nonetheless, even the internal surface finishing is difficult due to the limitations of reaching the internal parts and holes of the products. Conventional machining methods like grinding, honing, and lapping are unsuitable for internal surface finishing because they are time-consuming, labor-intensive, low quality, and have geometrical limitations . Thus, iASTM Committee F42 on Additive Manufacturing Technologies has been active since 2009 and is composed of subcommittees addressing specific segments such as materials and processes, design, test methods, and so on. The purpose of the committee is the promotion of knowledge, stimulation of research, and implementation of technology through the development of standards for additive manufacturing technologies. These standards are expected to play a significant role in all aspects of additive manufacturing technologies. As shown in Ra) of less than one micron before they are used in practical applications [The roughness of a surface is affected by various process parameters, such as the energy source, scan speed, scan pattern, hatch spacing, build orientation, and channel diameter. The side surface roughness is less affected by process factors than the top surface roughness, and optimization rarely reduces the side surface roughness. Even with the best process factors, AM components have linear surface roughnesses in the 5 to 15 μm range ,20. It iications ,22. Usinications . Howeverications  employedications .Nowadays, the need for precise internal surface finishing attracts enormous interest from researchers to contribute to developing innovative and hybrid methods for complex shapes ,26. For The objective of this paper titled is to provide a comprehensive review of the current state of research and development in the field of internal surface finishing of metallic components produced using additive manufacturing (AM) techniques. This paper aims to highlight the recent progress and advances in various methods and techniques used for the internal surface finishing of AM metallic components. Far too little attention has been paid to comparing the available methods and prioritizing them according to their efficiency, cost, part size limitation, and material limitation. Hence, in this work, the authors address the practical results of different surface finishing methods, such as magnetic abrasive finishing, abrasive flow machining, fluidized bed machining, cavitation abrasive finishing, and electrochemical machining, considering the recent outcomes. Regarding the methodology, the scope of this paper, compared to previous reviews, is brought up with more comprehensive frontier models since the authors aim predict which models could combine in the right way. To this aim, first, a specific domain of models in the literature has been reviewed. These features are directly extracted from the literature and represent common surface finishing challenges. Finally, a score-based comparison is presented as a novel work to rank the priorities and define the combined system. In addition, this paper identifies the challenges and opportunities for further research and development.(I)Problem definition through state-of-the-art analysis of the achieved surface characteristics of the as-built parts through the metal AM processes and related internal surface finishing techniques;(II)Considering the table of contents of several significant journals from 2005 to early 2023;(III)Verifying the reference list of highly cited papers based on keywords;(IV)Surveying the publications of outstanding scholars within surface finishing methods to find the most influential papers in this area.A multi-layer chain in These four steps have given a superset of more than 100 papers, further filtered for relevance to internal surface finishing. Building on this paper repository, a literature review is implemented in the third echelon, along which the articles are investigated in detail through the five key issues. The aim is to recognize a set of criteria that can confirm the possibility of process combination for obtaining the best possible surface roughness in complex-shaped components with different materials.In the PBF process, the components must be oriented between ±90° with respect to the building plate, forming surfaces with different qualities. It is well documented that poor surface roughness and inaccurate internal channels are two inherent features of additively manufactured components ,32,33. TAs shown in Conventional finishing processes refer to the traditional methods of surface finishing that have been used for many years in manufacturing. These processes are typically mechanical, such as grinding, sanding, and polishing. Grinding is a process in which an abrasive material, such as a grinding wheel or belt, is used to remove material from the surface of a part or component. This process is often used to achieve a smooth, uniform surface finish or to remove any unwanted material or defects from the surface . SandingNon-conventional surface finishing is a crucial post-processing step in producing complex shape components with internal channels. The internal surface roughness can affect the dimensional accuracy of the channels and flow characteristics during flow transportation. To date, several studies have proposed different types of surface finishing that can be applied in finishing the internal surfaces of the channels and tubes. For instance, the magnetic abrasive finishing (MAF) method has been introduced by Shinmura et al. to finish the internal surface of stainless tubes . Kim et On the other hand, the necessity of finishing different kinds of internal channels has forced researchers to find other solutions. According to the literature, the most well-known and feasible methods that can be used to finish the surface of internal passages in the complex-shaped components are abrasive flow-based, magnetic abrasive-based, fluidized-based, cavitation-based, and electrochemical-based finishing . Thus, tAFF or AFM, developed explicitly for internal surface finishing, is a new method to achieve high precision on the internal surface and can reach a roughness of 0.2 μm or less . In the In this technique, silicon carbide or alumina usually is used as the abrasive material, whereas polyborosilixane is employed as the noncorrosive medium to finish the surface. Micro-cutting and micro-ploughing are two main material removal mechanisms in the AFM method that results in a surface finish in the range of micrometers to nanometers . The floThe material removal rate depends on several factors: media flow rate, viscosity, abrasive particle size, abrasive concentration, particle density, particle hardness, and workpiece hardness. Nevertheless, AFM can be applied to various metals such as titanium, superalloys, and hardened and difficult-to-machine materials ,60. For Recently, Hashmi et al.  examinedIn another work by Basha et al. , an alte2O3, SiC, and B2O3 particles and different temperature ranges on maraging steel’s roughness and wear properties. The findings showed that the media containing Al2O3 particles led to a surface with higher roughness than other media. In addition, the variation of surface roughness at different temperatures can be observed in Seyedi et al.  employedHowever, it is reported that very high pressures of abrasive flow (>220 bar) inside the channels damage the surface of the thin-walled channels. Therefore, it is necessary to control the pressure of the abrasive flow inside the channels and control the cutting forces during the finish operation. For this reason, magnetic-based AFM methods have been developed and introduced. Magnetic-assisted AFM (MAAFM) and magnetorheological abrasive flow finishing (MRAFF) are examples of these magnetic-based AFM methods ,67. In fIn general, in MAAFM, applying a magnetic field makes it possible to pull the abrasive media that includes ferromagnetic abrasive particles to the sides, consequently enhancing the number of active abrasive grains. Instead, in MRAFF, a magnetorheological fluid is mixed with abrasive particles and then dispersed in a nanomagnetic carrier. When a magnetic field is applied, the rheology of this fluid changes and facilitates the control of finishing forces.Ra) and material removal rate (MMR) of an Al/SiC/B4C hybrid metal matrix composite. According to the results, MRR and ∆Ra significantly increased with an increase in extrusion pressure , while with a decrease in mesh number, MRR and ∆Ra improved by 14.56% and 22.58%, respectively. With increased abrasive concentration, the roughness decreases by 8.18%. On the other hand, a rise of 13.5% in MRR resulted from an increase in magnetic flux density.Chawla et al.  developeRa of 54.42% were achieved.Further developments arrived at ultrasonic-assisted AFM (UAAFM) that integrates ultrasonic energy with AFM. In this finishing, ultrasonic vibration is applied to the pressurized abrasive flow before reaching the internal channel. In this way, it is possible to increase the interaction forces between the abrasive grains and the surface of the internal channel and, as a result, improve the efficiency of the finishing operation ,70. ChooThrough the comparison between different AFM, it can be concluded that the rheological characteristics of the abrasive media are critical. Thus, several researchers have been developing new abrasive media that can enhance the quality of AFM. Nonetheless, despite several efforts that have been made on AFM, several limitations still exist. For instance, blind holes are still challenging to be machined through AFM technology. Furthermore, fluid flow characteristics of the abrasive media are another limitation that makes the uniform finishing operation very difficult. Finally, contamination problems due to the abrasive particle’s embodiment onto the surface of the workpiece are another challenge in AFM.The second non-traditional finishing method is MAF, which has high precision. In this method, a magnetic field controls the finishing forces during the finishing operation . This me2O3 with some ferromagnetic particles [To avoid the excessive frictional force of the particles on the internal surfaces, a lubricant such as oil is also fed into the channel during the finishing operation. Since in the MAF process, the finishing operation is carried out using an external electromagnetic field on the abrasive particles to guide them into the finishing area; the abrasive particles should have high magnetic susceptibility in addition to their abrasive characteristics. In this way, under the electromagnetic field, magnetic forces are formed and penetrate the abrasive particles onto the surface of the channel. For this reason, the abrasive particles in this method are conglomerates containing a highly magnetic-susceptible material, like iron, and hard abrasive material, like nano alumina. Magnetic abrasives, such as hard iron alloys, are usually used to finish soft or non-ferrous metals . Insteadarticles . In addiarticles ,80. Accoarticles ,82. RegaRa of the surface up to 76%. Recently, Guo et al. [After applying the electromagnetic field and penetration of abrasive particles into the internal surfaces, through the fast rotation of the sample or magnetic pole system it would be possible to create a motion between the abrasive particles and internal surfaces and, consequently, remove the material in the form of fine abrasion. It is well documented that this method can finish external and internal surfaces to obtain surface roughness down to a few nanometers. For instance, Zhang et al.  used MAFo et al.  investigRa from 7.22 μm to 0.51 μm, 0.36 μm, and 0.23 after polishing using rotation motion, vibration, and integration, respectively  can be achieved using 35 mm, 430 rpm, and 2 min as the working gap, rotational speed, and machining time, respectively. In another work, Aizawa et al. [Saxena et al.  studied a et al.  studied Zhu et al.  used sphIn the two similar works by Zhao et al. and Li et al., the effect of MAF and heat treatment conditions on the microstructure of additively manufactured Inconel 718 super-alloys was studied ,88. The Another critical factor in this technology is the relative hardness of the component concerning the abrasive particles that determine the depth of cut obtained by the abrasive particles. As mentioned earlier, since in this technology the material removal is carried out by a magnetic field, it implies that the strength of the magnetic field, which is adjusted by the distance between the yoke and the part, plays a key role. The influence of this aspect would be more important in the case of bend tubes or internal channels where different finishing forces are required at inner and outer radii zones . MAF’s tApart from the experimental investigation, several efforts based on simulation and modeling have been made on this technology ,91. For Ra, it has been found that internal surface finishing of channels with a diameter less than 1 mm is still challenging [Despite the successful finishing of various AM parts made of different materials such as AlSi10Mg, Ti6Al4V, Inconel 625, and Inconel 718 alloys, reaching 0.21 μm for llenging ,94,95. BFBM is an advanced surface finishing method that uses fluid bed hydrodynamics to finish the surface . This meIn addition to the abrasive and workpiece characteristics, fluidization property is the critical factor that defines the capability and efficiency of the process in both FBM and FB-AJM processes. It is reported that if the feeding of abrasives into the internal channel can be automatically reversed through the fluidized beds, a uniform surface can be obtained afterward. The basic machining is done through jetting, whereas the fluid beds increase the machining efficiency, reproducibility, and surface quality. For instance, it is reported that at a minimum fluidization region, since the weight of abrasive particles counterbalances the hydrodynamic push, the abrasive bed starts to transit between a fixed bed and a bubbling bed . By incrRz, which is the arithmetic height of the profile, from 40 μm to 5–7.5 μm after just four machining cycles. Another advantage of FBM and FB-AJM is their independence from the initial surface roughness, and the finishing operation time depends on the abrasive size. Another critical parameter is workpiece rotation speed and abrasive impact velocity. Nevertheless, it should be underlined that these two technologies face several challenges, such as abrasive contamination of soft workpieces, difficulty in the surface finishing of the linear channels, and longer diameters [Overall, these two processes have a high potential for fine finishing operations in such a way that through these processes it would be possible to finish the surface to lower than 0.4 μm. For example, FBM has been used for the surface finishing of narrow and long tubes made of aluminum  and staiiameters . OverallAtzeni et al.  studied Sahu et al.  worked oCavitation abrasive finishing has great potential for the surface finishing of AM parts ,107. In Ra = 20 µm, and Rz > 100 µm). They found that by using the HCAF process, it would be possible to improve the surface texture (up to 90%) and, after a 150 min finishing operation, reach a surface with a very low surface roughness   was introduced by Nagalingam et al. as a reliable method for the surface finishing of the internal channels . Yeo and= 30 µm) .Ra, Sa < 1 μm and Rz < 20 μm). They showed that when the micro-abrasives are used in the working fluid, the random surface asperities are removed gradually, resulting in surface erosion  and anodic etching (micro-smoothing) in ECP/ECF . In macrA combination of electrochemical machining (ECM) and MAF is a more productive process called electrochemical magnetic abrasive finishing (EMAF). This process has higher efficiency with respect to the single MAF or ECM, and the abrasives could be protected ,143. ThiAnother type of electrochemical finishing process is ultrasonic vibration electrochemical finishing. The ultrasonic vibration process primarily aims to effectively discharge electrolytes and by-products in ECF/ECP. Experimental results show that ultrasonic vibrations can give 21–44% improvement in surface finish, depending upon the process variants and conditions used. The use of ultrasonic energy began in 1927 to produce holes in a glass bar. Later, the process improved for welding, metallurgy, and cleaning processes. Likewise, it has been used in electrochemical finishing processes to enhance surface finish ,146,147.Zhu et al.  combinedJiang et al.  investig2. By contrast, the workpiece surface showed uneven surface and pitting corrosion when the current density was 10 A/cm2. To ensure the quality, efficiency, and stability of ECMs, a high current density of more than 20 A/cm2 is recommended [ommended . The homSurface finishing has always been a central issue in engineering, and researchers have often attempted to provide tools, sometimes very sophisticated, to develop the processes dynamically. This stream of research has been accelerating for the past decade, perhaps due to the increasing levels of manufacturing and its complexity, such as additive manufacturing. From a managerial point of view, advanced manufacturing, although providing many benefits to the development of products, has brought more demands on surface finishing. Regarding these demands, several methods have been developed in five primary categories, which are abrasive flow finishing (AFF), magnetic abrasive finishing (MAF), abrasive fluidized bed machining (AFB), cavitation abrasive finishing (CAF), and electrochemical finishing (ECF).(I)The review addresses only the recent advances in process modeling. This focus distinguishes it from most of the contributions in the literature from the timescale perspective;(II)The review covers different methods in surface finishing, while the other reviews focused on each one separately;(III)The outcome of the models is considered here but with a comparison among all five so-called techniques.Three key elements have characterized the focus of this review:This section is structured in a detailed survey of models to study the recent advances in the internal surface finishing of complex-shaped components for good orientation in further steps. Our review is accomplished through the six critical issues on the internal surface finishing: component materials and shape, apparatus requirements, roughness change, limitation, internal surface accessibility, and post/pre-processing conditions. In this section, different methods for surface finishing are analyzed based on the seven most critical factors and their accordance values. In this regard, each technique has its score for post-processing and pre-processing, and the scoring in Roughness improvement: Regarding the primary goal of surface finishing, material removal and roughness improvement are among the most important factors in all considerations. The roughness improvement score is 20% of the total.Internal surface finishing: Inevitably, accessibility for internal surface finishing is important for industrial components. Internal surface finishing score is 10% of the total. It should be noted that roughness improvement and internal surface finishing are both related to surface quality, but they differ in their focus and methods. Roughness improvement is primarily concerned with reducing the surface roughness of a material to achieve a smooth and uniform surface finish, while internal surface finishing is concerned with improving the quality and cleanliness of the internal surface of a material to optimize its performance and functionality.Size of components: In industries, parts are made in different sizes, and all machines and tools must be more flexible for different scales. The size of the components score is 10% of the total.Complex-shaped components: Surface finishing in complex-shaped workpieces is needed by the state-of-the-art finishing methods. Complex-shaped components score is 20% of the total.Possibility of finishing the Al and Ti products: Nowadays, Al and Ti components are expanding, and it seems essential to consider their consequences for surface finishing. The possibility of finishing the Al and Ti products score is 10% of the total.Cost of operation: Cost is an important index in all engineering activities. Costs of operation can be estimated by the features and complexities of the apparatus for each specific method. The cost of operation score is 10% of the total.Post- and pre-processing scores: For the best possible hybrid system, defining the best pre-processing and post-processing methods is crucial. In this regard, all methods are ranked as their ability for post- and pre-processing, and each of these numbers is influenced by the related final score for the post- and pre-processing, respectively.Post- and pre-processing scores have percentages of 20% of the total separately.Seven different criteria are used to shape the comparison:The measurement of hidden surface roughness will be challenging and require a custom solution for each AM component. Furthermore, in order to enhance the functionalities of AM components, surface finishing activities will also include applying various coatings on hidden and internal surfaces. A new frontier of research is emerging due to the unique geometry of AM components for targeted application areas. For example, electroless nickel coating processes  and atomThe use of non-contact or non-destructive methods for surface finishing of additively manufactured metallic components is another exciting future direction. These methods could include techniques such as plasma polishing or ultrasonic vibration, which could potentially offer advantages such as greater precision, reduced material removal, and faster processing times.Future research could also investigate the potential for combining multiple finishing processes to achieve a more optimized surface finish. For example, a combination of mechanical and chemical finishing processes may be more effective at achieving a specific surface finish than either method used alone.(1)Since AM with poor surface finishing will fail prematurely in corrosive environments and cyclic loading, their internal surface finishing is the bottleneck preventing innovatively designed components from being applied in the intended environments.(2)All non-traditional finishing processes discussed in this review have been successfully applied to a wide range of additively manufactured materials with low values of surface roughness. Nevertheless, based on the literature, ECM and CAF have shown an average reduction in roughness percentage of around 60–70%, but an improvement of more than 90% has been obtained for AFM and AFB.(3)Both interior and exterior surfaces of AM metals can be polished with abrasive processes, which can be applied in rigid forms or in fluidized media. Abrasive finishing techniques lead to the reduction of surface roughness and create beneficial compressive residual stresses. In order to polish AM metals with common shapes, abrasive particles can be combined with magnetized particles added to ultrasonic cavitation.(4)The choice of the most applicable internal surface finishing method for AM materials will depend on the specific requirements of the part and the desired end-use application. For example, the ECP process is the most promising for complex geometries and porous lattice structures.(5)Through various reviewed methods and techniques, it has been found that the suitable combination of further studies could be EMAF for pre-processing and fluidized beds to a FB-AJM for post-processing.(6)This paper provides a valuable resource for researchers and practitioners in AM, highlighting the importance of internal surface finish and the various methods and innovations available to achieve it.(7)Despite many advantages offered by different advanced finishing processes, there are still limitations like size-limited processes, expensive operation, difficult finishing complex-shape components, and time-consuming processes, especially for large workpieces.


Radiotherapy (RT) is one of the most mainstream cancer therapeutic modalities. However, due to the lack of specificity of the radiation adopted, both normal and cancerous cells are destroyed indiscriminately. This highlights the crucial need to improve radiosensitization. This study aims to address this issue by constructing a multifunctional nanospheres that can sensitize multiple aspects of radiotherapy.2S3 + X-ray treatment was half that of X-ray treatment alone. On the other hand, exposed 3-bromopyruvate (3BP) could reduce the overactive oxygen (O2) metabolism of tumor cells and alleviate tumor hypoxia, thereby promoting radiation-induced DNA damage. The combination index (CI) of 3BP and Bi2S3-based RT in Bi2S3-3BP + X-ray was determined to be 0.46 with the fraction affected (fa) was 0.5 via Chou-Talalay’s isobolographic method, which indicated synergistic effect of 3BP and Bi2S3-based RT after integration into Bi2S3-3BP + X-ray. Under the combined effect of 3BP and RT, autophagy was over-activated through starvation-induced and redox homeostasis dysregulation pathways, which in turn exhibited pro-death effects. In addition, the prepared nanospheres possess strong X-ray attenuation and high near-infrared (NIR) optical absorption, thus eliminating the need for additional functional components and could serve as bimodal contrast agents for computed tomography/photoacoustic (CT/PA) imaging.Nanospheres containing high atomic element Bi can effectively absorb ionizing radiation and can be used as radiosensitizers. Cell viability after BiThe rational design of multifunctional nanospheres with the unique properties provided a novel strategy to achieving high therapeutic efficacy in RT. This was accomplished through simultaneous activation of multiple sensitization pathways by increasing ionizing radiation, reducing tumor oxygen consumption, inducing pro-death autophagy, and providing multiple-imaging guidance/monitoring.The online version contains supplementary material available at 10.1186/s12951-023-01970-8. Briefly, the 4T1 cells were seeded at a density of 1 × 105 cells per CLSM dish and incubated for 24 h. Cells were further cultured in fresh RPMI-1640 medium containing FITC-labeled Bi2S3-3BP (Bi: 60 µg mL− 1) and incubated for 0, 1, 2, 3, 4 h. All cells were fixed with 4% formaldehyde (10 min), washed with PBS, and stained with DAPI (15 min) for CLSM observation. Intracellular uptake of Bi2S3-3BP at different time points was also quantified by flow cytometry.The cellular uptake of Bi2S3 (Bi: 60 µg mL− 1), Bi2S3-3BP , 3BP (10 µg mL− 1), Rotenone (10 µg mL− 1), and 2DG (500 µg mL− 1) for 6 h, respectively. Western blot (WB) assay was performed to detect the expression of hexokinase-II (HK-II) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in 4T1 cells after different treatments. Total protein was quantified using the BCA protein quantification kit. The detailed experimental procedure of WB is shown in the supplementary material. Tumor cells were divided into 3 groups (n = 3), and incubated with PBS, Bi2S3 (Bi: 60 µg mL− 1), and Bi2S3-3BP ) for 6 h, respectively. The viability of HK-II, intracellular lactate, and intracellular ATP were measured by the Glucokinase Activity Assay Kit, Lactic Acid Content Test Kit, and the Enhanced ATP Assay Kit according to standard protocols, respectively.Tumor cells cultured in dishes were randomly divided into 6 groups (n = 3), and incubated with PBS, Bi2S3 (Bi: 60 µg mL− 1) or Bi2S3-3BP  for 6 h, the culture vessels were sealed with a sealant to prevent oxygen exchange. The dissolved oxygen in the medium before and after 6 h of the co-incubation was detected using the dissolved oxygen meter . The intracellular hypoxia status was further detected with the ROS-ID® Hypoxia/Oxidative stress detection kit. Typically, cells were seeded in cell-culture dishes at a density of 1 × 105 cells/dish, and cultured overnight. Then cells were cultured in serum-free RPMI-1640 medium containing either Bi2S3 (Bi: 60 µg mL− 1) or Bi2S3-3BP  for another 6 h, and the system was sealed or not sealed with sealant. Cells treated with DFO, a chemical hypoxia inducer, were used as a positive control. All dishes were stained with hypoxia red detection reagent for 30 min. After washing with PBS, the dishes were observed by CLSM.Tumor cells after adherence were incubated with control (untreated), Bi2S3 or Bi2S3-3BP for 6 h, and exposed to X-ray irradiation  was used. Cells/mice were placed 100 cm from the X-ray source. Energy of radiation was 6 MV.). Cell viability was determined by a CCK-8 method. Chou-Talalay’s isobolographic method [2S3-based RT and 3BP on Bi2S3-3BP + X-ray using the equation combination index (CI) = (CBIS(+3BP)/CBIS) + (C3BP(+BIS)/C3BP) + α[(CBIS(+3BP))(C3BP(+BIS))/(CBIS)(C3BP)], where C is the concentration of BIS (Bi2S3 + X-ray) and 3BP (Bi2S3-3BP) alone or in combination (Bi2S3-3BP + X-ray) at a given molar ratio to obtain a given fa. The effect fraction (fa) is the cell death measured by the CCK8 method. Using the more conservative reciprocal assumption (α = 0), CI < 1, CI = 1 and CI > 1 indicate synergistic, additive and antagonistic effects, respectively. For the detection of intracellular ROS generation. Tumor cells cultured in dishes were randomly divided into 5 groups, including control (untreated), X-ray (only), Bi2S3-3BP , Bi2S3 (Bi: 60 µg mL− 1) + X‑ray, and Bi2S3-3BP  + X‑ray. Intracellular ROS generation after different treatments were detected by CLSM after DCFH-DA staining.To estimate cytotoxicity in vitro, 4T1 cells were seeded in 96-well plates, and were cocultured with media containing different concentrations of Bic method  was calc2S3 (Bi: 60 µg mL− 1), and Bi2S3-3BP . All groups received X-ray. Next, fresh RPMI-1640 medium was used to culture cells for additional 7 days. Finally, cells were rinsed with PBS, fixed by 4% paraformaldehyde, and stained with crystal violet about 30 min. Cell colonies were then counted. As for DNA damage assessment by γ‑H2AX immunofluorescence staining, 1 h after X‑ray exposure, the cells were washed with PBS, fixed by 4% formaldehyde, permeabilized with PBS containing 0.5% (v/v) Triton X-100, treated with 5% bovine serum albumin, and incubated with γ‑H2AX  primary antibody at 4 °C overnight. After washing with PBS, cells were incubated with Rhodamine (TRITC)–Conjugated Goat anti-rabbit IgG secondary antibody  at 37 °C for 1 h, and stained with DAPI for CLSM observation. The positive area of DNA damage in every sample was analyzed by ImageJ software.Cloning experiments and DNA damage examination were further conducted under anaerobic and aerobic conditions, respectively. 4T1 cells were seeded into 6-well plates at a density of 6000 cells per well and divided into 3 groups including control (untreated), Bi2S3-3BP , Bi2S3 (Bi: 60 µg mL− 1) + X-ray, and Bi2S3-3BP  + X-ray, respectively. Then 4T1 cells were incubated with MDC  according to the specification for 30 min. After washed by PBS for three times, the autophagosomes dots were monitored by CLSM.Expression of autophagy-related proteins P62 and LC3 was detected by Western blot assay. Besides, immunofluorescence staining was used to detect the formation of LC3 dots. Cytotoxicity of autophagy inhibitor/promoter was detected by CCK-8 kit. The details were described in the supplementary materials. Autophagosomes formed during autophagy were stained with the MDC staining kit, 4T1 cells were seeded in CLSM dishes for 4 groups: Control (untreated), Bi2S3-3BP , Bi2S3 (Bi: 60 µg mL− 1) + X-ray, and Bi2S3-3BP  + X-ray, respectively. Then 4T1 cells were fixed with 2.5% glutaraldehyde for more than 4 h. After washed by PBS for three times, 4T1 cells were fixed by osmium tetroxide for 2 h, dehydrated with graded ethanol and transferred to absolute acetone for 20 min, then embedded in Spurr resin mixture to form ultrathin sections. Finally, the autophagosomes in these cell ultrathin sections were detected by TEM.Autophagosomes were observed more intuitively by TEM, 4T1 cells were treated with Control (untreated), Bi2S3 (Bi: 60 µg mL− 1) + RAPA (3.5 µg mL− 1), Bi2S3 (Bi: 60 µg mL− 1) + 3-MA (6 µg mL− 1), Bi2S3-3BP , Bi2S3-3BP  + RAPA (3.5 µg mL− 1), and Bi2S3-3BP  + 3-MA (6 µg mL− 1), respectively. Cells were incubated with the corresponding nanospheres and drug for 6 h, and then exposed to X-ray. After 12 h incubation, CCK-8 kit were used to detect the cell viabilities.For the detection of cytotoxicity of RT with autophagy inhibitor/promoter, 4T1 cells were seeded in a 96-well plate and treated as follows: Bi2S3-3BP  and saline, oxyhemoglobin saturation  in the tumor at different time points  were determined. Moreover, intertumoral hypoxia status was evaluated by immunofluorescence staining. 4T1 tumor-bearing mice were assigned into 3 groups (6 mice per group) as follows: (1) Control , (2) Bi2S3 , and (3) Bi2S3-3BP . The mice were intravenously injected with corresponding nanospheres. After 6 h of the injection, 3 mice in each group were sacrificed, and the tumor tissues were harvested for hypoxia-inducible factor 1 (HIF-1α) immunofluorescence staining. The other 3 mice in each group were intravenously injected with pimonidazole hydrochloride (60 mg kg− 1) . After almost an hour and a half, tumor tissues were harvested for the detection of Pimonidazole. The fluorescence of HIF-1α and pimonidazole was observed by CLSM and the average fluorescence intensity was analyzed by ImageJ software.Tumor oxyhemoglobin levels were assessed by PA imaging in an oxyhem mode. After post-injection with Bi2S3 , (3) Bi2S3-3BP , (4) X-ray, (5) Bi2S3  + X-ray and (6) Bi2S3-3BP  + X-ray. The mice were intravenously injected with corresponding nanospheres. After 6 h, the mice in X-ray, Bi2S3 + X-ray and Bi2S3-3BP + X-ray groups were exposed to X-ray. Then 3 mice in each group were intravenously injected with DCFH-DA . After 60 min, these mice were sacrificed and tumor tissues were harvested by frozen tumor slides for detecting ROS. Other 3 mice in each group were executed and the tumor tissues were harvested for detecting LC3 (autophagy level) by immunofluorescence staining.In vivo ROS and autophagy levels of tumor tissue after different treatments were evaluated by immunofluorescence staining. 4T1 tumor-bearing mice were assigned into 6 groups (6 mice in each group) as follows: (1) Control , (2) Bi2S3 , (3) Bi2S3-3BP , (4) X-ray, (5) Bi2S3  + X-ray and (6) Bi2S3-3BP  + X-ray. The mice were intravenously injected with the corresponding nanospheres on day 0 and day 4, respectively. Mice in X-ray, Bi2S3 + X-ray, and Bi2S3-3BP + X-ray groups received X-ray irradiations at 6 h after the injection. Their body weight and tumor diameter were recorded every other day during the 14 days of observation. The tumor volumes were calculated as [0.5 × length × (width)2]. On day 14, the mice were sacrificed, and the tumors from each group were harvested and photographed. Tumor tissues from each group were fixed in 4% paraformaldehyde for histological analysis, including hematoxylin & eosin (H&E), proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assays. The mean fluorescence intensity was analyzed by ImageJ software.The tumor-bearing mice were randomly divided into six groups (5 mice in each group) as follows: (1) Control , (2) Bit-test and one-way ANOVA test were used to detect statistical differences between two groups and multiple groups, respectively. p-Values are indicated as n.s. = p > 0.05, *p < 0.05; **p < 0.01; ***p < 0.001, respectively.All data were expressed as mean ± standard deviation (SD). The GraphPad Prism 8.0 software was used for statistical analysis. Two-tailed Student’s 2S3 nanospheres by a facile and effective hydrothermal method, using Bi2O3 as the bismuth precursor. To improve the dispersion and optimize the colloidal stability of Bi2S3 nanospheres, we stably attached mPEG2K-SH to the surface of Bi2S3 nanospheres by rotary evaporation. Next, 3BP was loaded into the pore by magnetic stirring to obtain Bi2S3-3BP  and S2− (160.9 eV), respectively, providing direct evidence for the successful synthesis of Bi2S3 , indicating the successful preparation of Bi2S2 crystals  analysis of nitrogen adsorption-desorption isotherm. Bi2S3 exhibit type-IV isotherms, whose hysteresis curves correspond to mesoporous/microporous structures . The BET specific surface area of Bi2S3 was ~ 30.31 m2g− 1. In addition, the pore size distribution shows that Bi2S3 is dominated by mesoporous pores of 2 to 4 nm . The effective uptake is also substantiated by flow cytometry results   Fig. h-i. Aftesis Fig.  obtained2S3-3BP can effectively alleviate hypoxia in vitro, we next evaluated the effect of Bi2S3-3BP on radiosensitization at the cellular level. In the absence of X-ray irradiation, Bi2S3 did not exhibit any cytotoxicity even when the concentration reached 80 µg mL− 1. X-ray alone exhibited only slight ionizing radiation toxicity, while Bi2S3 + X-ray showed a gradual increase in toxicity with elevated concentrations of Bi2S3, which should be ascribed to the intrinsically enhanced ionizing radiation of Bi. Meanwhile, Bi2S3-3BP exhibited significant cytotoxicity in the absence of radiation, with a cell viability of 42.4%, which could be attributed to the cell growth inhibition of 3BP. In contrast, Bi2S3-3BP + X-ray could further reduce cell activity, with a cell viability of only 11.2%  presented much stronger cell growth inhibition than that of Bi2S3-based RT (Bi2S3 + X-ray), which demonstrated the crucial role of 3BP on RT. To prove the synergistic effect (not only additive effect) of 3BP and Bi2S3-based RT, the CI was calculated. When the influence score (fa) = 0.5, the CI of 3BP and Bi2S3-based RT was 0.46, indicating that 3BP and Bi2S3-based RT had a significant synergistic effect after integrating Bi2S3-3BP + X-ray.The efficacy of RT was positively correlated with oxygen levels, which can prevent repair of DNA damage and thus achieve radiosensitization. After verifying that Bi2S3-3BP + X-ray showed a distinct green fluorescence after X-ray irradiation  than the X-ray-only group (836 clones), indicating that Bi2S3 can effectively sensitize RT. In contrast, the number of colonies in the Bi2S3 + X-ray group (436 clones) was higher under hypoxia than in the normoxic group, suggesting that hypoxia affects the efficacy of RT. The number of cell colonies  was the lowest in the Bi2S3-3BP + X-ray treated group under both normoxic and hypoxia conditions  was higher than that in the Bi2S3-3BP group and Bi2S3 + X-ray group, while the expression of P62 was reduced to 13.8%  and autophagy inhibitors (3-MA). Rapa or 3-MA alone showed almost no cytotoxicity Figure . The CCKagy Fig. g. In con2S3-3BP at the tumor site is essential for subsequent in vivo radiation therapy. Therefore, monitoring the biodistribution of Bi2S3-3BP by real-time imaging is necessary. Considering the excellent NIR optical absorption properties of Bi2S3-3BP, it could act as a PA contrast agent [2S3-3BP  showed almost no change. HIF-1α immunofluorescence staining was also employed to confirm the ability of Bi2S3-3BP to relieve tumor hypoxia in vivo. Extensive red fluorescence was observed in both the saline and Bi2S3 groups, suggesting the intratumoral hypoxia. In contrast, the tumor area exhibited only a faint red fluorescence after intravenous injection of Bi2S3-3BP , Biups Fig. g. Semi-qups Fig. h showed 2S3-3BP + X-ray group showed significantly higher red fluorescence levels than other treatments , Bi2S3 only group, Bi2S3-3BP only group, X-ray only group, Bi2S3 + X-ray group, and Bi2S3-3BP + X-ray group. Nanospheres were intravenously injection into mice on days 0 and 4, with X-ray irradiation administrated to the tumor site at 6 h after the injection   than tumor sections from other groups, indicating severe necrosis of cancer cells. The level of apoptosis observed with TUNEL (green fluorescence) was consistent with that of H&E staining. TUNEL staining showed that Bi2S3-3BP + X-ray group induced more apoptotic cells than the Bi2S3 + X-ray and X-ray only groups. In contrast, the trend was reversed when examining PCNA staining (red fluorescence), which reflects the level of cell proliferation.In addition, H&E, TUNEL, and PCNA staining were performed to test the therapeutic efficacy at a pathological level Fig. g. HE sta2S3 + X-ray group was 3-fold higher than that of Bi2S3-3BP+ X-ray group, while the fluorescence intensity of TUNEL for the Bi2S3 + X-ray was only one-third of Bi2S3-3BP + X-ray group. These results suggest that enhanced RT efficiency was achieved in 4T1 breast cancer tumors when incorporating Bi2S3-3BP nanospheres, as compared with the conventional RT without any sensitization method.Finally, semi-quantitative analysis of apoptotic and proliferative regions Fig. h showed 2S3-3BP nanospheres to effectively sensitize the impact of RT by enhancing ionizing radiation, reducing oxygen consumption and activating pro-death autophagy in tumor cells. These nanospheres are enriched in tumor tissues through the EPR effect, as monitored by CT/PA imaging. The Bi element acted as a radiation therapy sensitizer, effectively absorbing ionizing radiation during RT treatment. Meanwhile, 3BP effectively alleviated the hypoxia status of tumor tissues by inhibiting the tumor glycolytic metabolic pathway and mitochondrial OXPHOS, further aggravating the DNA damage during RT. Additionally, the ROS generation induced by the combined effect of RT and 3BP increased the ROS level. The cellular autophagy induced by the overproduction of intracellular ROS and the starvation effect of 3BP exhibited a pro-death effect, further optimized the final outcome of RT. We compared Bi2S3 + X-ray with Bi2S3-3BP + X-ray under the same experimental conditions, and the cell survival rate of Bi2S3-3BP + X-ray was only a quarter of Bi2S3 + X-ray. Although in vitro effects of different metal nanoparticles in radiation therapy have been observed in previous studies, few studies have combined metal nanomaterials with autophagy. Our study achieved desirable anti-tumor effects at both in vitro and in vivo. It may provide a new idea for the study of nanoradiosensitizers and offer a strategy for a precision radiation oncology approach for clinical tumor radiosensitization.In this study, we successfully designed BiBelow is the link to the electronic supplementary material.Additional file: Fig S1-S2 TEM images of Bi2O3 nanoparticles and Bi2S3 nanospheres. Fig. S3 The porosity of Bi2S3 nanospheres. Fig. S4 Stability of Bi2S3 nanospheres with or without PEG modification in PBS. Fig. S5 The Tyndall effect of Bi2S3 nanospheres in PBS. Fig. S6 (a) UV-vis absorbance spectra of 3BP at various concentrations. (b) The relative absorbance of 3BP at 282 nm against concentration. Fig S7. Cumulative release of 3BP from Bi2S3-3BP. Fig. S8 HK-II viability of 4T1 cells. Fig. S9 Mean Fluorescence intensity quantitative analysis of hypoxia red fluorescence. Fig. S10 Cell viability of 4T1 cells after treat with Rapa and 3-MA. Fig. S11 The recorded PA intensity of Bi2S3-3BP at λ = 700–950 nm. Fig. S12 In vitro PA contrast images and PA values of Bi2S3-3BP at different concentrations. Fig. S13 In vivo PA images of tumors in tumor-bearing mice after intravenously injection of Bi2S3-3BP at different time points. Fig. S14 Changes of PA-signal intensities within tumor regions at corresponding time points. Fig. S15 In vitro CT contrast images and HU values of Bi2S3-3BP at different concentrations. Fig. S16 In vivo CT images of tumor-bearing mice after intravenously injection of Bi2S3-3BP at different time points


Bartonella are generally recognized as zoonotic pathogens of mammals, including many rodent species. However, data on the genetic diversity of Bartonella in some regions are still absent in China. In this study, we collected rodent samples  from Inner Mongolia located in Northern China. The Bartonella were detected and identified by sequencing the gltA, ftsZ, ITS, and groEL genes in them. An overall 47.27% (52/110) positive rate was observed. This may be the first report that M. unguiculatus and E. luteus harbor Bartonella. Phylogenetic and genetic analysis on gltA, ftsZ, ITS, and groEL genes indicated that the strains were divided into seven distinct clades, suggesting the diverse genetic genotypes of Bartonella species in this area. Of those, Clade 5 meets the criteria for identification as a novel species based on gene sequence dissimilarity to known Bartonella species and herein we name it “Candidatus Bartonella mongolica”. Bartonella spp. are emerging zoonotic causative agents distributed worldwide and they pose a significant threat to human health worldwide. In this study, the Bartonella carried by rodents in Inner Mongolia were detected and studied. The high positive rate (47.27%) and the remarkable genetic diversity (seven phylogenetic clades) of Bartonella in rodents indicate that rodent-borne Bartonella may potentially be exposed to local peoples. Bartonella belonging to family Bartonellaceae, order Rhizobiales  represents a group of Gram-negative, facultative intracellular bacteria with worldwide distribution. To date, this genus is composed of at least 53 species, 7 subspecies, and some unnamed Bartonella spp. according to the National Center for Biotechnology Information database [Bartonella species have been recognized as etiologic agents of emerging infectious diseases for both humans and domestic animals. Until 2021, at least 20 Bartonella species have been reported to infect humans [B. bacilliformis transmitted by sandflies is proved to be the agent of Carrion’s disease with high lethality in the absence of adequate treatment [Bartonella species infecting humans, B. quintana is the agent of trench fever mainly representing endocarditis and chronic bacteremia, while B. henselae causes cat scratch disease representing endocarditis, bacillary angiomatosis, and peliosis hepatis [Bartonella species have been described to infect humans, including B. clarridgeiae, B. elizabethae, B. grahamii, B. koehlerae, B. kosoyi, B. melophagi, B. rochalimae, B. tamiae, and B. washoensis, mainly manifesting with symptoms of fever, fatigue, and endocarditis [B. elizabethae, B. grahamii, B. kosoyi, and B. washoensis are all hosted by rodents.The genus database . With threatment . As the  hepatis . In the carditis . Of thosBartonella are mainly transmitted by hematophagous arthropods such as fleas and lice by their bites [Bartonella species have been detected in multiple mammalian hosts including carnivores, rodents, bats, deer, and even marine animals [Bartonella has been reported in rodents, which were considered one of the major reservoir hosts. However, increasing research efforts in bats and other taxa might reveal similarly high diversity [Bartonella infects the erythrocytes and endothelial cells of these animals, and then establishes persistent infections producing bacteremia that may last for months [Bartonella was also observed [Bartonella in nature.Epidemiological studies have demonstrated that ir bites . Bartone animals –19. In tiversity –21. Bartr months . In someobserved . These cBartonella in rodents from China. Up to 2021, multiple Bartonella species have been detected in various provinces including Heilongjiang, Shaanxi, Fujian, Xinjiang, Henan, Zhejiang, Yunnan, Guangdong, Hainan, and Qinghai Provinces, China [2, almost no studies on Bartonella have been performed except for one study reporting Meriones unguiculatus rats harboring Bartonella tribocorum and B. grahamii in this area [Bartonella in China, we collected rodent samples in this region and studied the Bartonella bacteria in them.In recent years, lots of studies have been performed on molecular investigations of s, China –28. Howehis area . To imprThis study protocol was approved by the Ethics Committee of the National Institute for Communicable Disease Control and Prevention, the Chinese CDC , and the General Center for Disease Control and Prevention of the Inner Mongolia Autonomous Region. All the rodents were treated in a humane manner in accordance with the “Rules for Implementation of Laboratory Animal Medicine” from the National Health Commission, China. The studies in this manuscript adhere to the ARRIVE  guidelines for the reporting of animal experiments.Bartonella.In an ongoing plague surveillance project in 2021, rodents were live-trapped using fried food as baits in the desert steppe in three locations  of Siziwang Banner , Ulanqab City, Inner Mongolia Autonomous Region, Northern China. The steel traps (150 mm×80 mm) were produced by Li’s Mousetrap Equipment Manufacturer in Guixi City, Jiangxi Province, China. Traps were checked for rodents each day and cages containing rodents were transported to the lab. After morphological identification , the rodBartonella amplifying a conserved region of the citrate synthase gene (gltA). PCR amplification was performed using a conventional Sensoquest PCR System LabCycler (Germany). Positive and negative controls were set in each PCR run. The PCR parameters are as follows: denaturing at 95°C for three minutes, 40 cycles of 95°C for one minute, 56°C for one minute, and 72°C for one minute. PCR amplification was completed after a final incubation at 72°C for 10 minutes. The PCR products were analyzed by electrophoresis on agarose gel and then observed under UV light. All the PCR products of the expected size (approximately 380 bp) were sent for DNA sequencing. The obtained gltA sequences, which were commonly used for the taxonomic identification of Bartonella species [https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM = blastn&PAGE_TYPE = BlastSearch&LINK_LOC = blasthome) to preliminarily determine their genetic similarity to known species. The DNA of Bartonella sp. we previously detected in Guizhou Province was used as the positive control [2O was used as the negative control.As previously indicated, the primers forward BhCS871.p and reverse BhCS1137.n  were use species , were th control  and ddH2gltA sequences, 23 representative Bartonella strains were selected for further characterization. The cell division protein (ftsZ) gene was amplified using the BaftsZF and BaftsZR primers as shown [groEL) gene, hemi-nested primers were designed in this study  to remove poor quality sequences [The equences . A phyloequences . The besMeriones unguiculatus, 21 Spermophilus dauricus, 21 Eolagurus luteus, and 1 Cricetulus barabensis.From August to September 2021, a total of 110 rodents were collected in suburban areas of three towns  of Siziwang Banner, Ulanqab City, Inner Mongolia Autonomous Region. Morphological identification confirmed the existence of four rodent species: 67 gltA gene (340 bp), a total of 52 rodent samples tested positive for Bartonella: 24 of 67 (35.82%) M. unguiculatus, 10 of 21 (47.62%) S. dauricus, and 18 of 21 (85.71%) E. luteus  is only detected in E. luteus and is closely related to Bartonella grahamii (97.06–97.35% nucleotide similarity), a validated human pathogen [Bartonella krasnovii, with an identity of 98.24%. Clades 5, 6, and 7 are all detected in M. unguiculatus. Clade 5 comprising Strains 35 and 39 is mostly related to Candidatus Bartonella negeviensis, with nucleotide similarity as low as 92.94%. Clade 6  and clade 7  are both closely related to Candidatus Bartonella gerbillinarum, with the highest identities of 96.18% and 97.65%, respectively , ITS (394–526 bp), and groEL (415 bp) genes were successfully obtained from representative strains of all 7 clades , except that the ftsZ and ITS sequences of Clade 1 (strain 18) are unavailable, probably due to the limited universality of primers. Interestingly, phylogenetic trees based on ftsZ and ITS genes are both well consistent with the tree based on the gltA gene , B. grahamii (96.13%), and B. krasnovii (95.74%), respectively. Clades 5, 6, and 7 are all mostly related to B. taylorii, with the highest nucleotide similarities of 87.09%, 86.71%, and 87.55–87.56%, respectively .For the ectively . As to tgroEL sequences showed that the positions of Bartonella strains are obviously inconsistent with gltA, ftsZ, and ITS trees  and clade 7  are dispersed into different lineages. For example, strains 42 and 46 belonging to Clade 6 clustered with strain 48 belonging to clade 7, while strains 28, 34, and 41 (Clade 7) are in the same lineage together with strain 51 belonging to Clade 6. This result may result from several reasons: 1. It is possible that co-infection of different Bartonella strains may present in the rodent blood and the groEL primers may have been more sensitive to a minor variant present; 2. Lack of some important reference sequences in the GenBank Database and in the phylogenetic trees; 3. Possible recombination or mutations of the groEL gene may exist. Clades 3 and 5 are almost unchanged, and they share highest 96.63–97.11% and 94.39–94.63% to B. grahamii and Bartonella vinsonii subsp. arupensis, respectively , the geographical distribution and genetic diversity of rodent-borne Bartonella in many areas are still pending.Bartonella spp. was observed in rodents from Inner Mongolia, with an overall positive rate of 47.27% (52/110). This rate is similar to those previously reported in rodents from Yunnan Province (43.5%) [Bartonella, with the positive rate varying from 35.82%-85.71%. As is currently known, this may be the first report that M. unguiculatus and E. luteus harboring Bartonella, which may expand our knowledge on the host range of Bartonella. Furthermore, the host specificity of Bartonella was also observed in this study. For example, all strains belonging to Clade 3 were detected in E. luteus, which only account for 19.09% (21/110) of the rodent samples. This is well consistent with previous reports that each Bartonella specie only infects one or a few rodent species [M. unguiculatus and S. dauricus are the main hosts of Yersinia pestis, the etiologic agent of plague [Bartonella in these rodents makes it possible that Bartonella spp. may be transmitted to human beings in a similar pathway as plague. Bartonellosis such as cat scratch disease caused by B. henselae has been widely reported in multiple provinces of China, such as Hebei, Fujian, Anhui, Zhejiang, Guangdong, Hubei, Guizhou, and Beijing [Bartonella species were also reported including Bartonella vinsonii subsp. berkhoffii, B. quintana, and B. coopersplainsensis [Bartonella is largely underestimated or ignored.In this study, a high prevalence of  (43.5%)  and Shan (43.5%) . Three o species . Notablyf plague . As thes Beijing . Meanwhiinsensis –44. NoneBartonella was observed, with seven distinct phylogenetic clades identified. Of those, the gltA, ftsZ, ITS, and groEL genes of Clade 5 showed the highest nucleotide identities of 92.94%, 87.09%, 88.89–89.35%, and 94.39–94.64% to reported species. According to the criteria for the definition of Bartonella species [Candidatus Bartonella mongolica”. Genetic and phylogenetic analysis indicated that all the key genes of clade 3 strains are closely related to B. grahamii. Namely, this clade should represent a variant of B. grahamii. As a validated human pathogen, B. grahamii has been reported to cause cat scratch disease, with the symptoms of neuroretinitis and enlarged lymph nodes [B. grahamii in E. luteus and its potential human pathogenicity may suggest the risk of human infection.In this study, remarkable genetic diversity of  species , these rph nodes . The higThis study protocol was approved by the Ethics Committee of the National Institute for Communicable Disease Control and Prevention, the Chinese CDC , and the General Center for Disease Control and Prevention of the Inner Mongolia Autonomous Region. All the rodents were treated in a humane manner in accordance with the “Rules for Implementation of Laboratory Animal Medicine” from the National Health Commission, China.All sequence files are available from the GenBank database (Accession Numbers are shown in S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


In addition, they performed a behavioural go/no-go task outside the scanner. While groups did not differ behaviourally during successful stop trials, the ASD + ADHD group relative to other groups had underactivation in typical performance monitoring regions of bilateral anterior insula/inferior frontal gyrus, right posterior thalamus, and right middle temporal gyrus/hippocampus during failed inhibition, which was associated with increased stop-signal reaction time. In the behavioural go/no-go task, both ADHD groups, with and without ASD, had significantly lower motor inhibition performance compared to TD controls. In conclusion, only young adult males with ASD + ADHD had neurofunctional atypicality in brain regions associated with performance monitoring, while inhibition difficulties on go/no-go task performance was shared with ADHD. The suggests that young people with ASD + ADHD are most severely impaired during motor inhibition tasks compared to ASD and ADHD but do not reflect a combination of the difficulties associated with the pure disorders.Autism spectrum disorder (ASD) often co-occurs with attention-deficit/hyperactivity disorder (ADHD) and people with these conditions have frontostriatal functional atypicality during motor inhibition. We compared the neural and neurocognitive correlates of motor inhibition and performance monitoring in young adult males with “pure” and combined presentations with age-and sex-matched typically developing controls, to explore shared or disorder-specific atypicality. Males aged 20–27 years with typical development (TD;  Approximately 28% of people with autism spectrum disorder (ASD) meet criteria for attention/deficit-hyperactivity disorder (ADHD) . PopulatSuch difficulties of cognitive control in ADHD and ASD, and their neural correlates, are frequently examined using the stop-signal task, which requires withdrawal of already triggered motor responses, and the go/no-go task, which requires selective withholding of prepotent responses . Meta-anChildren and adults with ADHD also demonstrate neurofunctional underactivation relative to typically developing (TD) controls during error or performance monitoring, which is assessed through failed inhibition trials. Underactivation clusters were observed in dorsomedial/ anterior cingulate, left and right inferior and superior frontal regions –23, tempIn ASD, under- and overactivation have been found during cognitive control in frontal brain regions, with medial prefrontal underactivation being the most consistent meta-analytic finding , 26–28, Nevertheless, infrequently controlled co-occurrence of the conditions could have confounded the individual studies and meta-analyses findings in these disorders, which have motivated recent comparisons between “pure” ASD and ADHD groups. Two studies showed that during inhibition, ASD relative to ADHD children and TD controls showed increased right middle frontal gyrus (MFG) activation , and adoA functional magnetic resonance imaging (fMRI) study of motor inhibition and performance monitoring in young adults with ASD and ADHD would be a useful addition to the literature, and elucidate the neural substrates of the high co-occurrence of the disorders in this age group , 3. We tn = 107) aged 20–27 years with ASD, ADHD and ASD + ADHD and typical development. All participants had full-scale IQ (FSIQ) ≥ 70 on the Wechsler Abbreviated Scale of Intelligence-2  = 5.2, p = 0.002), which were higher in ADHD and TD relative to ASD (both ps ≤ 0.012), but not in age or handedness. Groups also differed in self-rated ADHD index  and SDQ hyperactivity domain , which was higher in ADHD and ASD + ADHD, than ASD and TD (ps < 0.001). Informant ratings were in line with self-rated ADHD symptoms in the clinical groups  with all clinical groups being higher than TD (ps < 0.001), although informant ratings showed that ASD + ADHD had higher autistic traits than the ADHD group (p < 0.001). Compared to those included in the analyses, excluded participants had lower IQ, and higher informant ratings of ADHD index and autistic traits, although did not differ in their self-ratings of ADHD and autistic traits , ADHD , and ASD  relative to TD controls . No significant group effects were observe on the secondary measures MRT to Go trials, intrasubject RTV and PERTS , suggesting that the tracking algorithm was successful. There were no differences in the percentage of correctly responded “Go” across groups , which was significantly reduced in ASD + ADHD  and in ADHD , but not in ASD  relative to TD controls , corrected for multiple testing using Tukey-Kramer method. These group differences remained after covarying for IQ, ADHD medication, or any psychotropic medication. No significant group effects were observed on the secondary performance indices  or number of corrected volumes .Groups did not differ in total volume-to-volume head movement , right posterior thalamus/parahippocampal gyrus (PHG)  and in right MTG/hippocampus . A potentially weaker Group effect, although fell short of significance, was found in right AI/STP/IFG . However, since the region was situated the lateral frontostriatal area typically underactivated in ADHD, we still explored pairwise group differences of the extracted averaged beta coefficient of this cluster across groups. The post-hoc analyses indicated that ASD + ADHD had lower activation than the other groups in all four clusters (ps < 0.001 corrected with Tukey-Kramer method), which remained after co-varying for IQ, ADHD medication, or any psychotropic medication.Whole-brain between-group analyses Fig.  revealedNo group effects were found for the contrasts Oddball – Go, and Failed Stop – Successful Stop trials. Within-subject clusters for the contrast Oddball – Go trials are reported in Supplement SBSSRT = −2.14, p = 0.010, 95% CI ), right posterior thalamus/PHG  and in right AI/STP/IFG . The association in right MTG/hippocampus did not meet the corrected p-threshold of significance . No significant association was found between brain activation and PERTS , controlling for diagnostic grouping.Multiple regressions showed selective association between brain activation with reduced SSRT in left AI/STP/MTG/orbital IFG . No significant associations were found between brain activation and those traits and their interactions in the model in which diagnostic grouping were not covaried, particularly in right posterior thalamus/PHG, right AI/STP/IFG and right MTG/hippocampus . A potential weak association between activation in left AI/STP/MTG/orbital IFG and ADHD traits  did not meet the corrected threshold of p = 0.0125. No significant association was found between left AI/STP/MTG/orbital IFG with ASD traits or interactions of traits .No significant associations were found between brain activation and ASD or ADHD traits, and their interactions, while covarying for diagnostic grouping in all four regions  –54, mediPerformance monitoring during a stop-signal task consists of both conflict monitoring or withholding in the earlier Go process in case a Stop signal appears; and a later error processing to modify behaviour during failed stopping . BehavioInterestingly, the brain activation was neither specifically associated with traits of ASD or ADHD, beyond the variation accounted already by diagnostic grouping or otherwise. A weak association between activation in one performance monitoring cluster in left AI/STP/MTG/orbital IFG with reduced ADHD traits was in the expected direction but did not meet the corrected threshold of significance. Taken together, the atypicality of brain activation tested in this manner appears more strongly associated with cognitive task performance, and less directly associated with the symptom severity of the diagnoses per se, which is in keeping with findings of the separability of cognitive difficulties from core diagnostic symptoms as shown in ADHD research .In addition to the brain activation finding, difficulties of response withholding were also observed during the go/no-go task in the ASD + ADHD and in ADHD groups, with large effect sizes, relative to TD controls. While not significant statistically, both ADHD groups also demonstrated a pattern of increased mean SSRT relative to TD controls. Together these findings suggest that motor inhibition difficulties are primarily associated with ADHD diagnosis, which is in line with evidence from several behavioural studies showing increased difficulties of cognitive control or motor inhibition problems in ASD + ADHD relative to ASD alone , 62, 63,The non-significant group differences in SSRT and the shared response withholding difficulties primarily in ADHD and ASD + ADHD during the go/no-go task, suggest a similarity between the two groups. However, the added presence of right IFG/AI and midbrain/limbic underactivation during error monitoring in ASD + ADHD suggested more severe neurofunctional atypicality in the combined group overall. A similar conclusion has been drawn previously in ASD + ADHD children and adolescents during an fMRI delay-discounting task . NotablyThe altogether absence of the hypothesised functional underactivation clusters in ADHD, while unexpected, is in line with a number of fMRI inhibition studies in ADHD adults , 65–67. This study was constrained by some methodological limitations, including its relatively small sample size despite, to our knowledge, being the largest comparative fMRI study of motor inhibition in ASD and ADHD to date and the only one to compare the ASD + ADHD with the pure groups in young adulthood , 32. TheThe increased sample homogeneity afforded by including young adult males only, selected due to the high prevalence of ASD and ADHD among males , 75, wasTo conclude, this study shows that young adult males with ASD + ADHD, but not those with ADHD alone, had underactivation in inferior fronto-insular-thalamic regions, reflecting earlier processes of inhibitory withholding during performance monitoring. On behavioural task, both ADHD groups with and without ASD were impaired in selective motor action withholding. Together the findings suggest that among young adults, those with ASD + ADHD have the most severe cognitive and neurofunctional atypicality, which do not appear to be a combination of the pure disorder forms.Online supplementary materials